Tag Archives: treatment

Oxytocin is not a viable treatment for children and teenagers with autism, after all

New research reports that oxytocin, despite the hopes pinned on it by many, does not produce any signs of helping children with autism improve their social abilities.

Image credits Jesper Sehested / Flickr.

Oxytocin is a naturally occurring hormone, and an important neurotransmitter (brain messenger molecule). It is more commonly known as the ‘love hormone’, is released by the pituitary gland, and seems to play a pivotal part in helping us bond socially and/or with our children. There has also been research that implicated oxytocin in the emergence of autism; the emergence of this disorder seemed to be correlated to a mutation on the oxytocin receptor gene (OXTR).

However, this link does not seem to hold up to scrutiny. Despite mixed results in regards to oxytocin’s outcomes in improving social skills in children with autism in previous experiments, new research casts doubt on its potential. Although disappointing, such data will hopefully guide our attention to other, more promising candidate treatments.

Not the one

“There was a great deal of hope this drug would be effective,” said the study’s principal investigator and lead author, Linmarie Sikich, M.D., associate consulting professor in the Department of Psychiatry & Behavioral Sciences at Duke University School of Medicine. “All of us on the study team were hugely disappointed, but oxytocin does not appear to change social function of people with autism.”

Medically, oxytocin is administered mainly to help induce labor. But we do know that it functions as a neurotransmitter and, due to its effects on the workings of the brain, has been proposed as a treatment for autism. There was some evidence to back up this proposal, but it was inconsequential: some studies found it effective at the task, others reported it showed no benefit. Against this backdrop, Sikich’s team set out to determine whether this hormone could have practical applications in the treatment of the disorder or not.

They worked with 290 children ages 3-17, which they separated into groups based on how severe their autism symptoms were. All children were then randomly assigned to equal-sized groups and received either oxytocin or a placebo, via daily nasal sprays, over a period of 24 weeks.

Each child underwent screenings and assessments of their social abilities at the start of the trial to establish a baseline. These were repeated at the midpoint and end of the trial, to track their progress (i.e. the effectiveness of the oxytocin regimen in improving their symptoms). In addition to these, the researchers and the children’s parents also provided assessments using standard analytic tools for autism.

Overall, the authors explain that the oxytocin was well tolerated by the children and had few to no side effects. That being said, it didn’t produce any meaningful effect in those who received oxytocin over those who were administered a placebo. Given that this is one of the largest studies looking into the effectiveness of the hormone in the treatment of autism, such findings do not bode well for its future as a treatment option.

“Thousands of children with autism spectrum disorder were prescribed intranasal oxytocin before it was adequately tested,” says senior author Jeremy Veenstra-VanderWeele, M.D., of New York State Psychiatric Institute and Columbia University. “Thankfully, our data show that it is safe.”

“Unfortunately, it is no better than placebo when used daily for months. These results indicate that clinicians and families should insist that there is strong evidence for the safety and benefit of new treatments before they are provided to patients in the clinic.”

The team concludes, based on these findings, that there simply isn’t enough evidence of oxytocin having any effect in this role. They add that there’s too little here to even justify further research into its potential for treating autism spectrum disorders and that we should focus on more promising candidates instead.

Autism has taken up a large public interest in the last few years, maybe a decade or so. Personally, I think that part of this effect was caused by fear-mongering misinformation regarding vaccines (the famous ‘vaccines cause autism’ slogan). First off, I’d like to point out that autism itself is not as prevalent as we’ve been led to believe. Statistics do reveal broader trends than we’d be able to see using other means, but it can only be as effective and clear as the data we have on hand.

Still, for those whose loved ones might be on the spectrum, news such as this can definitely feel disheartening. I’d like to remind those of you who may be in such a position that autism is in no way a sentence to a bad life or to being shunned socially. Neurodivergent individuals can and do become valued, respected, and loved members of their social groups and wider societies. Their often unique skill sets and predispositions have been recognized and valued all throughout history.

There are certainly unique challenges that people with autism have to contend with. I have seen this through my own personal experiences with those who fall somewhere on the spectrum. Social skills can definitely be one of those more problematic areas. But I have also seen those who managed to overcome these issues, work around them, or find a way forward that makes them happy even without developing ‘normal’ social skills.

A treatment for autism would definitely be welcomed for those who desire it. But not having such treatment at hand is in no way a cause for despair. If you or someone you care for has to contend with autism, know that it is not a flaw that requires fixing. To be human is to be imperfect, and the measure of our lives is given by how well we can find happiness even through such imperfections.

The paper “Intranasal Oxytocin in Children and Adolescents with Autism Spectrum Disorder” has been published in the New England Journal of Medicine.

Plasmodium vivax.

Novel anti-malaria drug can flush the parasite out of hiding with a single pill

Known as tafenoquine, the new drug was developed by GlaxoSmithKline (GSK). After receiving FDA approval, the drug also has to pass the scrutiny of other national drug regulation agencies before it can see global use.

Plasmodium vivax.

Stained micrograph showing a mature Plasmodium vivax trophozoite (the purple blotch in the middle).
Image credits CDC / Steven Glenn, Laboratory & Consultation Division.

The compound is tailored to fight the recurring form of malaria. This disease, caused by the parasite Plasmodium vivax and estimated to infect over 8 million people each year, is especially tricky to cure as the parasite can hide in the host’s liver and emerge many times over a period of years.

Persistent malaria

The recurring form of the disease is the most commonly encountered type of malaria outside of Sub-Saharan Africa. Children are particularly hard-hit by the disease. A single bite from a malaria-infected mosquito will cause several bouts of the disease, which means a lot of missed school and progressively-poorer health during formative years.

Even worse, infected individuals act as unwilling spreaders of the disease. If the parasite reawakens and passes through to their blood, any mosquito that bites them will spread malaria to other people. This combination of a dormant state and high infectivity make recurring malaria especially hard to eliminate.

Still, with the FDA’s recent approval of tafenoquine, that state of affairs may change. The drug can flush the parasite out of its dormant state in the liver, preventing it from re-infecting its host. Even better, tafenoquine doesn’t interfere with other drugs used to treat the immediate infection caused by the parasite, so both treatments can be taken side-by-side.

We already have a drug on hand to clear the plasmodium out of the liver — it’s called primaquine. However, primaquine treatment needs to be followed for 14 days at a time, while the tafenoquine course only involves taking a single dose.

There’s a legitimate concern in the medical community that many patients with recurring malaria feel better after a few days of primaquine treatment and don’t follow the course to its completion — which isn’t nearly enough to flush out all the parasites.

While the FDA approval of the drug vouches for its effectiveness, the administration warns that the drug comes with side effects you should be aware of.

First and foremost, people suffering from enzyme G6PD deficiency should not take the drug, as it can cause severe anemia. The FDA recommends that patients are screened for this deficiency before being given the treatment — but this may be virtually impossible in the poorer areas where malaria is most common. Secondly, there are concerns that higher doses may interact with pre-existing psychiatric conditions.

Despite its potential risks, the drug could help reduce the incidence of Plasmodium vivax malaria on a global level, however.

“The approval of Krintafel [the brand name for tafenoquine], the first new treatment for Plasmodium vivax malaria in over 60 years, is a significant milestone for people living with this type of relapsing malaria,” says Dr Hal Barron, president of research and development at GSK. “Together with our partner, Medicines for Malaria Venture, we believe Krintafel will be an important medicine for patients with malaria and contribute to the ongoing effort to eradicate this disease.”

The next step will be for the drug to be assessed by regulators in countries where this form of malaria is a significant problem.

FDA approves first Ebola treatment

Illustration of the Ebola virus.

Over 2 years since the Kivu Ebola epidemic began in August 2018, the US Food and Drug Administration (FDA) approved the first antibody cocktail for the treatment for Zaire ebolavirus (Ebola virus) infection in adult and pediatric patients.

The drug, called Inmazeb, was developed by Regeneron — a biotech company also testing an antibody treatment for COVID-19. In clinical trials, patients who took Inmazeb were far less likely to die from Ebola virus disease.

In the clinical trial conducted during the outbreak in the North Kivu region, those treated with Inzameb experienced 33.5% mortality after 28 days. The World Health Organization (WHO) reports the virus’ mortality rate can be as high as 90%, depending on the outbreak.

The PALM trial, Pamoja Tulinde Maisha (meaning “together save lives”), is a randomized, controlled trial of four investigational agents (ZMapp, remdesivir, mAb114, and REGN-EB3, now called Inmazeb) for the treatment of patients with Ebola virus disease.

To help control the Ebola virus outbreak, Inmazeb is being administered for free in the DRC with the support of the Biomedical Advanced Research and Development Authority (BARDA), and Regeneron has stated that it is working with non-governmental organizations and public health agencies to make sure the treatment is accessible to low- and middle-income countries.

This trial and other studies done during Ebola outbreaks over the past decade showed that it was possible and operationally feasible to conduct scientific research during an epidemic. Researchers are now applying those lessons during the COVID-19 pandemic. One of the US-based trials for the antiviral remdesivir, which the FDA authorized for emergency use, was modeled after the PALM trial.

“Today’s approval highlights the importance of international collaboration in the fight against Ebola virus,” said John Farley, MD, MPH, director of the Office of Infectious Diseases in the FDA’s Center for Drug Evaluation and Research, in a press release.

National Geographic | Should be updated to say Ebola is now treatable & vaccine-preventable

Zaire ebolavirus, commonly known as Ebola virus, is one of four Ebolavirus species that can cause a potentially fatal human disease. Ebola virus is transmitted through direct contact with blood, body fluids and tissues of infected people or wild animals, as well as with surfaces and materials, such as bedding and clothing, contaminated with these fluids. Individuals who provide care for people with Ebola virus, including health care workers who do not use correct infection control precautions, are at the highest risk for infection. Ervebo, the first vaccine for the prevention of Ebola was approved by the European Medicines Agency in October 2019 and the US FDA in December 2019.

This protein explains why you get acne — and may offer a new way to cure it

Credit: Pixabay.

The lack of expression of a certain protein in the skin is associated with acne, according to a new study published today in Nature Communications. According to the authors, new treatments that promote the growth of this newly significant protein could be developed as a result of the research.

New insights into acne reveal potential treatment targets

Acne is arguably the most common skin condition in the world, affecting at any time about 650 million people. The skin disease typically occurs when oil glands become clogged, forming spots, pimples, and sometimes cysts. However, there are still many unknowns about acne formation.

“Although acne is one of the most common dermatological conditions, its pathogenesis remains incompletely understood,” Dr. Christina Philippeos, Research Associate in the Centre for Stem Cells & Regenerative Medicine at King’s College London, told ZME Science.

To learn more about acne, Philippeos and colleagues investigated whether GATA6 (GATA-binding protein 6), a protein expressed in the hair follicle, might be involved in any way. There were some hints that it is.

Previously, another group showed that when this protein is switched off in epidermal cells that line the pilosebaceous unit (a structure that consists of the hair follicle and sebaceous glands), lesions would form filled with acne-like material.

To learn more, the researchers examined skin biopsies from five healthy volunteers and nine patients with different degrees of acne severity. Upon examination, they found that healthy people had high levels of GATA6 while acne cases had reduced GATA6 levels.

Back in the lab, the researchers developed a human sebaceous organoid model that ultimately showed that GATA6 is involved in several physiological processes that regulate the upper pilosebaceous unit (PSU). One such process has to do with the production and differentiation of keratinocytes, which are the primary, most common cells found in the outermost layer of the skin.

“Acne is a disease specific to humans and no animal model recapitulates its pathological features fully. Therefore, acne research has relied heavily on translational histopathological studies and cell-based studies. It can be quite a challenge to show that the findings seen in vitro are representative of the disease in humans. Moreover, accessing histological samples of acne skin is difficult, as this requires patient biopsies, usually performed on the face. Nevertheless, we really enjoyed the technical challenge of creating small sebaceous 3D organoids and isolating hair follicles from fresh human skin (obtained from plastic surgery waste) to create in vitro mini-organ cultures to silence GATA6 in these PSUs,” Philippeos told ZME Science.

What’s more, GATA6 modulates immunological signals that contribute to the inflammatory pathways seen in acne and may also prevent the formation of clogged pores.

But perhaps most importantly, the researchers found that the expression of GATA6 was induced by retinoic acid, a product that is used in some acne treatments.

“Our study shows that isotretinoin partially works through GATA6 induction. Therefore, there is already a GATA6 based treatment! But our study is still in the discovery science phase. GATA6 has never been implicated in acne pathogenesis before. Further research is needed to identify which compounds may specifically stimulate GATA6 expression in acne patients, before treatment may go to trial,” Philippeos said.

In the future, the researchers plan on doing more research into the role of GATA6 in the human skin. Meanwhile, Philippeos recommends systemic isotretinoin to treat acne, which she refers to as the “current gold standard treatment” but which also has multiple side effects.

“This study shows the public that the development of acne is a complex, multifactorial process. It is still not fully understood, but this finding sheds more light on these processes, which could open up new avenues for the research and treatment of this disease,” she concludes.

A protein in our pancreas and lungs could help treat asthma

Research using animal models and human tissue samples found a new potential avenue of treatment for asthma and chronic obstructive pulmonary disease (COPD).

Human alveolar tissue seen under the microscope.
Image credits Yale Rosen / Flickr.

An international research team reports that activation of a protein called free fatty acid receptor 4 (FFA4) in lung tissue can help reverse hallmark symptoms of asthma such as inflammation and obstruction of the airways in patients resistant to current treatments.

While the effect has not yet been confirmed in living human patients, the results warrant continued research into drugs that can target and interact with this protein, say the authors.

A breath of fresh air

“By the identification of this new mechanism we offer the hope for new effective medicines for those patients that are not responsive to our current treatments,” says Professor Christopher Brightling, an author on the paper from the University of Leicester.

The study identifies an existing class of medication that can interact with the FFA4 protein in model animals and human tissue samples to address the condition. FFA4 is found in cells in the gut and pancreas and helps to control blood glucose levels. Dietary fats, most notably omega 3 oils from fish, are known to activate this protein.

First, the team found that this protein is also present in lung tissues, which they called “surprising”. Furthermore, they found that activating FFA4 in mouse lung tissue causes smooth muscle surrounding the airways to relax, allowing more air to flow in. This effect also worked to reduce inflammation caused by exposure to pollution, cigarette smoke, or allergens. Cells in human lung tissue reacted in a similar way, they add.

Because this mechanism is different from the ones used for current asthma and COPD medication, it could prove to be an effective avenue of treatment for unresponsive or severe cases.

“It was indeed a surprise to find that by targeting a protein — which up to now has been thought of as being activated by fish oils in our diet — we were able to relax airway muscle and prevent inflammation,” says Andrew Tobin, Professor of Molecular Pharmacology at the University of Glasgow. “We are optimistic that we can extend our findings and develop a new drug treatment of asthma and COPD.”

With air pollution reaching worrying levels across the world, asthmatic patients are likely to see worsening symptoms. Such medication could help complement our current treatments to help preserve their health and quality of life.

The paper, “Pathophysiological regulation of lung function by the free fatty acid receptor FFA4,” has been published in the journal Science Translational Medicine.

Human SARS antibody could pave the way towards a COVID-19 cure

An antibody isolated from a SARS (Severe Acute Respiratory Syndrome) survivor after the 2003 epidemic could pave the way towards a treatment for COVID-19.

Stock image.
Image credits Michal Jarmoluk.

The antibody, named S309, is currently “on a fast-track development and testing path” with California-based Vir Biotechnology. according to a press release. Preliminary findings, published in a study in the journal Nature, suggest that the antibody should be effective against several members of the coronavirus family, including the strain responsible for the current pandemic.

New virus, old tricks

“Right now there are no approved tools or licensed therapeutics proven to fight against the coronavirus that causes COVID-19,” says David Veesler, assistant professor of biochemistry at the University of Washington School of Medicine and lead author of the study. He adds that “we still need to show that this antibody is protective in living systems, which has not yet been done.”

The antibody works against the SARS virus by chemically binding to its spike proteins (the structures that look like ‘spikes’ on the virus’ surface). These are crucial for the mechanisms the virus uses to perceive, access, and infect human cells. By blocking them, the antibody effectively destroys its ability to cause illness.

However, one finding of the study points the way to an exciting possibility: that S309 can also neutralize SARS-CoV-2, the coronavirus responsible for the current outbreak, as well as other strains in its extended family.

First, the team isolated several monoclonal antibodies from the B-type lymphocytes (white blood cells) of a person who got infected and then recovered during the SARS epidemic of 2003. Although these antibodies were tailored to fight another virus, it was for one closely related to the coronavirus, making it likely that they would also interact with it.

Type B lymphocytes form some of the immune system’s ‘memory cells’. Memory cell surfaces are littered with protein receptors that bind to antigens (molecules that give away the presence of an infection) of pathogens the body has fought off in the past. Once this reaction takes place, they direct the body to start producing appropriate antibodies.

Through the use of cryo-electron microscopy studies and binding assays, the team found that the S309 antibody binds to a spike protein that is identical across many lineages of the coronavirus family. This protein is also a critical part of its ability to infect cells, so it’s very unlikely that it would suffer mutations over time. Even better, it’s identical across many coronaviruses the team investigated — meaning it could fight all of those strains.

While the S309 antibody was particularly good at this task, it wasn’t the only useful one. Other antibodies isolated from the patient could also bind to the spike protein, although not as strongly. The authors say a mix of all these antibodies would form the basis of the new treatment. This way, they can support each other’s activity and ensure the highest level of protection possible across multiple strains and in the face of any mutation of the spike proteins, however unlikely.

The treatment could be used to prevent infection in people at high risk of exposure, but it doesn’t work as a vaccine — it would offer protection only for a limited time. Alternatively, it can be applied as therapy for severe cases of COVID-19 in patients who are already infected.

The paper “Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody” has been published in the journal Nature.

A potential treatment against COVID-19 developed from llama antibodies against SARS

A llama named Winter might have given us a treatment against the coronavirus.

Stock Image via Pixabay.

A team of researchers from The University of Texas at Austin, and the National Institutes of Health and Ghent University, Belgium, report developing a potential treatment for COVID-19 by combining two antibody molecules produced by llamas. Because of the small structure of this molecule, it’s probable that it can be administered via an inhaler, allowing it to be administered directly at the site of infection.

Initial testing showed that the compound is effective at blocking the virus’ ability to infect cells in culture. Despite the encouraging results, the treatment still needs to undergo pre-clinical and clinical trials. The study is currently in a preprint format and will be published in the journal Cell on May 5th here.

No-outbreak llama

“This is one of the first antibodies known to neutralize SARS-CoV-2,” said Jason McLellan, Associate Professor of Molecular Biosciences at UT Austin and co-senior author, referring to the virus that causes COVID-19.

The research draws its roots in previous work performed by the team after the SARS and MERS outbreaks in 2016. They were investigating whether a potential vaccine could be designed against these pathogens in llamas, which they injected with stabilized spike proteins recovered from the viruses. These proteins are the biochemical mechanisms that allow the virus to infect human cells.

Llamas, and the camelid family they belong to, produce two kinds of antibodies — one that’s similar to human antibodies, and one that’s about a quarter of the size of ours. The antibodies used in this study were isolated from a llama named Winter, which was about 9 months old at the time.

The smaller antibody molecule that was effective against the SARS virus was able to bind to the SARS-CoV-2 virus, the one responsible for the COVID-19 outbreak, but only “weakly”. However, by merging two of these together, the team created the current treatment. In cell cultures, it showed great effectiveness in blocking the virus’ ability to infect cells. In essence, it chemically ties to the proteins the coronavirus uses to pass through cell membranes and doesn’t let go — so the virus can’t use those proteins any longer.

The team is now preparing for preclinical studies; if everything goes well, the treatment will enter clinical testing (on humans). Just like every other drug, it won’t be approved for use until it passes both of these steps and is deemed safe.

Vaccines against the disease understandably get a lot of attention these days, but this isn’t a vaccine — it’s a treatment. Vaccines are administered in order to train our immune systems against different viruses and start conferring natural protection one or two months after use. Treatment can be used to directly address (or prevent) infection instantly, so, if approved for use, it could be employed to treat patients who are already showing symptoms.

“Vaccines have to be given a month or two before infection to provide protection,” McLellan said. “With antibody therapies, you’re directly giving somebody the protective antibodies and so, immediately after treatment, they should be protected. The antibodies could also be used to treat somebody who is already sick to lessen the severity of the disease.”

Such a treatment would be useful for at-risk groups, such as the elderly (who also show a relatively modest response to vaccinations) and workers who have a high risk of exposure such as healthcare workers. The ability to administer this treatment via an inhaler also makes it ” potentially really interesting as a drug for a respiratory pathogen because you’re delivering it right to the site of infection,” said Daniel Wrapp, a graduate student in McLellan’s lab and co-first author of the study.

How to care for someone with COVID-19 while living in the same household

The novel coronavirus is extremely contagious and its effects on the body can be unpredictable. However, most cases are mild and patients can easily recover while staying home. But this begs to question: how do you safely manage treatment if you live with other people in the same household?

It might sound like it’s unavoidable to get sick if your spouse or roommate is confirmed positive, but that’s not necessarily true as long as you diligently adhere to some precautions.

“If you have somebody at home who has symptomatic COVID-19, you want to treat the room that they stay in, in a sense, like a hospital room. What does that mean? Limited incursions or excursions, in or out, of that room. That person is quarantined in that room, ideally with a window open. You have to treat that room as infected,” Dr. Gregory Poland, a Mayo Clinic COVID-19 expert, said in a statement for the Mayo Clinic News Network.

According to studies and data reviewed by Poland, the transmission rate of the coronavirus is as low as 10% and as high as 60%. Obviously, when you live in the same home as an infected person, the risk goes up dramatically due to sheer daily exposure. But there are things you can do to limit that exposure and the aforementioned risk.

The patient should be isolated in their own room for at least 14 days, even after symptoms subside. During this time, the patient should wear a mask each time they come outside their room. Any surfaces that came in direct contact (physical touch) with the patient should be thoroughly disinfected.

Hand-washing is extremely important at this point, which family members should practice frequently. Family meals should not be taken together with whoever is ill.

Although there is limited evidence that animals can get ill with COVID-19, it hasn’t been ruled out. For this reason, cats, dogs, and other pets should be isolated from the patient.

Concerning treatment at home, there’s not very much you can do other than making sure the patient is well hydrated and rested until the illness subsides by itself. There is no approved antiviral medication yet for COVID-19.

Besides being careful not to get infected themselves, people caring for COVID-19 patients in the same household should also monitor for worsening symptoms. Some emergency signs include troubled breathing, chest pain, and bluish lips or face. If symptoms become concerning, household members should immediately contact a medical care provider.


Mini liver.

First lab-grown mini livers will allow researchers to study the organ, its diseases, and treatments

Researchers at the University of Pittsburgh (Pitt) School of Medicine have successfully grown miniature human livers in the lab.

Mini liver.

Photograph of rat liver, stripped of rat-specific cells and re-seeded with engineered human liver cells.
Image credits UPMC.

The genetically-modified diminutive organs are meant to be a test platform for scientists to simulate human liver disease progression and test therapies on. As a proof of concept, the Pitt team created one such miniliver that mimics non-alcoholic fatty liver disease (NAFLD).

DeLivering on demand

“This is the first time we can create genetically engineered human mini livers with a disease using stem cells in the lab,” said senior author Alejandro Soto-Gutierrez, Ph.D. and associate professor of pathology at Pitt’s School of Medicine.

The team creates their tiny livers by genetically-engineering human skin cells. These cells are programmed to simulate a certain disease, are then reverted back to their stem state, and then made to mature into fully-functional liver cells.

For the current paper, the team modified the cells to express a chemically activated switch that could clamp down the on SIRT1 gene (SIRT1 proteins are commonly associated with NAFLD). After turning these cells into liver cells, the researchers seeded them into rat livers (which were previously stripped of their own cells). The implanted cells matured into functional 3-D mini livers, with the blood vessels and other structural features of a normal organ.

The organ mimics non-alcoholic fatty liver disease (NAFLD), a condition which can lead to cirrhosis or even liver failure. NAFLD is quickly becoming the leading cause of chronic liver disease in the United States due to its association with obesity.

The team says that their mini livers offer researchers a unique platform to understand not just a disease and how it progresses, but also for the testing of therapeutics. It’s common for drugs to fail in clinical trials despite promising results in mice, they explain, citing the drug Resveratrol. Resveratrol acts on SIRT1, and it was effective in mouse models for the treatment of NAFLD but failed in human clinical trials.

“Mice aren’t humans,” Soto-Gutierrez said. “We are born with certain mutations, polymorphisms, that will predispose us to certain diseases, but you can’t study polymorphisms in mice, so making a mini customized human liver is advantageous.”

What sets the mini livers apart from ‘organoid‘ cultures — bundles of cells that self-assemble into simple versions of organs — is the presence of those structural features such as blood vessels, the team explains. However, they caution that the mini livers “lack the distinct zones of metabolic function” that normal livers have.

Once they fully matured, the team flipped the genetic switch they programmed into the cells (to suppress the SIRT1 gene) and the mini livers started to mimic the metabolic dysfunction observed in tissues NAFLD patients. Just like in the clinical trials, Resveratrol wasn’t effective on these livers, either.

However, the mini livers did allow the team to figure out what went wrong. Resveratrol boosts the activity of SIRT1 proteins not SIRT1 genes. When SIRT1 gene expression is suppressed, such as is the case with the micro livers and perhaps also NAFLD patients, there isn’t any protein to act on. The drug doesn’t work because it’s targeting the wrong step.

“That’s an insight that could only come from studying functional human tissue,” Soto-Gutierrez said.

“I imagine in the future we can make human livers where you can order what kind of function you want, or even enhance function.”

However, we’re a long way away from that point. These mini livers won’t be ready for clinical applications like transplantation anytime soon, Soto-Gutierrez adds.

The paper “Generation of Human Fatty Livers Using Custom-Engineered Induced Pluripotent Stem Cells with Modifiable SIRT1 Metabolism” has been published in the journal Cell Metabolism.

MS army photo.

The worst of multiple sclerosis can be avoided or delayed with early treatment

Against multiple sclerosis, early treatment is key.

MS army photo.

Image credits U.S. Air Force / Staff Sgt. Alexandre Montes.

A new study led by researchers from the Royal Melbourne Hospital and the University of Melbourne found that early treatment — particularly within five years of onset — is effective in delaying the progress of multiple sclerosis (MS). Such measures can delay progress to the second stage of the disease, which is characterized by progressive levels of physical and mental disability.

The study is the first to provide evidence that currently-available treatments can delay the progress of MS.

Preventive measures

The study used data from 1555 patients from 68 neurological clinics across 21 countries. Tomas Kalincik, Associate professor at the University of Melbourne and study co-lead author, says that the findings showcase how important proactive treatment is in dealing with MS. The research focused on patients with relapsing-remitting MS commencing or clinical monitoring between 1988-2012 with minimum 4 years’ follow-up.

“People who converted from relapsing MS to secondary progressive MS experience gradual and mostly irreversible worsening of disability,” he explained.

“Most of the therapies that we use to treat MS have no effect once people have converted to secondary progressive MS.”

Currently, more than 23,000 Australians are living with MS, the paper explains. The conversion to the secondary progressive stage of MS is characterized by worsening of physical and mental capacity. The team, therefore, argues that preventive treatment is a very powerful tool in improving the quality of life for MS patients.

“This study shows that the therapies they have been treated with for many years, significantly improve the quality of their lives over the long-term,” Kalincik said.

Patients included in the study that underwent “initial treatment with fingolimod, natalizumab, or alemtuzumab” had a reduced risk of developing second-stage MS over a 5-year period. All drugs studied here showed different results, although all were effective. For example, patients initially treated with glatiramer acetate or interferon beta had a 12% chance of conversion to secondary MS, compared to 27% for the control group. Early fingolimod treatment reduced this risk to 7% compared to 32% for controls, and natalizumab to 19% compared to 38% for controls.

Kalincik said he hopes the results will reassure both neurologists and patients with MS that the disease can be managed, and the worst of it avoided — if treatment is started in time. The findings should also help point to the optimal path for treatment, the study adds.

The paper “Association of Initial Disease-Modifying Therapy With Later Conversion to Secondary Progressive Multiple Sclerosis” has been published in the Journal of the American Medical Association.

After millions of tests, researchers find the most promising compounds against malaria

Researchers have isolated the most promising compounds for dealing with malaria.

Elizabeth Winzeler, PhD (right), and her malaria research team at UC San Diego School of Medicine (UCSD). Image credits: UCSD.

There have been 219 million malaria cases in 2017, and the number is on the rise, according to the World Health Organization. The disease has killed over 400,000 people last year alone, and prevention and treatment methods remain difficult to implement at a large scale.

“It’s difficult for many people to consistently sleep under mosquito nets or take a daily pill,” says Elizabeth Winzeler, PhD, professor of pharmacology and drug discovery at University of California San Diego School of Medicine. “We’ve developed many other options for things like birth control. Why not malaria? The malaria research community has always been particularly collaborative and willing to share data and resources, and that makes me optimistic that we’ll soon get there too.”

Most malaria drugs focus on treating the symptoms of the disease once it has infected the body. Not only is this not doing all that much to prevent the infection spread, but the parasite is also starting to develop drug resistance to several treatments.

“In many ways, the search for new malaria drugs has been a search for something akin to aspirin — it makes you feel better but doesn’t necessarily go after the root of problem,” Winzeler adds.

[panel style=”panel-danger” title=”Plasmodium” footer=””]Malaria is caused by a single-celled parasite called Plasmodium, which is neither a virus nor a bacteria. Plasmodium multiplies in red blood cells of humans as well as in the mosquito intestine and is spread by the Cules and Anopheles mosquitoes.[/panel]

Extracting sporozoites of the malaria parasite from mosquitoes in Elizabeth Winzeler’s lab. Image credits: UCSD.

In a study recently published in Science, Winzeler and colleagues took a different approach: they spent two years extracting various strains of malaria parasites and systematically exposed them to over 500,000 chemical compounds to see what works best against them. After millions of tests, they selected the 631 most promising ones.

Their aim is to tackle malaria at an early stage, before the infection sets out through the body. Essentially, when the female mosquito feeds on an infected person, both male and female forms of the parasite are ingested along with human blood. The male and female forms of the parasite meet and mate in the mosquito’s gut and are passed to another human who is bitten by the same mosquito. However, before the parasite starts to multiply in the bloodstream and make people sick, it infects the liver — this is where researchers want to strike.

As you’d expect, testing all of these compounds took a long time — a really long time.

“In a good week, we’d be able to test 20,000 compounds,” Winzeler said, “but of course many of the mosquitoes we received would be dried out, frozen or covered in fungus.”

It was a painstaking work, but after all of this, researchers successfully identified the promising compounds. Even better, they decided to not patent any of these compounds. Instead, they’re making it available to all interested groups for further research.

“It’s our hope that, since we’re not patenting these compounds, many other researchers around the world will take this information and use it in their own labs and countries to drive antimalarial drug development forward,” Winzeler said.

In the meantime, Winzeler and colleagues will continue to study these compounds themselves. This is still very far from being a final drug or vaccine, but it is the most comprehensive study of its kind to date, and researchers hope that it can lay the foundation for new, efficient ways of dealing with malaria.

Ancistrocladus heyneanus.

Rainforest plant may treat pancreatic cancer through ‘antiausterity’ properties

The discovery of a new plant may spell doom for pancreatic cancers everywhere.

Ancistrocladus heyneanus.

Ancistrocladus heyneanus, a close relative of the plant described in this study.
Image credits Vinayaraj / Wikimedia.

Congo’s rainforests may end up curing pancreatic cancer. New research reveals that a vine native to these forests (Ancistrocladus likoko) can dramatically decrease cancerous cells’ survivability, paving the way to new treatments against the disease.

Anti-austerity measures

“The promising antiproliferative and antimetastatic activities of the new alkaloid presented in this paper suggested [it could] be a rewarding candidate for further studies regarding its anticancer potential against human pancreatic cancer,” the paper reads.

Pancreatic cancer is one of the most dangerous, deadly forms this disease can take. Survival rates at the 5-year mark are below 5%. One of the deadliest traits of the disease is that cancerous pancreatic cells spread around extremely aggressively, hogging up all the oxygen and nutrients available around the tumor.

In these conditions, most cells would find it impossible to survive — and, indeed, healthy pancreatic cells quickly start dying. However, pancreatic cancer cells manage to survive, even thrive, under such conditions. This trait, known as ‘austerity’, is perhaps the single most important reason why pancreatic cancer is so deadly and difficult to root out.

Pancreatic cancer cells’ austerity draws on a cell signaling pathway called Akt/mTOR. Finding a compound that can throw a wrench into the Akt/mTOR — so-called ‘antiausterity’ compounds — is a key goal of researchers and doctors in the fight against pancreatic cancer.

Now, an international team of researchers reports finding a new and promising antiausterity alkaloid compound in the Ancistrocladus likoko vine deep in the Congolese rainforest. The team has previously discovered alkaloid compounds with antiausterity potential in other vines in the region, and the present research was spurred by that work.

Cancer antiausterity test.

Ancistrolikokine E3 suppressing the migration of pancreatic cancer cells in a wound-healing assay carried over 48 h. The effect is concentration-dependent, the team explains.
Image credits Suresh Awale et al., 2018, JoNP.

For the study, the team extracted chemical compounds from ground twigs of the vine and separated them using high-performance liquid chromatography. They then analyzed and documented the 3D structure of the new alkaloid — which they christened ancistrolikokine E3.

The alkaloid, the authors report, can successfully inhibit the Akt/mTOR pathway. This effectively allows it to kill pancreatic cancer cells pressed by nutrient starvation, but not when nutrients were plentiful. Ancistrolikokine E3 also inhibited the migration and colonization of cancer cells in mice during lab tests, suggesting that it could also be helpful in staving off metastasis in human patients. The new alkaloid is thus a promising compound for anticancer drug development based on the anti-austerity strategy, the team concludes.

The paper “Ancistrolikokine E3, a 5,8′-Coupled Naphthylisoquinoline Alkaloid, Eliminates the Tolerance of Cancer Cells to Nutrition Starvation by Inhibition of the Akt/mTOR/Autophagy Signaling Pathway” has been published in the Journal of Natural Products.

Rice paddy.

GMO rice may hold the key to fighting HIV on the cheap

How’s that for internal conflict, eh, soccer moms?

Rice paddy.

A rice paddy in the Kerala province, India.
Image credits muffinn / Flickr.

An international team of researchers, with members from Spain, the U.S., and the U.K., plans to fight HIV using only cereal; namely, rice. In a new paper, they describe how they developed a strain of the plant that produces HIV-neutralizing proteins, and how the resulting rice can be used to prevent the spread of this disease.

Rice 2.0

“Our paper provides an approach for the durable deployment of anti-HIV agents in the developing world,” the team writes.

HIV isn’t the death sentence it used to be. Researchers and doctors have had quite a lot of success in developing treatments for people infected with HIV and — at least in more developed countries — death rates associated with HIV have declined significantly. The real prize is to develop a functional vaccine against the virus, an endeavor which has so far borne no fruit.

Still, since we don’t yet have such a vaccine ready, oral medication has been developed that can keep an infection at bay for a limited amount of time. However, such treatments are still expensive — prohibitively so for the many areas in third world countries that are struggling under high rates of HIV infection. Compounding the problem is that production of such drugs — involving a process known as recombinant protein manufacturing — is technologically-intensive and time-consuming, meaning that any production facilities these countries could put together wouldn’t come anywhere near to satisfying demand.

Here’s where the rice comes in. The strain engineered by the team synthesizes the same HIV-neutralizing compounds used in oral medication. Once the crop is fully grown, farmers can process the grains to make a topical cream and apply it to their skin — allowing these active compounds to enter the body. The rice plants produce one type of (monoclonal) antibody and two kinds of proteins that bind directly to the HIV virus (the lectins griffithsin and cyanovirin-N), preventing them from interacting with human cells.

“Simultaneous expression in the same plant allows the crude seed extract to be used directly as a topical microbicide cocktail, avoiding the costs of multiple downstream processes,” the team explains in their paper “This groundbreaking strategy is realistically the only way that microbicidal cocktails can be manufactured at a cost low enough for the developing world, where HIV prophylaxis is most in demand.”

Turning the seeds into cream is a very simple process, the team notes, allowing virtually anybody anywhere to have access to an HIV treatment option if required. It’s also virtually free once you have the rice. The team hopes that people living in areas with high rates of infection will simply grow as much of the rice as they need, potentially providing treatment for whole communities at a time.

However, there’s still work to be done before the GMO rice hits paddies around the world. The team wants to run an exhaustive battery of tests to ensure that their genetic machinations didn’t introduce genes for unknown (and potentially harmful) chemicals in the plants.

They’re also very much aware that GMOs are a subject of much debate, and their efforts might have to suffer from the controversy that has built around GM crops in recent years. There will also be regulatory hurdles to overcome in each part of the world where the rice might be grown and used.

The paper “Unexpected synergistic HIV neutralization by a triple microbicide produced in rice endosperm” has been published in the journal Proceedings of the National Academy of Sciences.

Pot twist: Cannabis component helps fight addiction in new study

A new study published in the journal Neuropsychopharmacology has revealed that a non-psychoactive and non-addictive ingredient of the Cannabis sativa plant can help reduce the risk of relapse among cocaine and alcohol addicts. According to lead author Friedbert Weiss, non-psychoactive cannabinoids could have important medical benefits in the fight against substance addiction.

Image via Pixabay/futurefilmworks

Addiction is a powerful, vicious monster that lives inside yourself. The battle is an extremely hard one and it often carries stretches out over years and years — potentially for an entire life. Many abstinent addicts find it even harder to control themselves in drug-related settings or when they experience stress or higher levels of anxiousness. For them, it’s a true struggle to dismiss their impulses when offered an addictive drug like alcohol or cocaine.

Researchers wanted to study the effect of Cannabidiol (CBD) on drug relapse in a rat model. CBD is a non-psychoactive compound of the plant Cannabis sativa (I suppose you already know that’s weed). CBD has been considered as a treatment for neurological and psychiatric disorders, and more recently also as a treatment for drug and alcohol addiction.

“The efficacy of the cannabinoid [CBD] to reduce reinstatement in rats with both alcohol and cocaine – and, as previously reported, heroin – histories predicts therapeutic potential for addiction treatment across several classes of abused drugs,” says Weiss.

Scientists applied a gel containing CBD once per day for a week to the skin of lab rats. The rodents had a history of deliberate daily alcohol or cocaine self-administration, leading to addiction-like behavior.

Next, they performed a number of tests to observe the rats’ reaction to stressful and anxiety-provoking situations, as well as behavior tests that measured impulsivity — a psychological trait associated with drug addiction. The research team reported that CBD reduced relapse provoked by stress and drug cues. CBD also reduced anxiety and impulsivity in the rats.

The authors wrote: “CBD attenuated context-induced and stress-induced drug seeking without tolerance, sedative effects, or interference with normal motivated behavior. Following treatment termination, reinstatement remained attenuated up to ≈5 months although plasma and brain CBD levels remained detectable only for 3 days. CBD also reduced experimental anxiety and prevented the development of high impulsivity in rats with an alcohol dependence history.”

Authors hope that insight into the mechanisms by which CBD exerts these effects will be investigated in future research. They believe that the findings are proof of CBD’s potential in relapse prevention, CBD’s major benefits being its actions across several vulnerability states, and long-lasting effects with only brief treatment.

“Drug addicts enter relapse vulnerability states for multiple reasons. Therefore, effects such as these observed with CBD that concurrently ameliorate several of these are likely to be more effective in preventing relapse than treatments targeting only a single state,” Weiss concludes.

Miami launches bacteria-infected mosquitoes to fight Zika virus

The Miami-Dade County website released a statement which announces that the Wolbachia infected mosquitoes will be released in South Miami to combat Zika virus.

Credits: Pixabay/ekamelev

These mosquitoes are lab-grown by the Kentucky-based company MosquitoMate. The test is in collaboration with the Miami-Dade County Mosquito Control and Habitat Management Division.

Wolbachia is a naturally-occurring bacterium present in up to 60 percent of all the different species of insects around us, mosquitoes included. Researchers discovered that when infected male mosquitoes mated with non-infected females, the eggs did not hatch, hence reducing mosquito populations.

These Male mosquitoes do not bite (they feed on pollen) and are friendly to the environment by increasing pollination.

A one-half-square-mile treatment area and a similarly-sized control area will be designated within the City of South Miami. Surveys of the Aedes aegypti populations will be taken before and after weekly or twice-weekly treatments.

Successful trials in Kentucky, California, and New York have been carried out by MosquitoMate. Scientists registered significant reduction of Aedes aegypti female populations. The reduction only affected this species of mosquitoes.

Last spring, a similar trial took place in Key West but ended prematurely due to Hurricane Irma’s landfall. The results are still pending.

 

A type 2 diabetes drug might treat Alzheimer’s

A three-agent drug used to treat type 2 diabetes mellitus shows significant results for boosting memory and learning skills in aging mice suffering from Alzheimer’s disease.

Neurological degenerative diseases, such as Alzheimer’s, Parkinson’s, or Huntington’s, share common features with type 2 diabetes mellitus. Aging, high-cholesterol levels, neuronal degeneration, blood vessel abnormalities, increased oxidative stress and increased inflammatory response are some of the shared features.

Source: Pixabay/GDV

Insulin is a pancreatic hormone that allows glucose to pass from the bloodstream through the cell’s membrane. In type 2 diabetes, insulin is still produced, but at lower levels, and some peripheric tissues become resistant to it. This pathology affects all cells, but the neuron is one of the biggest victims of glucose deprivation. The incidence of Alzheimer’s, Parkinson’s, and other neurological disorders is higher in type 2 diabetes patients, suggesting that they have similar causes of development. This information gave scientists the idea of using diabetic drugs to treat neurological diseases.

The triple agent drug tested on transgenic mice by professor Christian Holscher from Lancaster University contains GLP-1, GIP, and glucagon. GLP-1 and GIP are two incretins, gastrointestinal hormones that increase insulin production and act as brain growth factors.

Via Pixabay/silviarita

The researchers induced mutations in the APP/PS1 genes of the mice, to make them resemble human patients suffering from a form of hereditary Alzheimer’s. Next, scientists tested aging mice who received the antidiabetic treatment in a maze and compared their performances to a group of controls. The results showed that treated mice had enhanced cerebral activity, solving the maze faster than the others. The researchers found higher levels of brain growth factors, reduced amyloid plaques (found in Alzheimer’s), reduced chronic inflammation, reduced oxidative stress, and slowed the rate of brain cell loss.

“These very promising outcomes demonstrate the efficacy of these novel multiple receptor drugs that originally were developed to treat type 2 diabetes but have shown consistent neuro-protective effects in several studies”, said professor Christian Holscher to the Lancaster Guardian journal.

Via Pixabay/qimono

Dr. Doug Brown, Director of Research and Development at Alzheimer’s Society, which co-funded this study, openly supports the research.

“Although the benefits of these ‘triple agonist’ drugs have so far only been found in mice, other studies with existing diabetes drugs such as liraglutide have shown real promise for people with Alzheimer’s, so further development of this work is crucial”, he stated in a press release.

The paper was published in the journal Brain Research on the first day of this year.

The Possibilities of Tailored Medical Treatments from IP Stem Cells and the Man Who Made it Possible

Imagine that we could scrape a few cells from our skin and send them to the lab. Within a few days, the lab would deliver a therapy or medicine specifically tailored to treat a devastating disease that we had unfortunately developed. These selfie-cells, programmed to treat our specific diseases, could be transplanted or injected on-site without the worry of immune rejection.

Shinya Yamanaka, photo by Rubenstein via Flickr.

Thanks to Dr. Shinya Yamanaka, a Nobel Prize-winning Japanese stem cell researcher, this customized treatment is in our near future. In 2006, he found that by using only a few genetic, nuclear factors, it was possible to take skin cells from mice and turn back the developmental clock. These cells reverted in potency to a status termed Induced Pluripotent Stem Cells (IPSCs). The creation of IPSCs has led researchers in regenerative medicine and drug discovery on an accelerated pathway with new methods to approach diseases.

While these IPSCs are similar to Embryonic Stem Cells (ESCs), they derive from the patient’s own skin. In essence, patients are the source of their own treatments.

The use of ESCs stirs ethical controversy because these cells source from an embryo. ESCs are totipotent, meaning that these cells have the ability to become any desired cell type. ESCs have the potential to develop an entire organism.

Lack of Federal Funding for ESC Research Led to Discovery of IPSCs

While ESCs are useful, they present more challenges for scientists to obtain and use them. From 2001 until 2009, it was not possible to obtain federal funding for any research that included ESCs. Researchers in many fields of science were forced to look for alternatives. Despite this eight-year funding ban, a silver lining emerged – it led to the discovery of IPSCs.

IPSCs are the next level of stem cell. Pluripotency implies the capacity for stem cells to become a number of different cell types, but that does not necessarily provide the ability to develop an entire organism. Induced with a set of factors, as Dr. Yamanaka showed, skin cells can turn back their state of potency or be reprogrammed.

It’s like turning back the developmental time clock in a fully differentiated cell. A cell that was once a skin fibroblast could now become a neuron if it was induced in a microenvironment. For example, it would now be possible to take skin cells from an Alzheimer’s disease patient and develop an in-vitro human cell culture model, since these cells can grow indefinitely. When the reprogramming occurs to create IPSCs, they become immortal, which is a key feature in their utility.

In the 10 years since Dr. Yamanaka discovered IPSCs, regenerative medicine and drug discovery-development have accelerated forward in the use of these cells. Diseases such as Alzheimer’s, Parkinson’s, Huntington’s and Down’s syndrome now have models that forego the use of ethically controversial ECSs. For drug screening and development, IPSCs are in use for in-vitro studies since these cells are capable of immortal growth in culture and provide genuine, human testable models. New drugs can be screened against cell culture models to determine their safety and efficacy, thanks to IPSCs.

IPSC Research Suggests Potential to Treat and Cure Incurable Diseases

Dr. Yamanaka was recognized for his contribution and awarded a Nobel Peace Prize in 2012 for his work that led to the discovery of IPSCs. Currently, Dr. Yamanaka and his team continue to probe the in-depth mechanisms of how somatic cells are reprogrammed to the pluripotency state.

As research efforts continue forward with IPSCs, we will see more models developed to study diseases, approaches to treat them and the development of new drugs. Perhaps in our not-so-distant future, the most remarkable step forward with IPSCs will be our own cells used to treat and cure diseases we once considered incurable.

About the Author

Dr. Christy A. Rothermund-Franklin is an associate professor for the school of STEM at American Public University. She earned her B.S. in biotechnology from the University of Nebraska and a Ph.D. in biochemistry and molecular biology from the University of Nebraska Medical Cente

Researchers zoom in on potential treatment for prostate cancer

Researchers at the University of Georgia may be zooming in on a treatment for prostate cancer. Their new therapy shows great efficacy for mouse models, and the treatment is expected to go in human trials.

Somanath Shenoy is an associate professor of Clinical and Experimental Therapeutics in the University of Georgia College of Pharmacy. Image via University of Georgia.

Prostate cancer is the second most common type of cancer, killing some 10,000 people in the UK every year (rates vary greatly across the world), with most men over 50 being at a very high risk of disease. The proposed treatment inhibits the activity of a protein called PAK-1. PAK-1 is responsible for the development of highly invasive prostate cancer cells.

“PAK-1 is kind of like an on/off switch,” said study co-author Somanath Shenoy, an associate professor in UGA’s College of Pharmacy. “When it turns on, it makes cancerous cells turn into metastatic cells that spread throughout the body.”

The solution they propose bears a similar name – IPA-3. IPA-3 is a molecule which limits the activity of PAK-1 proteins. Shenoy and Brian Cummings, an associate professor in UGA’s College of Pharmacy, packed IPA-3 in a bubble-like structure called a liposome and injected it intravenously. The liposome shell surrounding IPA-3 ensures that it is not metabolized by the body too quickly, allowing the inhibitor enough time to disrupt the PAK-1 protein. Hitting this timing is important for the disruption of PAK-1.

They found that following this treatment,

“When we first began these experiments, we injected IPA-3 directly into the bloodstream, but it was absorbed so quickly that we had to administer the treatment seven days a week for it to be effective,” Shenoy said. “But the liposome that Dr. Cummings created makes the IPA-3 much more stable, and it reduced the treatment regimen to only twice a week.”

The preliminary results are really good, but there is still a while before we can test this on humans. They’ve shown that the treatment can work, now they have to see what negative side effects it could have.

“The results of our experiments are promising, and we hope to move toward clinical trials soon,” he said, “but we must figure out what side effects this treatment may have before we can think about using it in humans.”

Drug candidate destroys Malaria in 48 hours

Malaria is one of the most common and dangerous diseases in the world, with the World Health Organization estimating over 200 million cases every year. There are several ways to try to treat malaria, but the results are debatable and often times not as effective as desired. Now, a team has demonstrated a new compound which effectively destroys malaria in 48 hours.

malaria

Malaria is a disease caused by parasitic protozoans (a type of single cell microorganism) which are carried by mosquitoes – if the mosquito bites you and sucks your blood, it also injects the parasite. The most affected countries are in Africa, but there is also a high incidence in South-East Astia and South America; it is associated with poverty, especially in areas with warm and wet climates which encourage the development of mosquito populations. It’s estimated that in Africa alone, the disease causes damages of $12 billion every year due to increased healthcare costs, lost ability to work and effects on tourism. Despite a need, no effective vaccine exists, although several promissing efforts to develop one are ongoing. The best way to fight the disease is to prevent mosquito bites with net and insect repellants, but when that doesn’t work and people do get infected, treatment options are often times limited and not very effective.

Now, researchers from St. Jude Children’s Research Hospital believe they have found a very good treatment for malaria. They developed a compound which targets only the red blood cells infected by the disease, leaving the healthy ones alone and basically wiping out the disease in 48 hours. Planning has begun for safety trials of the compound in healthy adults.

The compound is called (+)-SJ733, and it was identified in a previous study, with scientists now showing its effectiveness against malaria. In a mouse model of malaria, a single dose of (+)-SJ733 killed 80 percent of malaria parasites within 24 hours, and after another 24 hours, the parasite was undetectable. To make things even more interesting, the way the compound acts suppress development of drug-resistant parasites, which is very important.

A new report says that the rapid action of (+)-SJ733 will likely slow malaria drug resistance. Credit: Peter Barta, St. Jude Children’s Research Hospital

“Our goal is to develop an affordable, fast-acting combination therapy that cures malaria with a single dose,” said corresponding author R. Kiplin Guy, Ph.D., chair of the St. Jude Department of Chemical Biology and Therapeutics. “These results indicate that SJ733 and other compounds that act in a similar fashion are highly attractive additions to the global malaria eradication campaign, which would mean so much for the world’s children, who are central to the mission of St. Jude.”

My first reaction when I read the article was to be a bit worried. I mean, destroying infected red blood cells… that sounds a bit dangerous, right? Well, it’s actually really safe, and here’s why.

The way the malaria infection develops is as following – after an infection, you don’t get sick immediately. The disease first travels to the liver, where it stays for 1-4 weeks (usually); this is the incubation period. After the incubation period, the disease destroys the infected liver cells and enters the bloodstream. There, they infect the Red Blood Cells (RBC). They enter a RBC and multiply more and more until they burst out of it and move on to the next. This is generally why malaria causes cyclic fever – whenever it bursts out of RBCs and goes into the blood stream, you get a fever. RBCs are produced in bone marrow and normally have a life span of 3-4 months, after which they age and are destroyed by the body. The thing is, an infected RBC would be destroyed anyway by the virus – the drug does it in a nicer and safer way for the body – the compound isn’t destroying any additional cells.

“With this drug, only the red blood cells with a malaria parasite in them are affected. The malaria parasites life cycle is ~48 hours when it is infecting red blood cells, so you don’t actually “kill.. someone’s red blood cells” any more than if they weren’t taking the drug”, one of the authors said in a Reddit comment.

Planning has already begun for clinical trials; if the drug is deemed safe, it will start soon. It won’t hit the shelves anytime soon, as clinical trials tend to last for several years.

Journal Reference:

  1. María Belén Jiménez-Díaz, Daniel Ebert, Yandira Salinas, Anupam Pradhan, Adele M. Lehane, Marie-Eve Myrand-Lapierre, Kathleen G. O’Loughlin, David M. Shackleford, Mariana Justino de Almeida, Angela K. Carrillo, Julie A. Clark, Adelaide S. M. Dennis, Jonathon Diep, Xiaoyan Deng, Sandra Duffy, Aaron N. Endsley, Greg Fedewa, W. Armand Guiguemde, María G. Gómez, Gloria Holbrook, Jeremy Horst, Charles C. Kim, Jian Liu, Marcus C. S. Lee, Amy Matheny, María Santos Martínez, Gregory Miller, Ane Rodríguez-Alejandre, Laura Sanz, Martina Sigal, Natalie J. Spillman, Philip D. Stein, Zheng Wang, Fangyi Zhu, David Waterson, Spencer Knapp, Anang Shelat, Vicky M. Avery, David A. Fidock, Francisco-Javier Gamo, Susan A. Charman, Jon C. Mirsalis, Hongshen Ma, Santiago Ferrer, Kiaran Kirk, Iñigo Angulo-Barturen, Dennis E. Kyle, Joseph L. DeRisi, David M. Floyd, R. Kiplin Guy. ( )-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance ofPlasmodium. Proceedings of the National Academy of Sciences, 2014; 201414221 DOI: 10.1073/pnas.1414221111

Everything you wanted to know about homeopathy but never asked

Last week we described a study which concluded that homeopathy is nothing more than a placebo effect — it was just one of the many scientific studies which found the same thing. But many people swear by homeopathy and, judging from what’s happening in the comment section and our inbox, they feel very strongly about it. So let’s take a step back, analyze what’s happening with homeopathy, and then we can all our own conclusions.

The mechanism behind homeopathy

Samuel Hahnemann, the originator of homeopathy, 1796. He believed that “Like cures like”, dilution increases potency, and diseases are caused by miasms.alleged predispositions to a particular disease.

Homeopathy is a system of alternative medicine proposed in 1796 by Samuel Hahnemann, based on his doctrine of “like cures like”. Essentially, the belief is that the same thing which makes you sick can be used to heal you. Hahnemann believed that all diseases are caused by miasms, and homeopathy can be used to eliminate them. Not familiar with the term? Probably because it’s long been disproven.

Truth be told, not all homeopaths today believe in the so-called miasm theory — but all homeopathy is based on like-cures-like — using “active substances” to address all sorts of problems.

These active substances are things which cause symptoms similar to that of a disease, in the belief that if the body recognizes the symptom, it will start to fight the real disease. But it has to be diluted — a lot.

Hahnemann has this idea that undiluted doses intensify the symptoms and exacerbate the condition, sometimes causing dangerous toxic reactions. He specified that the substances be diluted due to his belief that succussion activated the “vital energy” of the diluted substance and made it stronger.

So the proposed cures are prepared by dilution. You take the active substance (whatever that may be) and usually dilute it by putting one drop of it in 1 liter of alcohol or distilled water, and then you mix it. After the mixing, you take 1 drop of this newly obtained substance and put it in another fresh liter of alcohol or distilled water, rinsing and repeating the process many times, until well past the point where none of the original molecules remain. The more diluted the substance is, the more effective the “cure” will be. The idea is that the alcohol or distilled water will somehow “remember” the molecule and have an impact on your body. Right of the bat, this goes directly against basic science — not something a pharma company or another is saying but against well-established, basic medical (and chemical) science.

But wait, you’ll say, how can you be sure that there is no more molecule in the substance? Well, we’ll have to get a little familiar with Avogadro’s number. Avogardo was a brilliant chemist (not related to homeopathy in any way). He showed that for every mole (unit of substance) of a substance, there are 6.02214129(27)×1023 constituents (atoms or molecules). For example, in a mole of OH, there are 6.02214129(27)×1023 molecules of OH – and the same goes for every substance. Let’s not get into how he arrived at that conclusion as that’s a different discussion, but his number is one of the very foundations of modern chemistry.

homeopathy2

Via Popular Science.

So if you have a substance and you dilute it up to the point where its concentration starts to outweigh Avogadro’s number, you end up with no more molecules of the initial substance. Say, if you take a gram of a substance and you put it in a kilogram (1000 grams), the concentration will be 10-3. If you take a gram of the new substance and put it in another fresh kilogram, it will be 10-6 and so on. If you do this 8 times, you reach a concentration of 10-24, which outweighs Avogadro’s number — and that’s when you don’t have any more molecules of the initial substances. Homeopathy often goes way past that number, and there’s just nothing left in to have an effect — even if you assume that the method works.

But does the method really work?

What science says about homeopathy

There is little room for discussion or interpretation here — although there’s been no lack of trying. Study after study has tried to find evidence or even just a workable mechanism for homeopathy, but they’ve found the exact opposite. There’s no mechanism behind homeopathy, and there’s no effect past a placebo.

If this was the case, and water did have a “memory,” we would have to rewrite all of science as we know it. Even ignoring the centuries of scientific research disproving homeopathy, a simple thought experiment can show go a long way when it comes to the process.

Just imagine: in its history, water will have contacted literally millions of other substances, and by this thought process, it has a memory of all of them — so just drinking a glass of regular water should make you immune to a swarm of diseases, right? So then why even have homeopathy — water is naturally diluting all sorts of things, so we should kind of be immune to everything, right?

Lastly, even if there were any active substance, and even if water would have a memory, something that causes symptoms similar to the X disease doesn’t cure X disease. That’s just wishful thinking, and there is nothing to suggest that this works. The scientific consensus is pretty strong on this case. Here are just a few studies:

The list goes on and on.

So why does it seem to work?

OK, but by quoting some of the common responses, lots of people still stand by homeopathy. You often hear things like “This worked for me”, “It worked for millions of people”, and “How can you say it doesn’t work?” Well, here are some of the reasons why homeopathy may appear to work:

a) unassisted natural healing – Your body is awesome at self-healing. Some people are more resilient than others, but generally speaking, your body heals itself all the time. It can eliminate even strong diseases on its own.

b) the placebo effect – Simulated treatments are surprisingly effective in many cases. Combine this with your self-healing, and you get quite a powerful tool.

c) the consultation effect – Modern research has shown that if you just go to the doctor and receive a consultation, the care, concern, and reassurance a patient experiences when opening up to a compassionate caregiver (read: homeopath) can have a positive effect.

d) unrecognized treatments – An unrelated food, exercise, environmental agent, or treatment for a different ailment may have occurred. Maybe you drank a lot of green tea, or that trip to the ocean did wonders for your lungs.

e) regression towards the mean – Many diseases and conditions are cyclical — the symptoms get naturally stronger and weaker in time. Since patients tend to seek care when discomfort is greatest, it’s pretty likely that the symptoms will naturally get weaker.

f) cessation of unpleasant treatment – Many times, homeopaths recommend the ceasing of conventional treatments — this is extremely dangerous and should never be done without consulting an actual medical doctor. Oftentimes, the conventional treatment causes some unpleasant side effects, perhaps even more so than the disease’s symptoms. When you stop taking the treatment, the side effects may go away, but the disease remains and gets.

But even so, what harm can homeopathy actually do?

You may try to go for a win-win strategy, and take both conventional treatments and homeopathic treatments — what have you got to lose, right? Well, technically, nothing. Homeopathy doesn’t do anything bad because, well, it doesn’t really do anything!

The main problem is using only homeopathy as a treatment. This can be very dangerous, as has been shown numerous times; when homeopathy is used in place of real medicine, the risks are real. From Calgary, an avoidable child death has been linked to the use of homeopathy instead of medicine. In 2002, 1-year-old Isabella Denley was prescribed medications for her epilepsy. Instead of using them, her parents consulted an iridologist, an applied kinesiologist, a psychic and an osteopath. She was being treated purely with homeopathic medication when she died. The infant girl, Gloria Thomas, died of complications due to eczema which was treated only with homeopathy. Eczema! This is an easily manageable disease, and her parents were declared guilty of manslaughter — and rightfully so.  By the time she died, she was the weight of an average three-month-old, her body was covered with angry blotches and her once black hair had turned completely white.

These are not isolated cases. Using homeopathy instead of real treatment is dangerous, and you should not do it! If you are rejecting medicine and treating your child only with homeopathy, you’re putting him or her at risk. That’s the bottom line, and there’s no going around it. As Bad Astronomy’s Phil Plait puts it, it is “perhaps the most ridiculous of all ‘alternative’ medicines, since it clearly cannot workdoes not work, and has been tested repeatedly and shown to be useless.” Even though this relatively simple and highly manageable disease killed his daughter, Thomas Sam stood by his beliefs in homeopathy — don’t make the same mistake!

Spoiler alert: no, they are not.

I’d like to make a special mention of homeopathic vaccination — not receiving your (or your child’s) vaccines is especially dangerous, and, as with other treatments, homeopathic vaccinations don’t do anything.

A note on natural remedies

There is a lot of confusion with people mistaking homeopathy with naturopathic treatments. That’s a separate discussion, but for now, let’s just say that the two things are very different. Natural remedies (herbs, teas, plants, etc) are not homeopathy. You should always consult with your doctor or pharmacist before taking anything, and only follow treatments prescribed by an authorized physician.