Tag Archives: parkinson

A drug used for decades for liver diseases could effectively slow down Parkinson’s

It seems like re-purposing drugs can be a gold mine for future drug development. Now, scientists have discovered that a drug used for decades in liver treatments might effectively slow down Parkinson’s disease.

Parkinson’s disease is a degenerative disorder of the central nervous system mainly affecting the motor system. It’s a nasty condition, and there is no effective treatment for it – we don’t even fully understand why it occurs in some people. But now, medics might be getting an unexpected ally: ursodeoxycholic acid (UDCA).

I say unexpected because UDCA has already been in clinical use for decades, but for a completely different problem. Also, since it’s been used in treatments, we already know that it’s safe, so this new treatment could hit the markets much sooner. Dr Heather Mortiboys, Parkinson’s UK Senior Research Fellow from the University of Sheffield, explained:

“We demonstrated the beneficial effects of UDCA in the tissue of LRRK2 carriers with Parkinson’s disease as well as currently asymptomatic LRRK2 carriers. In both cases, UDCA improved mitochondrial function as demonstrated by the increase in oxygen consumption and cellular energy levels.”

The rest of the team echoed his optimism. Oliver Bandmann, Professor of Movement Disorders Neurology at the University of Sheffield added:

“Whilst we have been looking at Parkinson’s patients who carry the LRRK2 mutation, mitochondrial defects are also present in other inherited and sporadic forms of Parkinson’s, where we do not know the causes yet. Our hope is therefore, that UDCA might be beneficial for other types of Parkinson’s disease and might also show benefits in other neurodegenerative diseases.”

There is a tremendous need for Parkinson treatments, especially as it affects approximately seven million people globally and one million people in the United States. We need something to happen in years, not decades. Dr Arthur Roach, Director of Research and Development at Parkinson’s UK, which part-funded the study, said:

“There is a tremendous need for new treatments that can slow or stop Parkinson’s. Because of this urgency, the testing of drugs like UCDA, which are already approved for other uses, is extremely valuable. It can save years, and hundreds of millions of pounds. It’s particularly encouraging in this study that even at relatively low concentrations the liver drug still had an effect on Parkinson’s cells grown in the lab.”

Journal Reference:

  1. H. Mortiboys, R. Furmston, G. Bronstad, J. Aasly, C. Elliott, O. Bandmann. UDCA exerts beneficial effect on mitochondrial dysfunction in LRRK2G2019S carriers and in vivo. Neurology, 2015; DOI: 10.1212/WNL.0000000000001905

 

Scientists successfully implant new neurons into the brain

Scientists from the University of Luxembourg have for the first time successfully grafted neurons reprogrammed from skin cells into the brains of mice, obtaining long term stability; six months after the procedure, the neurons were fully integrated into the brain. This procedure raises new hopes for replacing sick neurons with new ones, especially for patients suffering from degenerative diseases such as Parkinson’s.

The group was led by Prof. Dr. Jens Schwamborn and Kathrin Hemmer and is focused around finding solutions for people suffering from currently untreatable degenerative diseases. Their answer was to simply replace the old, sick neurons, with new ones, and see if it works. So far, their technique has proven successful in mice, but even with such promising results, there’s still a long way before human treatment can be discussed.

“Successes in human therapy are still a long way off, but I am sure successful cell replacement therapies will exist in future. Our research results have taken us a step further in this direction,” declares stem cell researcher Prof. Schwamborn, who heads a group of 15 scientists at LCSB.

In order to do this, they reprogrammed skin cells to act as neurons, creating stable nerve tissue in the brain. Their technique of using cells from the same mouse (skin cells) drastically improves the compatibility of the implanted cells. Even in the initial results, 6 months after the implantation, mice showed to signs of rejection or incompatibility. Furthermore, the neurons exhibited normal activity and were connected to the original brain cells via newly formed synapses, the contact points between nerve cells.

Again, these are just the initial results, but scientists are confident in further developing the technique and implementing it in humans – something which they believe will happen relatively soon. In the future, implanted neurons could produce dopamine and/or transport it in the brain. This is the next step in their research.

“Building upon the current insights, we will now be looking specifically at the type of neurons that die off in the brain of Parkinson’s patients – namely the dopamine-producing neurons,” Schwamborn reports.

Read the full paper here.

Scientific Reference: Hemmer K., Zhang M., van Wüllen, T., Sakalem M., Tapia N., Baumuratov A., Kaltschmidt C., KaltschmidtB, Schöler H. R., Zhang W., Schwamborn J. C. (2014) Induced neural stem cells achieve long-term survival and functional integration in the adult mouse brain. Stem Cell Reports, accepted, DOI: http://dx.doi.org/10.1016/j.stemcr.2014.06.017

 

 

Skin cells of a monkey reverse engineered into stem cells

Researchers have managed to take skin cells from monkeys, reverse engineer them into stem cells, and then transplant into the monkeys’ brain where they successfully became brain cells. This technique holds massive promise for treating mental degenerative diseases.

schame

The generation of induced pluripotent stem cells (iPSCs) opens up the possibility for personalized cell therapy. Using Rhesus monkeys iPSC-derived neural progenitors, they developed neurons, astrocytes, and myelinating oligodendrocytes (all types of brain cells).

This was done in primates, which are obviously closer to us than rats – and closer to humans is always better. Also, this method created no tumor formation in vivo, nor any other type of negative immune response.

The main problem with this study is that they did not see any functional improvement after transplantation based on behavioral recovery or PET data. Also, while the study is a proof of concept, it still isn’t very comprehensive. They showed that differentiated cells can engraft successfully into their injured brain region. No functional recovery occurred (yet), but what’s really really good is that no tumors were caused as well.

parkinsons-phase-cancellation

Parkinson’s tremors significantly reduced after electrical signal cancels brain waves

Credit: John-Stuart Brittain et al./Current Biology

Credit: John-Stuart Brittain et al./Current Biology

For most Parkinson’s patients, tremors associated with this devastating disease make living a normal life extremely difficult, if not impossible. Cooking, eating, even tying one’s shoelaces, basically anything that implies limb manipulation is very difficult to achieve by one’s self. A novel type of therapy developed by physicians at Oxford University, however, brings a glimmer of hope that Parkinson’s patients might have the chance at living a normal life once again; their findings showed a 50% decrease in tremors after applying an electrical current to key motor areas of the brain.

There are a number of drugs and treatments that address Parkinson’s tremors. However most patients don’t respond properly or only show mild improvements – far from enough. The best improvements in alleviating tremors have been found using  deep brain stimulation, a technique that involves surgery to insert electrodes deep into the brain itself to deliver electrical impulses.

As you can imagine, this particular method isn’t really appealing to patients seeing how their skulls need to be open and have electrodes fitted inside the brain – not to mention the health hazards that might surface, like brain bleeding and the likes.

Oxford University researchers have reached much of the same or better results as brain stimulation using a method that does not imply surgery, by applying electrical signals with electrodes fitted on the scalp, instead of embedded inside the brain itself.

Cancelling Parkinson’s tremor causing brain waves

Credit: John-Stuart Brittain et al./Current Biology

Credit: John-Stuart Brittain et al./Current Biology

Called transcranial alternating current stimulation (TACS), the technique involves placing electrode pads on the outside of the patient’s skull, one close to the base of the neck and one on the head, above the motor cortex (part of the brain implicated in controlling the tremors).

The science behind it is simply mind-boggling. Basically, our brain operates in brain waves, so by stimulating the brain with matching waves, one can amplify that particular wave or, in the case of Parkinson’s caused tremor brain waves, cancel them out.

Thus, a small alternating current stimulation is passed through the electrodes that delivers an oscillating tremor signal at 180 out of phase to cancel it out, suppressing the physical tremor. As an analogy, some of you might be familiar with noise-canceling headphones: when you turn them on, the headphones detect ambient noise and deliver a signal that cancels it out so you basically don’t hear anything besides a faint beep. Achieving a similar effect, however, with particular brain waves is simply amazing!

The technique was tested on 15 people with Parkinson’s disease at Oxford‘s John Radcliffe Hospital, and resulted in a 50%  reduction in resting tremors among the patients.

“Tremors experienced by Parkinson’s sufferers can be devastating and any therapy that can suppress or reduce those tremors significantly improves quality of life for patients. We are very hopeful this research may, in time, lead to a therapy that is both successful and carries reduced medical risks. We have proved the principle, now we have to optimize it and adapt it so it is able to be used in patients.”

Now, the next step the researchers plan on making is to devise electrodes small, yet still potent enough to work, that can be implanted beneath the skin of patient’s skull, as well as a portable system that detects the brain signal and adjusts the delivered stimulation to cancel it out.

Findings were reported in the journal Current Biology.

 

 

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Intelligent nanoparticles drop anti-aging cargo

A group of researchers have successfully tested a novel nanodevice treatment, in which intelligent nanoparticles selectively open and release drugs which target aging cells. The approach could render results when treating patients suffering from diseases involving tissue or cellular degeneration such as cancer, Alzheimer’s, Parkinson’s, accelerated aging disorders (progeria). It could also boosts results in the cosmetic industry, where anti-aging products are always welcomed.

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Intracellular controlled release of molecules within senescent cells was achieved using mesoporous silica nanoparticles (MSNs) capped with a galacto-oligosaccharide (GOS) to contain the cargo molecules (magenta spheres; see scheme). The GOS is a substrate of the senescent biomarker, senescence-associated β-galactosidase (SA-β-gal), and releases the cargo upon entry into SA-β-gal expressing cells.

Senescence is a physiological process of the body to eliminate aged cells or ones with alterations that may compromise their viability. In young, healthy bodies the senescence mechanisms prevents the accumulation of aged cells (senescent) in organs and tissues, which disrupts their proper functions, and sometimes lead to the apparition of tumors. As we continue to age, though, senescent accumulation is inevitable and age related diseases surface. The elimination of these cells would slow down the appearance of diseases associated with aging.

“The nanodevice that we have developed consists of mesoporous nanoparticles with a galactooligosaccharide outer surface that prevents the release of the load and that only selectively opens in degenerative phase cells or senescent cells. The proof of concept demonstrates for the first time that selected chemicals can be released in these cells and not in others,” says Ramón Martínez Máñez, researcher at the IDN Centre — Universitat Politècnica de València and CIBER-BBN member.

The scientists tested the new nanodevice in cell cultures derived of patients with accelerated aging syndrome dyskeratosis congenita. These cell cultures are characterized by a high concentration of senescent cells, due to high levels of beta-galactosidase activity – an enzyme which is associated with senescence. The researchers designed nanoparticles that open when the enzyme is detected release their contents in order to eliminate senescent cells, prevent deterioration or even reactivate for their rejuvenation.

“There are a number of diseases associated with premature aging of tissues, many of which affect very young patients and for whom there is no therapeutic alternative, as in the case of DC or aplastic anemia. Other diseases affect adults, as idiopathic pulmonary fibrosis or liver cirrhosis. These nanoparticles represent a unique opportunity to selectively deliver therapeutic compounds to affected tissues and rescue their viability and functionality” explains Rosario Perona, researcher at the Instituto de Investigaciones Biomédicas (CSIC/UAM) and CIBERER member.

The next step of this research is to test the devise with therapeutic agents and validate it in animal models.

“As far as we know this is the first time that a nanotherapy for senescent cells has been described. Although there is still far to go from these results to the possible elimination of senescent cells or rejuvenation therapies, we believe that our research may open new paths for developing therapies for the treatment of age-related diseases,” says Ramón Martínez Máñez.

Findings were published in the journal Angewandte Chemie International.

Protein re-assembly

New method allows visualizing of protein self-assembly – paves way for nanotech against diseases

Be it a bacteria or a fully complex being, say a human, all living, biological organisms undergo lighting fast protein structure reassembly in response to environmnetal stimuli. For instance,  receptor proteins in the sinus are stimulated by various odor molecules, basically telling the organism that there’s food nearby or it’s in the vicinity of danger (sulphur, methane, noxious fumes). By studying these mechanisms, scientists can better understand these process. A great leap further in the field was achieved by researchers at  the University of Montreal, who’ve managed to image how proteins self-assemble.

Protein re-assembly

Here shown are two different assembly stages (purple and red) of the protein ubiquitin and the fluorescent probe used to visualize these stage (tryptophan: see yellow). Credit: Peter Allen.

Understanding and mapping these process helps pave a broader, more plastic picture of how organisms function from a molecular assembly mechanism point of view, but maybe most importantly aids in pinpointing assembly errors. Both Alzheimer’s and Parkinson’s, two of the most devastating neural degenerative disease currently plaguing mankind, are caused by errors in molecular assembly. According to Professor Stephen Michnick, the research is expected to help bioengineers design new molecular machines for nanotechnology applications which might fight these diseases.

“In order to survive, all creatures, from bacteria to humans, monitor and transform their environments using small protein nanomachines made of thousands of atoms,” explained Michnick.

Proteins are composed of linear structural chains of amino acids, which have the capability to self assemble at the rate of thousandth of a second into a nanomachine by virtue of millions of years of evolution. Determining how these proteins self-assemble is a crucial goal in biotechnology at the moment, however, this extremely fast assembly velocity, as well as the numerous possible combinations, makes it extremely difficult.

“One of the main challenges for biochemists is to understand how these linear chains assemble into their correct structure given an astronomically large number of other possible forms,” Michnick said.

Researcher Dr. Alexis Vallée-Bélisle expressed similar sentiments.

“To understand how a protein goes from a linear chain to a unique assembled structure, we need to capture snapshots of its shape at each stage of assembly,” Vallée-Bélisle noted.

The researchers sought to overcome these setbacks, and successfully established a new method for visualizing the process of protein assembly by attaching fluorescent probes at all points on the linear protein chain.

“The problem is that each step exists for a fleetingly short time and no available technique enables us to obtain precise structural information on these states within such a small time frame. We developed a strategy to monitor protein assembly by integrating fluorescent probes throughout the linear protein chain so that we could detect the structure of each stage of protein assembly, step by step to its final structure.”

However, Vallée-Bélisle emphasized that the protein assembly process “is not the end of its journey,” as a protein can change, via chemical modifications or with age, to take on different forms and functions.

“Understanding how a protein goes from being one thing to becoming another is the first step towards understanding and designing protein nanomachines for biotechnologies such as medical and environmental diagnostic sensors, drug synthesis of delivery,” he added.

The research is funded by Le fond de recherché du Québec, Nature et Technologie and the Natural Sciences and Engineering Research Council of Canada. The findings were published in the journal Nature Structural & Molecular Biology.’

source: U Montreal.

Glowing dog

Scientists genetically engineer glowing dog

In what’s maybe the most startling research I’ve been granted to read about recently, scientists from South Korea at Seoul National University, home to the world’s only strictly genetic engineering curricula, have successfully created a dog that can glow in the dark.

The genetically modified female beagle, named Tegon, was born in 2009 using a cloning technique which could help find cures for human diseases such as Alzheimer’s and Parkinson’s. Far from being a twisted joke, the whole experience can be marked as practice. By inserting genes into dogs that cause human illnesses and then swithiching these on and off, researchers are able to study them and come up with cures.

Glowing dog

(c) Genesis

The dog’s remarkable translucent ability was rendered possible after the South Korean scientists added eGFP (enhanced green flourescent protein) to the nucleus of a cell and placing it inside of an egg. The researchers, who completed a two-year test, said the ability to glow can be turned on or off by adding a drug to the dog’s food, called doxycycline.

“The creation of Tegon opens new horizons since the gene injected to make the dog glow can be substituted with genes that trigger fatal human diseases,” lead researcher Lee Byeong-chun said.

The same somatic cell nuclear transfer technology, which was used to create Tegon, was employed for the creation of Snoopy, the first cloned dog, in 2005 at the same university. Two years ago, the same scientists, produced Ruby Puppy, or Ruppy, a red-fluorescent-glowing dog.

The whole $3 million study can be read in detail at Genesis, the Journal of Genetics and Development.

reuters

Gene therapy for Parkinson disease boasts remarkable results

While gene-therapy is still regarded as a very innovative practice, it seems like the procedure might take traction as of today when remarkable results were concluded after the first successful double-blind gene therapy for Parkinson disease. In the case of this dreadful disease, medical researchers injected patients with a a gene that codes for glutamic acid decarboxylase (GAD), an enzyme that catalyses production of an inhibitory neurotransmitter called gamma-aminobutyric acid (GABA).

Usually Parkinson patients produce too little GABA in their brains, and as a result overstimulation in an area of the brain called the subthalamic nucleus occurs, which in turn inhibits dopamine secretion, which is vital for movement. This is why Parkinson patients are described as having tremors, sluggish movements, rigid muscles and impaired posture and balance.

Andrew Feigin of the Feinstein Institute for Medical Research in Manhasset, New York, and colleagues conducted a double-blind test for GAD gene-therapy on a group of 65 patients. In this particular case, double-blind test refers to the fact that patients were grouped into patients who received a placebo surgery (a simple saline solution injected in the back of the skull) and those receiving real surgery (the skull was drilled and a virus containing the GAD gene was injected). Neither patients, nor researchers knew who was given a placebo or not when test results came in, apart from the surgeons – hence the double-blind test.

In the trial, 22 Parkinson’s patients had a gene inserted in their brains to produce more GABA, while twenty-three patients received the placebo. Six months later, researchers analyzed the results and came up with something remarkable – gene therapy patients showed improvements in their motor functions of 23.1 per cent, while also remarkably interesting those who were given a sham procedure scored an improved of  just 12.7 per cent.  The researchers rated the patients’ symptoms, including the severity of tremors and stiffness, and came up with a single “motor score” that represented how well they could move.

The treatment is intended for a subgroup of Parkinson’s patients — those who do not respond to medication very well. Of the 1 million to 1.5 million Americans with Parkinson’s, about 10 to 15 percent of them, or 100,000 to 200,000 people, fit into this category, said study researcher Dr. Michael Kaplitt, vice chairman for research in the Department of Neurological Surgery at Weill Cornell Medical College in New York.

The therapy came just in time for Dr. Walter Liskiewicz, 60, a Jackson oral surgeon so disabled with Parkinson’s that he could not walk before his July 2009 procedure.Now, he not only walks with a cane but he’s back playing a harmonica and writing smooth jazz.

The study “brings us much closer to having a gene therapy that might be ready for general use,” Kaplitt said. The work paves the way for gene therapies for other types of brain diseases, he said. “I think we are now helping to facilitate and to accelerate the development of a whole host of gene therapies … for diseases such as Alzheimer‘s disease, epilepsy [and] depression,” he said.

The results are indeed very satisfying, but since the actual procedure was made only on 22 Parkinson patients, further investigation is required.

image via knowabouthealth.com

Bad science: injecting meth instead of ecstasy for trials

It never ceases to amaze me how this kind of idiotic, or perhaps even intentionally wrong studies are published and accepted by the world. What am I talking about ? Well, you know those pamphlets and promotional stuff that show your brain with holes in it when you take ecstasy, or that you will get Parkinson and all that ? It was based on a study which injected monkeys with ecstasy; only they didn’t inject them with ecstasy – they injected them with crystal meth ! Hey, and that’s not the only wrong thing here.

Crystal meth; do they look the same to you ?

The study published by the John Hopkins University was thankfully retracted, but the misinformational damage it caused is still in effect, despite the fact that there is no connection between ecstasy and Parkinson. Now, I’m not a drug advocate here, I can understand how two entirely different drugs can get mixed… by your local dealer, perhaps, who is a junkie himself. But to do this in a lab, and not any lab, but a John Hopkins lab – that’s downright criminal.

But wait, there’s more ! Not only did they inject the monkeys with meth, but they injected them with enormous quantities of it, every 3 to 9 hours ! This seems like a fairly good animal cruelty trial if you ask me, especially as 2 out of 3 monkeys dropped dead before they could be given their 3rd (!) dose. If you ask me, these findings would suggest that every 1 in 5 ecstasy users should drop dead pretty soon, right ? John Hopkins, of course, jumped in the defence of their research, but come on now. They injected the wrong drug; the dosage and timespan is absolutely nuts !

Read more about why this keeps happening here

Potential Alzheimer’s, Parkinson’s Cure Found In Century-old Drug

Every once in a while, you hear about the hardest of problems that have really easy solutions. In numerous cases, cures have been found in most common of substances, or even foods. This time, a study led by researchers at Children’s Hospital & Research Center Oakland showed that in small concentrations, something as common as methylene blue could significantly slow down or even cure Alzheimer’s and Parkinson’s disease.

This substance has been used for more than a century, in various situations, including as a treatment for a cold or a flu. The study was conducted by Hani Atamna, PhD, and a his team at Children’s and it was published in the March 2008 issue of the Federation of American Societies for Experimental Biology (FASEB) Journal.

Their research found that methylene blue can slow down or even prevent the decline of mitochondrial function, which leads to the above diseases.

“The results are very encouraging,” said Dr. Atamna. “We’d eventually like to try to prevent the physical and cognitive decline associated with aging, with a focus on people with Alzheimer’s disease. One of the key aspects of Alzheimer’s disease is mitochondrial dysfunction, specifically complex IV dysfunction, which methylene blue improves. Our findings indicate that methylene blue, by enhancing mitochondrial function, expands the mitochondrial reserve of the brain. Adequate mitochondrial reserve is essential for preventing age-related disorders such as Alzheimer’s disease.”

Methylene blue was first discovered more than 100 years from now, in 1891. It is used also for treating methemoglobinemia, a blood disorder. It is a well known fact that when taken in large quantities, it affects the brain. But what comes out as a surprise, at least to me, is that this fact alone was enough to discourage scientists to experiment with smaller quantities.