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Vaccine for Parkinson’s Disease Enters Phase 1 Clinical Trial
Copied from The Northwest Parkinson’s Foundation Weekly News Update
Katie Pratt
Brain Blogger - The word “vaccination” generally brings to mind the prevention of infectious disease. However, significant advances have recently been made in the field of therapeutic vaccination for the treatment of chronic human disorders including neurological conditions and cancer.
Simply put, a vaccine is a mixture of compounds (most often proteins) that are selected for their ability to activate the immune system. These compounds, also known as antigens, are then injected into the body where they prepare the immune system for a future assault. The result of such prophylactic vaccination is either complete immunity to the illness, or at least a significant reduction in disease severity.
While a prophylactic vaccine is administered as a preventative measure, therapeutic vaccines are intended to help fight a disease that has already taken root. For example, a therapeutic vaccine might be given to a patient with cancer in order to enlist the patient’s own immune system in the fight against the disease.
The problem with this kind of approach is ensuring that the antigen used in the vaccine does not induce an immune response against healthy parts of the body. Again, using cancer as an example, diseased cells often contain mutated proteins, or proteins that are not usually expressed in adult tissue (known as onco-fetal genes). This means that vaccines using these antigens specifically target cancer cells.
Recently, a therapeutic vaccine for Parkinson’s disease developed by Austrian pharmaceutical company Affiris entered a clinical trial, a landmark move in the management of a disease that is currently only treated at a symptomatic level.
Patients with Parkinson’s disease suffer from a number of debilitating symptoms that are the result of the loss of a particular class of neurons in the brain. These neurons are involved in the control of muscle function and are particularly sensitive to the neurotransmitter dopamine. It is for this reason that current treatments revolve around modulation of the levels of this chemical.
The underlying molecular cause of the disease is a protein called alpha-synuclein. Ordinarily this protein is found throughout the neocortex, hippocampus, thalamus, substantia nigra, and cerebellum, although its precise function remains unknown. Importantly, this protein is very unusual in that it does not fold up like the majority of proteins. Its “floppy”, unfolded appearance means that it is particularly susceptible to getting tangled up and forming protein aggregates within brain cells, thus sentencing the affected cell to death. The formation of protein aggregates also underlies other brain disorders, including Alzheimer’s disease and Creutzfeld-Jacob disease.
It is the alpha-synuclein protein tangles that are targeted by the vaccine currently in trials, PD01A. The study, funded by the Michael J. Fox Foundation to the tune of $1.5 million, will assess the safety of the vaccine in both men and women with Parkinson’s disease, with the results expected in July of 2014.
Given the prevalence of protein aggregates in brain diseases, therapeutic vaccination might therefore represent a promising future treatment for several neurological conditions.
http://brainblogger.com/2012/09/14/vaccine-for-parkinsons-disease-enters-phase-1-clinical-trial/
Procedure Could Help Local Patients Beat Parkinson's Disease
Copied from The Northwest Parkinson’s Foundation Weekly News Update
Chris Chan
NBC 7 San Diego - Researchers hope a procedure using patients' own stem cells will cure Parkinson's Disease, or at least eliminate symptoms for decades.
Eight patients have joined the project at Scripps Research Institute in La Jolla to take part in the initial trial. Before they are able to proceed, they must get funding and obtain approval from the Food and Drug Administration.
"We're all treading water until the funds can be found and the hoops that the FDA give us can be jumped through," said Cassandra Peters, who was a paralegal at a law firm until 2005, when the symptoms of Parkinson's made it too difficult to work. She was diagnosed at age 44, 13 years ago.
The planned procedure entails taking a skin sample from the patients, then creating pluripotent stem cells with the genetic material. Millions of stem cells will then be injected into the brain to create dopamine neurons, which are destroyed by Parkinson's disease.
It's a technique discovered by Japanese researcher Shinya Yamanaka who won the Nobel Prize in Medicine in 2012.
Jeanne Loring, Ph.D., Director of the Center of Stem Cell Research at the Scripps Research Institute said similar work has been done in the past.
"There was work done in the 1980s and early 1990s in which fetal tissue was transplanted into the brains of people with Parkinson's disease," Loring said.
She said the problem was that fetal tissue produced inconsistent results.Loring believes using pluripotent stem cells derived from the same patient in which the cells will be transplanted will be much more reliable.
"The thing about Parkinson's Disease is there's really only one nerve cell type that needs to be replaced, and we know exactly where to put it," Loring said.
That confidence has been passed to the patients in this project who, unlike many other research projects, have been very involved in the process-- meeting with scientists and researchers in the laboratory.
"If this procedure works, and I know that it will, it will be the answer to so many people's prayers," Peters said.
Funding for the procedure remains a challenge as the government has not provided any grants for the project. Patients have been taking matters into their own hands, raising money for the non-profit Summit 4 Stem Cell, which hopes that Parkinson's victims' hike to Mount Everest base camp can help raise money for this initial procedure.
Edward Fitzpatrick, who was diagnosed with Parkinson's nearly seven years ago, said the group has raised nearly one million dollars and needs to raise $1.5 million more to perform the procedure on the initial test group.
The Food and Drug Administration must also give its approval. Dr. Loring said there were no set requirements from the regulatory group, but researchers are working closely with the FDA to reach a solution.
Mentor Fulbright Scholar to study way to treat Parkinson's disease
Copied from The Northwest Parkinson’s Foundation Weekly News Update
Janet Pokolak
News-Herald of Northern Ohio - One day Patrick Chirdon's name may be linked with a cure for Parkinson's disease, which today affects about 3 percent of the older population.
The Mentor man, who recently graduated with honors from Case Western Reserve University in Cleveland, is off to Switzerland next month as a Fulbright Scholar to continue research he began in Northeast Ohio.
Chirdon found evidence that a thyrotropin-releasing hormone, called TRH, protects brain cells in a way that could make it an effective treatment against Parkinson's disease.
But it's the mice in Switzerland, not its storied scenery, that has excited Chirdon the most. The laboratory where he'll work is the Brain Mind Institute at the Ecole Polytechinque Federale de Lausanne (Swiss Federal Institute of Technology in Lausanne) — the only one in the world to develop a laboratory rat with a gene specific to his area of study.
"Their rat model is the only one to have the specific gene mutation (LRRK2) that's recognized as the most common genetic cause of Parkinson's," he said.
"I've come to the conclusion that drugs based on a structure of thyrotropin-releasing hormone may inhibit the LRRK2 enzyme and be an effective treatment for Parkinson's. It is my intent to study to effects of these drugs on these animals."
It's something that would need to be done before clinical trials with humans could be done, he said.
"And this is the only place in the world where it is possible."
His research at CWRU found that TRH helped to regrow neurons and minimize cell death in a brain region, known as the striatum, that is heavily affected by Parkinson's. The cell death of dopamine neurons leads to some of the motor symptoms of Parkinson's, he said.
The hormone is known primarily for affecting thyroid metabolism, but Chirdon found mounting evidence in spinal muscular atrophy and epilepsy that it helped protect neurons against toxicity and stressors. But the evidence was a review of literature, and the reality is what he needs to test in mice.
He first became interested in how the thyrotropin-releasing hormone works while working in the lab of the late Mark A. Smith, a professor of pathology and director of basic science research of the University Memory and Cognition Center. Smith, who was dedicated to teaching and mentoring students, infected Chirdon with his passion for science and pushed him to think critically.
"My inspiration for this project came directly from Dr. Smith," Chirdon said. "He had a huge impact on my career choice."
Because Chirdon's grandfather had Alzheimer's disease, his early studies went in that direction — another area of expertise for Smith.
In fact, Chirdon worked in Smith's Alzheimer's pathology lab at Case as well as the labs of Dr. Kingman Stohl and Dr. Pingfu Feng at the Veterans Affairs Hospital.
"I used human brain samples from Alzheimer's patients and age-matched controls to analyze thyrotropin-releasing hormone concentration in various brain regions," he said.
But after Smith was struck by a car and killed in December 2010, Chirdon no longer had a lab for his research. But his dedication didn't end.
He spent last summer studying in Baltimore with Dr. Bronwen Martin at the National Institutes of Health. As his research mentor, she invited Chirdon to be first author on a paper that proposes using thyrotropin-releasing-hormone-based drugs for Parkinson's disease treatment. It would serve as an alternative to the current treatment, which sometimes results in painful muscle spasms.
Not only was the paper submitted to the journal Current Alzheimer's Research, it also went to the Brain Mind Institute at the Swiss Federal Institute of Technology, Lausanne, as part of his application for a Fulbright Scholarship.
In her letter of recommendation to the Fulbright Program Selection Committee, Martin cited Chirdon's resourcefulness.
"He even translated some very relevant papers that were only available in Japanese," she wrote.
After graduating in 2008 from Mentor High School, Chirdon went to Case to study psychology. But it is the biology of the brain that has captured his interest. He hopes to go on to earn a doctorate degree in pathology but is leaving himself open for his year in Switzerland to help him further fine-tune his focus.
"It was determined that the TRH project would take longer than a year to complete and would cost more than I had requested from the Michael J. Fox Foundation, so it might be better for me to save it as a Ph.D. dissertation," he said.
Dr. Patrick Aebischer, one of a pair of doctors who will oversee Chirdon's work in Switzerland, said Chirdon will be able to use animal models with neurodegenerative diseases to investigate how pathology interacts with genes involved in the process of brain aging.
"During his stay in my laboratory, Mr. Chirdon will have full access to all available equipment," Aebischer wrote in his Fulbright Scholarship letter of affiliation. "A personal lab space, including a desk, will be provided, and Mr. Chirdon will be accredited as a member of the EPFL, which offers various activities on the campus."
That affiliation will allow him to explore Switzerland and nearby France in his free time. But for the next year he doesn't expect to have much in the way of free time.
The study I propose will take a year to complete working full-time," he said. "It helps that I speak German and have a working knowledge of French."
He said middle-aged rats — 17 months old — will be used because the thyrotropin-releasing hormone expression varies with age. Behavioral effects will be evaluated by using tests for motor activity.
"Aging research, which I am primarily interested in, is especially significant in Switzerland because of all the countries in Europe, it has the most people 100 years old and older," he said.
He's learned that 15,000 people in Switzerland are living with Parkinson's and hopes this research can help build a bridge between the U.S. and Switzerland with this collaboration.
In America, more than 50,000 cases of Parkinson's are diagnosed each year.
http://new
Researchers say Parkinson's cure may lie in the human nose
Copied from The Northwest Parkinson’s Foundation, Weekly News Update
Laura Ungar
USA Today - University of Louisville researchers hoping to find a cure for Parkinson's disease have discovered an unlikely potential treatment — stem cells from the human nose.
Videos from a laboratory at Louisville reveal the promise: One shows a rat with a brain damaged to mimic Parkinson's continually circling the bottom of a bowl in one direction, unable to do anything else. Another shows a similar rat injected with nasal stem cells moving normally and trying to climb out.
The research — which uses an adult patient's own cells — is outlined in this month's issue of the journal Stem Cells Translational Medicine.
"I think it would be wonderful to have thought of something … that could help people. That's what I'm in this for," said Louisville neuroscientist Fred Roisen, chief science officer and co-founder of a company based on the technology called RhinoCyte.
Parkinson's — which afflicts about a million Americans, including Louisville-born boxing legend Muhammad Ali— is a progressive neurological disorder that mostly strikes people over 50, causing tremors, slow movement and other problems.
It occurs when nerve cells in the brain that produce dopamine, a chemical that helps control muscle movement, are slowly destroyed.
It "is a terrible disease," Roisen said. "And as our population ages, there are gonna be more and more people with Parkinson's."
John Baumann, a 51-year-old Shelby County man diagnosed with it a decade ago, said he finds the research "interesting and coincidental" because his sense of smell was the first thing to go when he began developing Parkinson's. Loss of smell is considered an early warning sign.
"Anything that could lead to a cure is wonderful news," said the lawyer, author and inspirational speaker. "Stem cells have always scared me, since there's so much opportunity for something to go wrong. But when it's done in a moralistic and disease-related way, I'm all for it."
Spurring improvement
Roisen said nasal stem cells are not a cure for Parkinson's but do seem to spur improvement in some research animals. The study says about 35% of rats getting the cells experienced "improved behavioral recovery."
But Scott Whittemore, a stem cell researcher and vice chairman for research in the Department of Neurological Surgery at Louisville, pointed out that about two-thirds of the rats getting nasal stem cells didn't experience recovery.
"This is an intriguing initial study," said Whittemore, who was not involved in the research. "But the success rate needs to be increased before it would be a potentially viable therapeutic option."
There are medicines to treat Parkinson's symptoms, but they don't stop the progression of the disease.
Baumann said he takes medication but still suffers from fatigue and hand tremors and would love to take advantage of a more permanent treatment.
In Roisen's research, he uses a tiny bit of tissue from the olfactory neurosensory epithelium, removed during outpatient surgery from a nickel-sized region high in a nasal passage that's responsible for the sense of smell. The procedure doesn't harm the patient's ability to smell.
Roisen said these cells are unique, regenerating themselves every 30 to 60 days.
"Stem cells are there to replenish lost or damaged cells," he said. "The excitement is, you can use a stem cell to replace damaged or lost cells in the body."
After the tissue is removed, it's grown for six to 10 weeks, after which progenitor cells, or specialized cells with a tendency to turn into neural cells, are isolated and grown.
The cells are then injected during surgery into the brain region affected by Parkinson's. Or, they are frozen for future use.
Roisen said nasal stem cells have advantages over other types of cells -- including the fact that they don't carry the moral and scientific baggage of embryonic stem cells, which are from human embryos and have the potential to cause tumors. And since nasal stem cells come from the patient, no anti-rejection drugs are needed.
Twenty-four weeks after getting the cells, about 35% to 40% of rats with Parkinson-like symptoms demonstrated not only behavioral recovery but also "better mobility and coordination," Roisen wrote in a paper on the research. "In contrast, the animals receiving no (nasal stem cells) or a cellular control group showed no significant improvement."
Human trials in 2014
Roisen said he's excited about the research on nasal stem cells, and is stepping down as chairman of university's Department of Anatomical Sciences and Neurobiology at the end of the month to devote more time to it.
He and his team are also studying the use of nasal stem cells to treat spinal cord injury; they announced results of that research in 2006.
If everything goes well, Roisen said human clinical trials involving people with spinal cord injuries could begin next year, and human clinical trials involving Parkinson's patients could begin in 2014. Roisen said the treatment could become widely available by 2019 or even before.
Steve Gailar, acting chief executive officer of RhinoCyte, said Roisen's research has been funded since 2006 with about $4.5 million from investors, including venture firms and the University of Louisville Foundation.
He said the company is now trying to raise $10 million to take it through early stage clinical trials for spinal cord injury and to enter into the first early-stage human trials for Parkinson's.
Joy Cavagnaro, a consultant to RhinoCyte on regulatory matters, said she's not aware of any other scientists working on using nasal stem cells in this way.
She said it may be easier for Roisen to gain popular support than scientists working with embryonic stem cells, since the nasal cells don't have the same potential for creating tumors and don't raise the ethical and religious issues embryonic cells do.
Whittemore agreed that nasal stem cells have benefits but he said cell therapies in general "are still not the first option for Parkinson's." Symptomatic treatments such as medicines or surgical deep brain stimulation remain higher on the list.
And while the recent study shows potential for nasal stem cells, Whittemore said, "that's still a ways off from being a therapy."
http://www.usatoday.com/news/health/story/2012-06-23/parkinsons-cure-human-nose/55787500/1
Parkin gene researchers grow Parkinson's brain cells in lab
Copied from The Northwest Parkinson’s Foundation Weekly News Update
George Frodsham
Bio News - Human brain cells with Parkinson's disease have been successfully grown in a Petri dish, allowing researchers to study them in unprecedented detail. American researchers used a technique in which human skin cells are transformed into induced pluripotent stem (iPS) cells, which can then be made to change into any cell type - in this case, neurons.
In the study, published in Nature Communications, skin cells were taken from two healthy donors and from two patients with a strain of Parkinson's disease that is caused by a mutation in the parkin gene. The neurons that resulted from the patients' skin cells possessed the same parkin mutation. The mutation is known to be the cause of the disease in about ten percent of Parkinson's patients; the cause in the remaining 90 percent of cases is unknown.
The work enabled the group to see how the parkin mutation causes Parkinson's. It will also allow researchers to investigate, up close, the effects of potential new treatments, and study other neurodegenerative diseases by observing neurons directly.
Study leader Dr Jian Feng, from the University at Buffalo in New York, said that this was the first time that brain cells had been generated from Parkinson's patients with parkin mutations: 'Before this, we didn't even think about being able to study the disease in human neurons. The brain is so fully integrated. It's impossible to obtain live human neurons to study'.
The parkin gene normally helps the brain control the levels of dopamine, a brain signalling chemical. When a mutation occurs an enzyme called monoamine oxidase (MAO), which is toxic to dopamine-producing cells, is produced uncontrollably, thereby killing neurons and causing Parkinson's disease.
'We found that when parkin is mutated, that regulation [of MAO] is gone, so MAO is [produced] at a much higher level', said Dr Feng. 'The nerve cells from our Parkinson's patients had much higher levels of MAO expression than those from our controls'.
Dr Feng said he hopes that the work will help further understanding of Parkinson's disease and develop new treatments: 'We suggest in our study that it might be possible to design a new class of drugs that would dial down the expression level of MAO'.
Note by John Pepper
I would assume, from the above article, that MAO-b inhibitors might only work on patients who have this particular gene mutation. This might explain why MAO-b inhibitors work for some patients and not for others. I am not a medical person, so don’t take this as fact. It is my conjecture.
Obama plans push to map brain
Copied from The Northwest Parkinson’s Foundation Weekly News Update
President Obama will announce a $100 million initiative to map human brain circuits in research that could lead to treatments for such conditions as Alzheimer’s, epilepsy and traumatic brain injury.
JAMES GORMANJOHN MARKOFF
Seattle Times - President Obama on Tuesday will announce a broad new research initiative, starting with $100 million in 2014, to invent and refine new technologies to understand the human brain, senior administration officials said Monday.
A senior administration scientist compared the new initiative to the Human Genome Project, in that it is directed at a problem that has seemed insoluble up to now: the recording and mapping of brain circuits in action in an effort to “show how millions of brain cells interact.”
The effort will require the development of new tools not yet available to neuroscientists and, eventually, perhaps lead to progress in treating conditions like Alzheimer’s, epilepsy and traumatic brain injury. It will involve both government agencies and private institutions.
The initiative, which scientists involved in promoting the idea have been calling the Brain Activity Map project, will officially be known as Brain Research Through Advancing Innovative Neurotechnologies, or BRAIN for short; it has been designated a grand challenge of the 21st century by the Obama administration.
Three government agencies will be involved: the National Institutes of Health (NIH), the Defense Advanced Research Projects Agency and the National Science Foundation.
A working group at the NIH, described by the officials as a “dream team,” and led by Cori Bargmann of Rockefeller University and William Newsome of Stanford University, will be charged with coming up with a plan, a time frame, specific goals and cost estimates for future budgets.
Brain researchers can now insert wires in the brains of animals, and sometimes human beings, to record the electrical activity of brain cells called neurons, as they communicate with each other. But, Newsome said, they can record at most hundreds at a time.
New technology and new theoretical approaches would need to be developed to record thousands or hundreds of thousands of neurons at once, Newsome said.
Now the beauty of stem cells is only skin deep
17 May 2013 00:00 - Sarah Wild
A new stem cell technique could re-grow organs that the body will not reject and is an important step towards a cure for diseases such as Alzheimer's.
It is "incredibly exciting", says Professor Michael Pepper, director of the Institute for Cellular and Molecular Medicine at the University of Pretoria, adding that it is not a question of "whether the technology comes to South Africa, but when".
Scientists at the Oregon Health & Science University and the Oregon National Primate Research Centre on Wednesday announced in a joint press release that they had succeeded in "[reprogramming] human skin cells to become embryonic stem cells capable of transforming into any other cell type in the body".
This means that the stem cells – used for therapeutic rather than reproductive purposes – contain the same genetic matter as the person they are being put into and will not be rejected, says lead researcher Shoukhrat Mitalipov.
It is based on a technique called somatic cell nuclear transfer (SCNT), which involves transplanting the nucleus of one cell, with the donor's DNA, into an egg cell that has had its nucleus removed. The Oregon-based researchers used unfertilised eggs.
Although SCNT is not new, stem cell specialist at the
Genetic material
Pepper distinguishes between adult stem cells and pluripotent stem cells, which include induced pluripotent stem cells (iPSCs), which are cells that can also be manipulated into becoming liver cells or heart cells, for example. John Gurdon of the Gurdon Institute in
Although iPSCs offer "huge therapeutic potential, the technology involves the introduction of new genes into the cell to make them pluripotent", Pepper says.
The difference between SCNT and this new technique is that the American researchers have generated primitive stem cells that have the genetic material of the donor, and therefore, because the donor and the recipient are the same person, the cells will not be rejected.
According to the researchers and South African experts, this new technique is important for two reasons: it uses a patient's genetic material – so it will not be rejected, which can happen if another person's DNA or cells are involved in the process – and it does not use a fertilised egg or an early embryo, thus removing concerns about the ethics surrounding the origin of the cells.
Mitalipov also notes that it is unlikely that this technique would be able to be used for reproductive, rather than therapeutic, cloning. Human cloning is illegal in most countries in the world.
When asked whether South Africans would see this technology, Pepper says: "We see everything in
"A drawback is that the technology is not simple – but that's not a long-term problem. It gets easier as it develops."
SOURCE : http://mg.co.za/article/2013-05-17-00-now-the-beauty-of-stem-cells-is-only-skin-deep
New drug protects neurons in Parkinson's patients
Copied from The Northwest Parkinson’s Foundation Weekly News Update
Scientists at Emory University School of Medicine have identified a compound that boosts levels of a survival factor in neurons threatened by Parkinson's disease.
Medical Press - The compound, bis-3-cognitin, could be a starting point for finding drugs that delay Parkinson's disease progression. Bis-3-cognitin appears to protect mitochondria, critical sites of vulnerability for neurons affected by Parkinson's.
In a widely used animal model of Parkinson's, bis-3-cognitin could protect neurons from damaging toxins and prevent mice from developing motor problems when it was given together with the toxin. The results were published online August 13 by the Journal of Biological Chemistry.
Zixu Mao, professor of pharmacology and neurology at Emory University School of Medicine, and his colleagues had been studying MEF2D, a protein that is vital for the survival of neurons. The first author of the paper, graduate student Lu Yao, is now at Xi'an Jiaotong University in China. Collaborators include Yifan Han and his colleagues at Hong Kong Polytechnic University.
Mao's previous research had shown that MEF2D is perturbed in the neurons of people with Parkinson's disease. The MEF2D protein is sensitive to cellular changes, such as oxidative stress, which can lead to neuron damage in Parkinson's.
"For years, we had been talking about looking for drugs that enhance MEF2D," Mao says. "The challenge was how to set up a screening system. You can search through a library of small molecules, or you can look through the literature and make a guess."
Bis-3-cognitin appears to have been a good guess, even though it was originally developed for a different purpose. The cognitins are a family of compounds derived from tacrine, the first drug approved by the FDA to treat the symptoms of Alzheimer's disease. Tacrine was eventually discontinued because of liver toxicity and other side effects. The bis-cognitins have two tacrine molecules connected by a flexible chain.
Bis-3-cognitin could protect cells in culture against damage coming from the toxin MPTP, which mimics the effects of Parkinson's, by increasing MEF2D levels in the cells' nuclei and mitochondria. Tacrine and bis-7-cognitin, which has a longer connecting chain than bis-3-cognitin, did not have the same effects.
MPTP kills dopamine-responsive neurons, which are the same cells affected in Parkinson's. In mice, the scientists gauged the toxin's behavioural effects by measuring how long mice were able to hang on to a rotating rod, and studying their gait. Bis-3-cognitin, when given together with MPTP, could prevent motor impairment in the mice.
"We think MEF2D is not the only target of bis-3-cognitin," Mao says. "It is a potent antioxidant, for example. But MEF2D is required for the neuroprotective activity—we found that if you knock down MEF2D in cell lines, the protective effects are much weaker."
He adds that bis-3-cognitin appears to avoid the acute toxicity problems of tacrine, but more pharmacological studies of bis-3-cognitin's properties and mode of action are needed before human clinical trials.
More information: L. Yao et al. Activation of transcription factor MEF2 by bis(3)-cognitin protects dopaminergic neurons and ameliorates Parkinsonian motor defects. J. Biol Chem. (2012). www.jbc.org/cgi/do… .M112.367540 Journal reference: Journal of Biological Chemistry Provided by Emory University
Drug for Parkinson’s comes closer to reality
Copied from The Northwest Parkinson’s Foundation Weekly News Update
OHSU Brain Institute
Indian Express - Researchers at Lund University in Sweden have shed light on how Parkinson’s disease spreads through the brain.
Experiments in rat models uncover a process previously used to explain mad cow disease, in which misfolded proteins travel from sick to healthy cells.
This model has never before been identified so clearly in a living organism, and the breakthrough brings researchers one step closer to a disease-modifying drug for Parkinson’s.
“Parkinson’s is the second most common neurodegenerative disorder after Alzheimer’s disease,” said Patrik Brundin M.D., Ph.D., Jay Van Andel Endowed Chair in Parkinson’s Research at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University and senior author of the study.
“A major unmet medical need is a therapy that slows disease progression. We aim to better understand how Parkinson’s pathology progresses and thereby uncover novel molecular targets for disease-modifying treatments,” he stated.
Previous research demonstrates that a misfolded protein known as alpha-synuclein protein gradually appears in healthy young neurons transplanted to the brains of Parkinson’s patients. This discovery gave rise to the group’s hypothesis of cell-to-cell protein transfer, which has since been demonstrated in laboratory experiments.
In the current study, researchers for the first time were able to follow events in the recipient cell as it accepts the diseased protein by allowing it to pass its outer cell membrane. The experiments also show how the transferred proteins attract proteins in the host cell leading to abnormal folding or “clumping” inside the cells.
“This is a cellular process likely to lead to the disease process as Parkinson’s progresses, and it spreads to an increasing number of brain regions as the patient gets sicker,” said Elodie Angot, Ph.D., of Lund University’s Neuronal Survival Unit, and lead co-author of the study.
“In our experiments, we show a core of unhealthy human alpha-synuclein protein surrounded by alpha-synuclein produced by the rat itself. This indicates that this misfolded protein not only moves between cells but also acts as a “seed” attracting proteins produced by the rat’s brain cells,” said Jennifer Steiner, Ph.D., of Lund University and Van Andel Institute’s Center for Neurodegenerative Science, the study’s other lead author.
These findings are consistent with results from previous laboratory cell models and for the first time extend this observation into a living organism. However, it remains unclear exactly how alpha-synuclein gains access from the extracellular space to the cytoplasm of cells to act as a template for naturally occurring alpha-synuclein, causing the naturally-occurring protein to, in turn, misfold. Further studies are needed to clarify this important step in the process.
The discovery does not reveal the root of Parkinson’s disease, but in conjunction with disease models developed by Lund University researchers and others, could enable scientists to develop new drug targets aimed at mitigating or slowing the effects of the disease, which currently strikes more than 1percent of people over the age of 65.
The findings were published this week in the Public Library of Science (PLoS) One.
http://www.indianexpress.com/news/drug-for-parkinsons-comes-closer-to-reality/968324/2
MSU researchers identify path to treat Parkinson’s disease at its inception
Copied from Northwest Parkinson’s Foundation Newsletter
Yujie Chen, MSU graduate student, was one of the co-authors of the paper
Michigan State University - Imagine if doctors could spot Parkinson’s disease at its inception and treat the protein that triggers it before the disease can sicken the patient.
A team of researchers led by Basir Ahmad, a postdoctoral researcher at Michigan State University, has demonstrated that slow-wriggling alpha-synuclein proteins are the cause of aggregation, or clumping together, which is the first step of Parkinson’s. The results are published in the current issue of the Proceedings of the National Academy of Sciences.
Proteins, which are chain molecules composed of amino acids, do most of the work in cells. While scientists understand how proteins are structured, they do not yet know how they are built – a process known as folding. When errors happen in folding, proteins clump together, form plaques such as those found in Parkinson’s disease, Alzheimer’s and Lou Gehrig’s disease, and cause cells to degenerate.
Lisa Lapidus, MSU associate professor of physics and astronomy and co-author of the paper, has dedicated her lab to researching folding. Using lasers to investigate the protein alpha-synuclein, the scientists correlated the speed at which the protein rearranges with its tendency to clump. A slower speed places the protein in a “dangerous regime,” a pace that allows it to develop sticky patches, aggregate and cause cellular damage, Lapidus said.
“There are many, many steps that take place in aggregation, but we’ve identified the first step,” she said. “Finding a method to fight the disease at its first stage, rather than somewhere further down the road, can hopefully increase the success rate in which the disease is treated.”
The identification of this critical first step already has the researchers pursuing new ways to attack the disease. Lapidus is currently testing a number of naturally occurring compounds, such as curcumin, ECGC and resveratrol, which could push the rearranging protein out of the danger zone.
“We are now looking for molecules that can alter the protein when it first begins to ‘misfold,’ which could eventually lead to the development of a drug that could prevent aggregation before it happens,” she said.
http://news.msu.edu/story/10212/
Cure for Alzheimer's and Parkinson's disease a step closer
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TVNZ - New Zealand scientists have made a breakthrough in stem cell research, taking a cure for Alzheimer's and Parkinson's disease one step closer.
While the study has found what is preventing some stem cells from becoming neurons, scientists at Auckland's University Centre for Brain Research have pinned down the culprit at a cellular level.
They found that stem cells have to move around the brain to find their place in order to produce a coat of slippery molecules to make it easy to move.
Once in place, they absorb the slippery layer and become neurons, connecting with other neurons to form circuits.
"It's a little bit like putting soap on yourself before you go down a hydro slide, it makes the journey a lot less friction filled," Dr Maurice Curtis from the Centre for Brain Research said.
"The cells do a similar thing. But when they get to the right location they need to be able to remove that slippery coating in order to stop and intergrate to form networks."
In brains with diseases like Alzheimer's and Parkinson's, the slippery coat stays on the outside of the cell which makes it hard to become a neuron and to connect with others.
The study has found that an oversupply of insulin stops the cell re-absorbing the slippery molecules.
"We know, for instance that high levels of insulin block the process of removing the slippery coating. We think will actually increase the re-absorbtion which may have significant implications for getting brain cells to connect up better," Dr Curtis said.
Link between allergic rhinitis and Parkinson’s disease
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Kriss Moore
The Almagest - People who have allergic rhinitis have three times the risk of Parkinson’s disease. Previous research has shown that those taking non-steroidal anti-inflammatory drugs, like ibuprofen, are less likely to develop Parkinson’s disease. So researchers at the Mayo Clinic set out to find out more about a possible link between inflammation and Parkinson’s disease. They studied 196 people who had Parkinson’s disease and compared them with a group of similar age and gender who did not.
Those with allergic rhinitis – or hayfever, an inflammatory condition – were 2.9 times more likely to develop Parkinson’s disease. But no similar link was seen for other inflammatory diseases like lupus, rheumatoid arthritis or vitiligo. This may be because there were only small numbers of participants who had these conditions. The researchers say that those with allergic rhinitis exert an immune response to allergens which could affect the brain, leading to Parkinson’s disease. The study does not establish that allergies cause Parkinson’s disease, just that there is an association. Hopefully future research will lead to ways of blocking any inflammation that does cause Parkinson’s disease.
The Pharmaceutical Industry
For an interesting assessment on the pharmaceutical industry, click on this link
This message is a well put-together account of the Pharmaceutical Industry's attitude towards 'Health-care'. Listen carefully to it. It is the message that my book has been preaching to Pd sufferers for the past eight years. This was my opinion of the industry, for what it was worth. It it is not in the interests of the pharmaceutical industry to look for a cure for any illness or disease. If they come up with a cure for anything, their income from treating that particular condition would soon disappear.
This is perfectly understandable and cannot be legislated against. It is also possible, and highly probable that many companies in the industry have purchased patents for many cures, in order to see that they do not get onto the market and ruin their business. This is also not illegal and is perfectly understandable.
My book is my own personal account of what I have been able to do to reverse my Pd symptoms. I stress that I have not been cured of my Pd, but have managed to reduce its effects to the level at which I am able to live a normal life, no worse than anybody else who has not got Pd.
Interesting studies were carried out by a company by the name of Amgen. If you Google, ‘Amgen GDNF’, you will read about their studies on this naturally occurring substance. This substance is produced in the body, when we do certain types of energetic exercise. For some reason, they stopped this project, even though the first study, which was successfully carried out on a small number of patients, showed a good result for all or most of the patients. It would be interesting to know for certain the real reason why this project was discontinued?
My Pd symptoms started in the early 1960's, possibly 1963, but I was only diagnosed with Pd, twenty-nine years later, in 1992, and I have been doing regular energetic exercise ever since 1970. I am now 78 years of age and still look forward to many more years of useful life, God willing.
Certain types of energetic exercise have been clinically proven to produce Glial Derived Neurotrphic Factor, (GDNF) - as mentioned in the trials done by Amgen - in the brain, which is capable of repairing the damaged brain cells. This gives some idea why it took twenty-five years, after the first symptom appeared, for my Pd to be diagnosed. The exercise was obviously affectively reversing the Pd at a rate that was almost as fast as the Pd was progressing.
When the exercise was joined in 1992 by the intake of an MAO-b inhibitor, my symptoms started to improve. Ten years later, in 2002, nobody would ever have known that I still had Pd!
I am thankful for having had the good fortune to have been forced to do energetic exercise, early on in my life. God works in funny ways, what he takes away in the one hand, he gives back in the other. If you don't believe in God, maybe I should have used the word, 'Creation'. The human race could not have survived if we were not supplied with the ability to overcome injuries and natural health problems.
Why did Amgen decide to spend large sums of money on producing an artificial form of GDNF, when our bodies can produce this substance, quite naturally, when we do certain types of energetic exercise? This beats me!
Some of us may not like doing exercise, but it is better than the alternative. Your health is really in YOUR OWN HANDS! Don't give it away to someone else to control.
It is my opinion that the chances of a cure for Parkinson's, or any other neurological condition, coming onto the market in the foreseeable future, is very slim! I am not being negative about this, but unless people and organisations, outside of the pharmaceutical Industry, look for the elusive cure, it will never happen!
Why not order your very own copy of my book
Reverse Parkinson’s Disease!
For easy Ordering: Go to my Website
It will be the best money you have ever spent!
Obama plans push to map brain
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President Obama will announce a $100 million initiative to map human brain circuits in research that could lead to treatments for such conditions as Alzheimer’s, epilepsy and traumatic brain injury.
JAMES GORMANJOHN MARKOFF
Seattle Times - President Obama on Tuesday will announce a broad new research initiative, starting with $100 million in 2014, to invent and refine new technologies to understand the human brain, senior administration officials said Monday.
A senior administration scientist compared the new initiative to the Human Genome Project, in that it is directed at a problem that has seemed insoluble up to now: the recording and mapping of brain circuits in action in an effort to “show how millions of brain cells interact.”
The effort will require the development of new tools not yet available to neuroscientists and, eventually, perhaps lead to progress in treating conditions like Alzheimer’s, epilepsy and traumatic brain injury. It will involve both government agencies and private institutions.
The initiative, which scientists involved in promoting the idea have been calling the Brain Activity Map project, will officially be known as Brain Research Through Advancing Innovative Neurotechnologies, or BRAIN for short; it has been designated a grand challenge of the 21st century by the Obama administration.
Three government agencies will be involved: the National Institutes of Health (NIH), the Defense Advanced Research Projects Agency and the National Science Foundation.
A working group at the NIH, described by the officials as a “dream team,” and led by Cori Bargmann of Rockefeller University and William Newsome of Stanford University, will be charged with coming up with a plan, a time frame, specific goals and cost estimates for future budgets.
Brain researchers can now insert wires in the brains of animals, and sometimes human beings, to record the electrical activity of brain cells called neurons, as they communicate with each other. But, Newsome said, they can record at most hundreds at a time.
New technology and new theoretical approaches would need to be developed to record thousands or hundreds of thousands of neurons at once, Newsome said.
MIT scientists model structure of alpha synuclein protein associated with Parkinson's
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Computer modelling may resolve conflicting results and offer hints for new drug-design strategies
news-medical.net - Clumps of proteins that accumulate in brain cells are a hallmark of neurological diseases such as dementia, Parkinson's disease and Alzheimer's disease. Over the past several years, there has been much controversy over the structure of one of those proteins, known as alpha synuclein.
MIT computational scientists have now modeled the structure of that protein, most commonly associated with Parkinson's, and found that it can take on either of two proposed states - floppy or rigid. The findings suggest that forcing the protein to switch to the rigid structure, which does not aggregate, could offer a new way to treat Parkinson's, says Collin Stultz, an associate professor of electrical engineering and computer science at MIT.
"If alpha synuclein can really adopt this ordered structure that does not aggregate, you could imagine a drug-design strategy that stabilizes these ordered structures to prevent them from aggregating," says Stultz, who is the senior author of a paper describing the findings in a recent issue of the Journal of the American Chemical Society.
For decades, scientists have believed that alpha synuclein, which forms clumps known as Lewy bodies in brain cells and other neurons, is inherently disordered and floppy. However, in 2011 Harvard University neurologist Dennis Selkoe and colleagues reported that after carefully extracting alpha synuclein from cells, they found it to have a very well-defined, folded structure.
That surprising finding set off a scientific controversy. Some tried and failed to replicate the finding, but scientists at Brandeis University, led by Thomas Pochapsky and Gregory Petsko, also found folded (or ordered) structures in the alpha synuclein protein.
Stultz and his group decided to jump into the fray, working with Pochapsky's lab, and developed a computer-modeling approach to predict what kind of structures the protein might take. Working with the structural data obtained by the Brandeis researchers, Stultz created a model that calculates the probabilities of many different possible structures, to determine what set of structures would best explain the experimental data.
The calculations suggest that the protein can rapidly switch among many different conformations. At any given time, about 70 percent of individual proteins will be in one of the many possible disordered states, which exist as single molecules of the alpha synuclein protein. When three or four of the proteins join together, they can assume a mix of possible rigid structures, including helices and beta strands (protein chains that can link together to form sheets).
"On the one hand, the people who say it's disordered are right, because a majority of the protein is disordered," Stultz says. "And the people who would say that it's ordered are not wrong; it's just a very small fraction of the protein that is ordered."
The MIT researchers also found that when alpha synuclein adopts an ordered structure, similar to that described by Selkoe and co-workers, the portions of the protein that tend to aggregate with other molecules are buried deep within the structure, explaining why those ordered forms do not clump together.
Stultz is now working to figure out what controls the protein's configuration. There is some evidence that other molecules in the cell can modify alpha synuclein, forcing it to assume one conformation or another.
"If this structure really does exist, we have a new way now of potentially designing drugs that will prevent aggregation of alpha synuclein," he says.
Source: Massachusetts Institute of Technology
Promising New Target for Parkinson's Disease Therapies
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Science Daily - With a new insight into a model of Parkinson's disease, researchers from the University of Pennsylvania School of Veterinary Medicine have identified a novel target for mitigating some of the disease's toll on the brain.
Narayan G. Avadhani, Harriet Ellison Woodward Professor of Biochemistry and chair of the Department of Animal Biology at Penn Vet, was the senior author on the research. Other department members contributing to the work included Prachi Bajpai, Michelle C. Sangar, Shilpee Singh, Weigang Tang, Seema Bansal and Ji-Kang Fang. Co-authors from Vanderbilt University are Goutam Chowdhury, Qian Cheng, Martha V. Martin and F. Peter Guengerich.
To study Parkinson's, researchers have commonly mimicked the effects of the disease in animals by giving them a compound known as MPTP, a contaminant of the illicit drug MPPP, or synthetic heroin. MPTP causes damage to brain cells that respond to the neurotransmitter dopamine, leading to problems in muscle control, including tremors and difficulty walking.
The common understanding of MPTP's mechanism was that it entered the brain and was eventually converted to the toxic compound MPP+ by the enzyme MAO-B, which is located on the mitochondria of non-dopaminergic (or dopamine-sensitive) neurons. Scientists believed MPP+ was carried by the action of specific transporters into dopaminergic neurons, where it inhibited mitochondrial function and led to cell death.
In the new study, published in the Journal of Biological Chemistry, the Penn-led team turned its attention to yet another molecule, known as mitochondrial CYP2D6, which until recently has been largely uninvestigated. Previous studies in the investigators' laboratory showed that CYP2D6, a protein that is predominantly localized to cells' endoplasmic reticulum, was also targeted to their mitochondria.
Unlike MAO-B, the endoplasmic reticulum-associated CYP2D6 was thought to have a protective effect against MPTP toxicity. The authors now show that mitochondrial CYP2D6 can effectively metabolize MPTP to toxic MPP+, indicating a possible connection between mitochondrial CYP2D6 and Parkinson's.
"About 80 percent of the human population has only one copy of CYP2D6, but the other 20 percent has variant forms of it and some populations have multiple copies," Avadhani said. "In those people, the activity of mitochondrial CYP2D6 can be high, and there have been correlations between these variants and the incidence of Parkinson's disease."
Working with primary neuronal cells in culture, the researchers showed that mitochondrial CYP2D6 could actively oxidize MPTP to MPP+. When they introduced compounds that selectively inhibited the activity of CYP2D6, this conversion process was largely halted. Neuronal degeneration was also greatly reduced.
"If we add MPTP to dopamine-sensitive neurons and also add a CYP2D6 inhibitor, we see marked protection of the neuronal function," Avadhani said. "We believe this is a paradigm shift in how we think about the mechanism of Parkinson's."
A number of MAO-B inhibitors used in the clinical setting for treating Parkinson's disease have unwanted side effects. A mitochondrial CYP2D6 inhibitor represents a much more specific and direct target and may thus cause fewer troublesome side effects.
To take the next step with this finding, Avadhani and his colleagues are developing an animal model and using stem cells to confirm the significance of mitochondrial CYP2D6's role in the development of Parkinson's symptoms.
The study was supported by National Institutes of Health and the Harriet Ellison Woodward Endowment.
Researchers look at melanoma-Parkinson's link
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Bethany Barnes Wick
gvnews.com - Researchers at the University of Arizona are trying to solve a big mystery: Why are Parkinson’s patients more likely to get melanoma — and melanoma patients more likely to get Parkinson’s?
Unraveling the link between diseases “that you think would have nothing to do with each other” could help researchers learn more about Parkinson’s, said Scott Sherman, an associate professor of neurology at the UA.
On the case are scientists from a variety of disciplines who study Parkinson’s and melanoma. Tim Bowden, for example, is a UA professor emeritus of molecular and cellular medicine and a member of the Arizona Cancer Center. He has a long-standing research interest in skin cancer. He’s also a Parkinson’s patient.
Bowden started talking to Sherman, who happens to be his neurologist, and to dermatologist Clara Curiel about a possible connection between the two diseases. Soon, other UA researchers became interested in trying to figure out why the connection exists. Torsten Falk, an assistant professor of neurology, Brian McKay, an associate professor of ophthalmology and vision science, and Lalitha Madhavan, an assistant professor in neurology, brought their expertise to answering the question.
New technology
The research is still in its infancy, Bowden said. The study that is the furthest along involves using technology that recently won the Nobel Prize in Physiology or Medicine by inducing pluripotent stem cells. These cells can make any cell in the body, but they’ve been controversial because in the past the only source was fetal tissue.
Obtaining biopsies from melanoma patients isn’t difficult, but you can’t take brain tissue from living Parkinson’s patients. Using induced pluripotent stem cells provides a workaround to biopsying the brain.
The new technology is “simple and beautiful,” Madhavan said. Researchers create brain tissue by regressing a biopsied skin cell back to the point where it could become any type of cell, making it pluripotent. By applying four different factors in a sequence, researchers can turn the clock back on the cell. From there, they can make the cell become any cell they want. The cell remains specific to the patient who donated the biopsy.
“The fact that (the technology) was given the Nobel award indicates that it is a very important technology,” Madhavan said. “It’s really changing the face of science.”
This technology will allow researchers to study the differences and similarities between skin cells from melanoma patients and the Parkinson’s brain cells made from the induced pluripotent stem cells, Madhavan said.
Researchers just finished collecting skin biopsies from patients with Parkinson’s, patients with melanoma and people without either disease. Both Bowden and his wife had biopsies taken.
The bigger picture
On a practical level, Bowden said, it’s important to get the message out to Parkinson’s patients that they should be screened for melanoma. Although melanoma is preventable, it is crucial to catch it early, as there are very few options once it spreads.
Exploring the unexpected connection between Parkinson’s and melanoma could also give scientists an at-risk population to study. The holy grail in Parkinson’s research is finding a way to slow the loss of brain cells, Sherman said. By the time people are diagnosed with Parkinson’s, however, they have already lost 70 percent of the specialized dopamine neurons in the brain.
Losing these cells hinders patients’ movement. “That’s a tough time for us to try to step in to do damage control because a lot of damage has already been done,” Sherman said.
If researchers could figure out who is at risk and develop tests to diagnose a pre-Parkinson’s condition, they might have a better chance of developing a therapy to protect the brain cells early, Sherman said.
Both Parkinson’s and melanoma have complex causes. The one known connection they share is that the cells affected in both diseases are pigmented.
In the past the presence of neuromelanin, a type of pigment, has been dismissed as an unimportant byproduct. That seemingly small connection is something worth revisiting, Sherman said.
The risk for melanoma may not be as simple as developing a sunburn, Sherman said. There may be complex mechanisms at work that link the two diseases.
Exploring those unexpected connections, he said, might give scientists a better understanding of both diseases.
Russia testing Alzheimer's, Parkinson's medicine
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Margarita Bogatova
The Voice of Russia - Russian scientists have been testing a new medicine that is expected to protect the nervous system and hopefully become a cure for the most wide-spread nervous diseases such as Alzheimer`s and Parkinson`s, as well as strokes and depression.
The medicine is currently undergoing pre-clinical tests. Experts believe that it in the coming years it will give millions of people a hope for recovery.
Treating nervous diseases has always been a challenging and costly task. The treatment for Parkinson`s and Alzheimer`s costs some $1 million with patients required to receive brain injections. Over the past 25 years scientists have been looking for a simpler way of treating these diseases. The most difficult thing about this is a lack of knowledge about chemical processes taking place in the brain, says Larisa Chigaleichik, senior researcher at the Russian Academy of Sciences` Center for Neurology…
"The brain protects itself and does not let medicines in. So we do not only need to know what reactions are taking place there, we have to know how to transfer a medicine directly to the brain cells without harming the liver or kidneys. We are now working to develop new methods of making the medicines more effective. Tests made on animals have proved successful."
The existing medicines are used in brain injections otherwise the human organism, or if to be more exact- the brain’s system of biological protection, would have destroyed them. Proteins that protect neurons from destruction are too big, so making their smaller copies has remained a matter of priority for scientists in the past 25 years. The Russian scientists have demonstrated the best results, says Tatiana Gudasheva, the head of the chemistry department at the Zakusov Scientific Institute…
"Many pharmaceutical companies now produce small molecules that mimic neurotrophins. We have invented the smallest ever molecule that can mimic the neurotrophic effect and can be used in systemic injection."
Systemic injections are alternative schemes of taking medicines – intravenous, intra-abdominal or intramuscular. The institute has been testing the molecule applying to different kind of diseases and deals with patenting the invention.
"We have applied our new method to several scenarios of how Alzheimer`s and Parkinson`s usually develops, we also watched the brain’s reactions caused by a stroke, and each time our tests were successful. We have patented our method in Russia and are going to receive an international patent as well."
The head of the Russian Scientific Institute of Pharmacology Sergei Seredenin has confirmed that after the pre-clinical testing the newly discovered substance could become a real medicine in the near future.
"Although Russian scientists warn against exaggerating the importance of the invention until all tests are over, chances are still quite high for a real breakthrough to take place in treating Alzheimer`s and Parkinson`s."
Genes behind Parkinson’s disease identified
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zeenews.india.com - Washington: Boston University School of Medicine (BUSM) investigators have conducted the first genome-wide evaluation of genetic variants associated with Parkinson’s disease (PD).
The study points to the involvement of specific genes and alterations in their expression as influencing the risk for developing PD.
Jeanne Latourelle, DSc, assistant professor of neurology at BUSM, served as the study’s lead author and Richard H. Myers, PhD, professor of neurology at BUSM, served as the study’s principal investigator and senior author.
A recent paper by the PD Genome Wide Association Study Consortium (PDGC) confirmed that an increased risk for PD was seen in individuals with genetic variants in or near the genes SNCA, MAPT, GAK/DGKQ, HLA and RIT2, but the mechanism behind the increased risk was not determined.
“One possible effect of the variants would be to change the manner in which a gene is expressed in the brains, leading to increased risk of PD,” said Latourelle.
To investigate the theory, the researchers examined the relationship between PD-associated genetic variants and levels of gene expression in brain samples from the frontal cortex of 26 samples with known PD and 24 neurologically healthy control samples.
Gene expression was determined using a microarray that screened effects of genetic variants on the expression of genes located very close to the variant, called cis-effects, and genes that are far from the variant, such as those on a completely different chromosome, called trans-effects.
An analysis of the cis-effects showed that several genetic variants in the MAPT region showed a significant association to the expression of multiple nearby genes, including gene LOC644246, the duplicated genes LRRC37A and LRRC37A2 and the gene DCAKD.
Significant cis-effects were also observed between variants in the HLA region on chromosome 6 and two nearby genes HLA-DQA1 and HLA-DQA1. An examination of trans-effects revealed 23 DNA sequence variations that reached statistical significance involving variants from the SNCA, MAPT and RIT2 genes.
“The identification of the specific altered genes in PD opens opportunities to further study them in model organisms or cell lines with the goal of identifying drugs which may rectify the defects as treatment for PD,” said Myers.
Neurons Made From Adult Cells In The Brain
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medical news today - Finding ways to make new brain cells are important steps in the search for treatments for brain-wasting diseases such as Alzheimer's and Parkinson's. Now a German-led team has discovered how to make new human neurons from another type of adult cell found in the brain.
The researchers write about their work in the 5 October online issue of Cell Stem Cell.
Much of the stem cell research that is going on into making new brain cells focuses on using stem and adult cells from other parts of the body and reprogramming them to form new brain cells and then implanting them into the brain.
For example, earlier this year, Stanford researchers in the US reported how they converted mouse skin cells directly into neural precursor cells, the cells that go on to form the three main types of cell in the brain and nervous system.
But corresponding author of this latest study, Benedikt Berninger, now at the Johannes Gutenberg University Mainz, says they are looking at ways of making new neurons out of cells that are already in the brain.
"The ultimate goal we have in mind is that this may one day enable us to induce such conversion within the brain itself and thus provide a novel strategy for repairing the injured or diseased brain," says Berninger in a press release.
A major challenge of finding cells already in the brain that can be coaxed into forming new neurons, is whether they will respond to reprogramming.
The cells that Berninger and colleagues are focusing on are called pericytes. These cells are found close to blood vessels in the brain and help maintain the blood-brain barrier that stops bacteria and other unwanted material crossing from the bloodstream into the brain.
In other parts of the body, pericytes help with wound healing, which is what drew the team's attention:
"Now, we reason, if we could target these cells and entice them to make nerve cells, we could take advantage of this injury response," says Berninger.
They managed to coax adult human brain pericytes into neuron-like cells with the help of two genes, Sox2 and Mash1:
"Here we show that cells from the adult human cerebral cortex expressing pericyte hallmarks can be reprogrammed into neuronal cells by retrovirus-mediated coexpression of the transcription factors Sox2 and Mash1," write the researchers.
They used a method called "genetic fate mapping" in mice to confirm that the new brain cells had come from pericytes.
When they tested the new cells to see how closely they resembled neurons, they found they could produce electrical pulses and reach out to other neurons, two important features for being able to integrate into neural networks.
There is still a long way to go before what works in the test tube can be made to work in living tissue, but nonetheless, this is an important step in the search for a new way to make brain cells, say the researchers in their conclusions:
"While much needs to be learnt about adapting a direct neuronal reprogramming strategy to meaningful repair in vivo, our data provide strong support for the notion that neuronal reprogramming of cells of pericytic origin within the damaged brain may become a viable approach to replace degenerated neurons."
"Our results raise the possibility of functional conversion of endogenous cells in the adult human brain to induced neuronal fates," they write.