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Procedure Could Help Local Patients Beat Parkinson's Disease

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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.

Acupuncture for Parkinson’s Disease - New Research

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Health cmi.com - New research concludes that acupuncture may be an effective treatment modality for the improvement of symptoms in Parkinson’s Disease patients. Using fMRI imaging, researchers measured the specific effects of needling acupuncture point GB34 (Yanglingquan) on areas of the brain related to Parkinson’s Disease. The researchers discovered that acupuncture activated brain centers that suffer excess deactivation in Parkinson’s Disease patients. Parkinson’s Disease is a degenerative brain disorder. Parkinson’s patients have lower neural responses in brain regions that acupuncture can access and activate. As a result, the researchers conclude that acupuncture at GB34 may improve the symptoms associated with Parkinson’s.

Two groups were compared using functional MRI technology. Group 1 were healthy subjects and group 2 consisted of Parkinson’s patients. The researchers discovered that acupuncture increases neural responses in brain regions associated with Parkinson’s Disease: substantia nigra, caudate, thalamus, putamen. These brain regions are pathologically impaired in Parkinson’s Disease patients but are activated by stimulation of acupuncture point GB34.

The researchers initiated this study citing prior investigations concluding that acupuncture is beneficial to Parkinson’s Disease patients. The researchers note that there is a need for more randomized controlled trials on the subject and conclude that “this study shows that acupuncture may be helpful in the treatment of symptoms involving PD (Parkinson’s Disease).”

Reference:
Yeo, S., Lim, S., Choe, I.-H., Choi, Y.-G., Chung, K.-C., Jahng, G.-H. and Kim, S.-H. (2012), Acupuncture Stimulation on GB34 Activates Neural Responses Associated with Parkinson's Disease. CNS Neuroscience & Therapeutics, 18: 781–790. doi: 10.1111/j.1755-5949.2012.00363.x. Kyung Hee University, Seoul, Korea.

Antioxidant Shows Promise in Parkinson's Disease

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Science Daily - Diapocynin, a synthetic molecule derived from a naturally occurring compound (apocynin), has been found to protect neurobehavioral function in mice with Parkinson's Disease symptoms by preventing deficits in motor coordination.

The findings are published in the May 28, 2013 edition of Neuroscience Letters.

Brian Dranka, PhD, postdoctoral fellow at the Medical College of Wisconsin (MCW), is the first author of the paper. Balaraman Kalyanaraman, PhD, Harry R. & Angeline E. Quadracci Professor in Parkinson's Research, chairman and professor of biophysics, and director of the MCW Free Radical Research Center, is the corresponding author.

In a specific type of transgenic mouse called LRRK2R1441G, the animals lose coordinated movements and develop Parkinson's-type symptoms by ten months of age. In this study, the researchers treated those mice with diapocynin starting at 12 weeks. That treatment prevented the expected deficits in motor coordination.

"These early findings are encouraging, but in this model, we still do not know how this molecule exerts neuroprotective action. Further studies are necessary to discover the exact mode of action of the diaopocynin and other molecules with a similar structure," said Dr. Kalyanaraman.

Clinicians have expressed a need for earlier disease detection in Parkinson's Disease patients; the researchers believe further study of this specific mouse model may allow them to identify new biomarkers that would enable early disease detection, and ultimately allow for better patient care and quality of life.

Scientists identify protein that contributes to symptoms of Parkinson's disease

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Provided by Gladstone Institutes

medicalxpress.com - In a paper being published online today in Neuron, Gladstone Investigator Anatol Kreitzer, PhD, and Talia Lerner, PhD, who worked at Gladstone while completing her graduate studies at the University of California, San Francisco (UCSF), describe how a protein called RGS4 normally helps regulate the activity of neurons in the striatum—the part of the brain that controls movement. But in experimental models of Parkinson's disease, RGS4 does the opposite by actually contributing to problems with motor control. The result is a deterioration of movement and motor coordination, which are the hallmark symptoms of Parkinson's. More than 10 million people suffer from Parkinson's worldwide, including the boxer Muhammad Ali and the actor Michael J. Fox.

Scientists have long known that a drop in dopamine—an important chemical in the brain—is associated with Parkinson's. And for decades patients have taken a drug called Levodopa to boost the brain's dopamine levels. Unfortunately, however, Levodopa's efficacy begins to fade as the disease progresses. So scientists have begun looking for other targets for which they can develop new therapeutic strategies.

"About 60,000 Americans are diagnosed with Parkinson's annually, and dopamine-based therapies often do not provide a long-term solution," said Dr. Kreitzer, who is also an assistant professor of physiology and neurology at UCSF, with which Gladstone is affiliated. "Our discovery that RGS4 may play a role in the development of Parkinson's symptoms, helps us lay the groundwork for a new therapeutic strategy—independent of dopamine."

Drs. Kreitzer and Lerner found that RGS4 is required for dopamine to regulate brain circuits during learning. But when dopamine levels drop dramatically, as in Parkinson's, RGS4 becomes overactive and disrupts these circuits—thereby leading to Parkinson's symptoms. Therefore, they tested whether removing RGS4 could prevent these symptoms.

Drs. Kreitzer and Lerner treated mice lacking RGS4 with a chemical that lowers dopamine levels, mimicking the effects of Parkinson's. They then monitored the mice's motor skills—including their ability to move freely in an open arena and traverse a balance beam—and compared them to Parkinson's mice in which RGS4 remained intact.

As expected, Parkinson's mice with RGS4 intact exhibited major problems with movement. They lacked coordination and often remained frozen in place for long periods of time. When attempting to cross the balance beam, many had repeated slips and falls, while others could not even attempt the task.

But Parkinson's mice without RGS4 performed fluid, coordinated movements with no major problems, even though they also had lower dopamine levels. The vast majority crossed the balance beam without any missteps. Many of the physical traces of Parkinson's had disappeared.

"By discovering how the removal of RGS4 affects brain circuitry at the molecular level, we gained a deeper understanding of the protein's role—both normally and in Parkinson's disease," said Dr. Lerner. "We've also shed light on a previously unknown mechanism by which the dopamine depletion causes the symptoms of Parkinson's disease. We are optimistic that our work could pave the way for a much-needed alternative to Levodopa—such as a drug that has the ability to inactivate RGS4 in Parkinson's patients."

http://medicalxpress.com/news/2012-01-scientists-protein-contributes-symptoms-parkinson.html

Researchers look for clues to progression of Parkinson's disease

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HealthCanal.com - The PPMI study included early, untreated PD patients, and this arm of the study will include pre-symptomatic patients. The study will examine biomarkers indicative of conversion from no motor symptoms to the typical neurological disorder. Patients will undergo Single-Photon Emission Computed Tomography (SPECT) and Magnetic Resonance Imaging (MRI), and have tests to examine brain proteins that mark the disease, and possibly mark the conversion to symptomatic disease.

"Presently, there is no test for diagnosing Parkinson's," says Stewart Factor, DO, professor of neurology at Emory University School of Medicine and principal site investigator of the study. "It is a clinical diagnosis based on history and clinical examination findings.
"Since Parkinson's disease is a progressive disorder, we believe that by learning to recognize pre-motor symptoms for PD, we may be able to develop therapies that would delay or prevent the onset of the impaired movements, tremor and gait problems in PD patients."

In PD, the nerve cells that produce dopamine, a chemical messenger in the brain that is responsible for movement, are degenerating. As time goes on, the dopamine decreases to a threshold level that leads to problems with motor coordination and muscle control. The time from the start of degeneration to the development of symptoms could be as long as 10 years.

The pre-motor arm of PPMI will enroll participants who do not have motor symptoms of Parkinson's disease, but are living with one of three potential risk factors for PD: a reduced sense of smell; rapid eye movement sleep behavior disorder (acting out one's dreams); or a mutation in the LRRK2 gene – the single greatest genetic contributor to PD known to date. Then the participants will be followed over several years to see if, or when, they develop Parkinson's disease.

Volunteers who participate in the Emory trial will complete a brief online survey about their sense of smell. Some of the participants will then be mailed a scratch-and-sniff smell test and brief questionnaire to be completed at home and returned to the researchers.

Once the researchers have collected the information, some individuals may be asked to undergo a SPECT imaging scan to examine the integrity of the dopamine system. If abnormal, they will be asked to participate in the study for the next few years. Alternatively, if they have rapid eye movement sleep behavior disorder, a sleep study will be reviewed and if confirmed they will have the SPECT imaging study done.

"While most people with a reduced sense of smell will not develop PD, the loss or reduction of the ability smell is a common early feature in people with Parkinson's," Factor explains. "Decreased sense of smell is demonstrated in 90 percent of early-stage PD cases. Smell loss begins an average of four years before being diagnosed with the disease."

Factor is director of the Emory Comprehensive Parkinson's Disease Center, and director of the movement disorders program in the Department of Neurology at Emory.

A consortium of 13 industry partners funds the Parkinson's Progression Markers Initiative. Emory is one of 23 official sites involved in the trial.

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.

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

Medical researchers close in on new pathway into brain

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Daniel Chang

The Miami Herald - Stumped for years by a natural filter in the body that allows few substances, including lifesaving drugs, to enter the brain through the bloodstream, physicians who treat neurological diseases may soon have a new pathway to the organ via a technique developed by a physicist and an immunologist working together at Florida International University’s Herbert Wertheim College of Medicine.

The FIU researchers developed the technique to deliver and fully release the anti-HIV drug AZTTP into the brain, but their finding has the potential to also help patients who suffer from neurological diseases such as Alzheimer’s, Parkinson’s and epilepsy, as well as cancer.

“Anything where you have trouble getting drugs to the brain and releasing it, this opens so many opportunities,” said Madhavan Nair, an FIU professor and chair of the medical school’s immunology department.

In an in-vitro laboratory test with HIV-infected cells, Nair and a colleague, Sakhrat Khizroev, a professor of immunology and electrical engineering, attached the antiretroviral drug AZTTP to tiny, magneto-electric nanoparticles. Then, using magnetic energy, they guided the drug across a cell membrane created in the lab to mimic the blood-brain barrier found in the human body.

Once the drug reached its target, researchers triggered its release from the nanoparticle by zapping it with a low-energy electrical current. The drug remained functional and structurally sound after the release, according to the experiment findings.

“We learned to control electrical forces in the brain using magnetics,” said Khizroev, who designed, oversaw and supervised the entire project. “We pretty much opened a pathway to the brain.”

The test findings were published in April in the online peer-reviewed journal Nature Communications. Researchers believe that using this method will allow physicians to send a higher level of AZTTP — up to 97 percent more — to HIV-infected cells in the brain.

Currently, more than 99 percent of the antiretroviral therapies used to treat HIV (human immunodeficiency virus), such as AZTTP, are deposited in the liver, lungs and other organs before they reach the brain.

While anti-viral drugs have helped HIV patients live longer by reducing their viral loads, the drugs cannot pass the blood-brain barrier in significant amounts, which allows the virus to lurk unchecked in the brain and can lead to neurological damage, said Dr. Cheryl Holder, a practicing physician and FIU professor who specializes in treating patients with HIV.

“We know that even though the viral load is undetectable in the blood, we don’t know what’s going on in the brain fully,” Holder said.

HIV causes constant inflammation, she said, and the virus can pool in areas of the brain where medicine cannot reach, potentially causing damage.

“It’s important to get the drug to the brain,” she said, “to help prevent dementia in older patients, and inflammation.”

But the ability to target drug delivery and release it on demand in the brain has been impossible without opening the skull, Nair and Khizroev said.

Nair, an immunologist who specializes in HIV research, and Khizroev, an electrical engineer and physicist, began collaborating on the project about 18 months ago after winning a National Institutes of Health grant to study the use of magnetic particles.

One of the keys to success was controlling the release of the drug without adversely affecting the brain.

The researchers found their solution in the magneto-electric nanoparticles, which are uniquely suited to deliver and release drugs in the brain, Khizroev said. These nanoparticles can convert magnetic energy into the electrical energy needed to release the drugs without creating heat, which could potentially harm the brain.

The development of a new, less-invasive pathway to the brain would open the door to many new medical uses.

Khizroev said he recently returned from a trip to the University of Southern California, where he briefed physicians at the medical school on the technique and its potential for cancer treatment. And Nair said he received a letter recently on behalf of a 91-year-old man suffering from Parkinson’s, asking when the technique might become available for use in people.

That may take a while. With the first phase of testing successfully completed using in-vitro experiments, the second will take place at Emory University in Georgia, where researchers will test the technique on monkeys infected with HIV.

If researchers complete the second phase successfully, clinical trials on humans could follow, Nair said. Approval from the Food and Drug Administration would be required before the technique becomes commercially available, he said.

FIU researchers have applied for a patent and would receive royalties, they said, though the university would benefit the most, in part because a successful research project could open opportunities for more grant funding on other topics.

For Khizroev, who had previously done research on quantum computing and information processing, the project has offered a way to put his scientific knowledge to use in a way that could have a direct affect on people’s health.

“I wanted to apply my knowledge of nanoparticles to something important,” he said.

Breakthrough in Parkinson’s research

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LANA HAIGHT

The Star Phoenix - A Saskatoon doctor is heralding a breakthrough in Parkinson’s disease.

“This opens up the door that I’ve been waiting to open for 30 years,” said Dr. Ali Rajput, neurologist and world expert on Parkinson’s disease.

Rajput and his son Dr. Alex Rajput. who also specializes in Parkinson’s disease, were part of an international research team led by human genetics researchers at the University of British Columbia. The researchers identified an abnormal gene associated with typical late-onset Lewy body Parkinson’s disease. And they are thanking an extended family from Saskatchewan for playing a significant role.

Twelve of the 57 members of the family who participated in the study had been diagnosed with Parkinson’s disease. Rajput examined the first family member with Parkinson’s in 1983. During the years, others came to be diagnosed with the disease. As some of the family members died, their brains were donated to Rajput’s collection of more than 500 brains. The family wants to remain anonymous.

“A breakthrough like this would not be possible without their involvement and support. They gave up considerable time, contributed clinical information, donated blood samples, participated in PET imaging studies and — on more than one occasion following the death of a family member — donated brain samples,” says Matthew Ferrer, the UBC medical genetics professor who led the study, in news release issued by the University of Saskatchewan and UBC.

“We are forever indebted to their generosity and contribution to better understanding — and ultimately finding a cure — for this debilitating disease.”

The prevalence of Parkinson’s in Saskatchewan is about 350 people for every 100,000 population, similar rest of the world. Symptoms of the progressive condition include tremors, slowness and stiffness, imbalance and rigidity of muscles. The condition is caused when dopamine, the chemical in the brain that carries signals between nerves, is not being produced.

The latest research determined that the abnormal gene called DNAJC13 causes dopamine-producing cells to die.

While the discovery is considered a major breakthrough, Rajput says much more work needs to be done to find ways to detect Parkinson’s at its early stages and to develop drugs that will stop the progression of the disease. He’s hoping some of that work will continue to be done in Saskatchewan, but that will require more neurologists to take an interest in the research. He also would like to see more people agreeing to donate organs, including their brains, for research after they die.

Parkinson’s: Stem Cell-Derived Neurons Renew Cognitive Function: Study

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guardianlv.com - Sanford-Burnham researchers convince transplanted stem cell-derived neurons to direct cognitive function—getting us a step closer to using these cells to treat Parkinson’s disease, Alzheimer’s disease and other neurodegenerative conditions.

Researchers and patients look forward to the day when stem cells might be used to replace dying brain cells in Alzheimer’s disease and other neurodegenerative conditions. Scientists are currently able to make neurons and other brain cells from stem cells, but getting these neurons to properly function when transplanted to the host has proven to be more difficult. Now, researchers at Sanford-Burnham Medical Research Institute have found a way to stimulate stem cell-derived neurons to direct cognitive function after transplantation to an existing neural network. The study was published in the Journal of Neuroscience.

“We showed for the first time that embryonic stem cells that we’ve programmed to become neurons can integrate into existing brain circuits and fire patterns of electrical activity that are critical for consciousness and neural network activity,” said Stuart A. Lipton, M.D., Ph.D., senior author of the study. Lipton is director of Sanford-Burnham’s Del E. Webb Neuroscience, Aging, and Stem Cell Research Center and a clinical neurologist.

The trick turned out to be light. Lipton and his team—including Juan Piña-Crespo, Ph.D., D.V.M., Maria Talantova, M.D., Ph.D., and other colleagues at Sanford-Burnham and Stanford University—transplanted human stem cell-derived neurons into a rodent hippocampus, the brain’s information-processing center. Then they specifically activated the transplanted neurons with optogenetic stimulation, a relatively new technique that combines light and genetics to precisely control cellular behavior in living tissues or animals.

To determine if the newly transplanted, light-stimulated human neurons were actually working, Lipton and his team measured high-frequency oscillations in existing neurons at a distance from the transplanted ones. They found that the transplanted neurons triggered the existing neurons to fire high-frequency oscillations. Faster neuronal oscillations are usually better—they’re associated with enhanced performance in sensory-motor and cognitive tasks.

To sum it up, the transplanted human neurons not only conducted electrical impulses, they also roused neighboring neuronal networks into firing—at roughly the same rate they would in a normal, functioning hippocampus.

The therapeutic outlook for this technology looks promising. “Based on these results, we might be able to restore brain activity—and thus restore motor and cognitive function—by transplanting easily manipulated neuronal cells derived from embryonic stem cells,” Lipton said.

The research for this study was funded by the California Institute for Regenerative Medicine (Comprehensive Grant RC1-00125-1) and the U.S. National Institutes of Health (Eunice Kennedy Shriver National Institute of Child Health & Human Development grant P01 HD29587; National Institute of Environmental Health Sciences grant P01 ES016738; National Institute of Neurological Disorders and Stroke grant P30 NS076411; National Eye Institute grants R01 EY05477, and R01 EY09024).

Study Authors are; Piña-Crespo JC, Talantova M, Cho EG, Soussou W, Dolatabadi N, Ryan SD, Ambasudhan R, McKercher S, Deisseroth K, & Lipton SA (2012). High-Frequency Hippocampal Oscillations Activated by Optogenetic Stimulation of Transplanted Human ESC-Derived Neurons. The Journal of Neuroscience, 32 (45), 15837-42 PMID: 23136422

Guest Author Dr. Heather Buschman, Ph.D., is the Scientific Communications Manager at Sanford-Burnham Medical Research Institute in La Jolla, Calif., where she writes about research news in cancer, stem cells, diabetes, obesity and more.

Jim Donahue

Stem cell transplant boosts function slightly in Parkinson's monkeys

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Eryn Brown

Los Angeles Times - In a small but hopeful step for researchers working on therapies to treat Parkinson’s disease, a team in Japan has used stem cells harvested from bone marrow to restore function in monkeys with the debilitating condition.

The cell transplants didn’t cure the macaques, but did improve motor skills in the animals and appeared to do so safely, the scientists wrote Monday in the Journal of Clinical Investigation — suggesting that stem cells from bone marrow might someday be a useful source for treatments of Parkinson’s in humans.

“To the best of our knowledge, this study is the first to show restoration of dopaminergic function and motor behaviors in parkinsonian primate animals” after treatment with stem cell-derived neurons, they wrote.

Stem cells are early-stage precursor cells that develop into the mature cells in the body. Scientists have long hoped to learn how to use them to replace cells and tissues damaged by accident or disease.

Parkinson’s has seemed like a good candidate for stem cell-derived therapies because people with the disorder have lost cells in the brain, or neurons, that produce the neurotransmitter dopamine. (For more about Parkinson’s read this page from the NIH’s National Institute of Neurological Disorders and Stroke.) If stem cells could be coaxed to develop into healthy, functioning dopaminergic neurons and then introduced into the brain, the thinking goes, perhaps patients could get relief from tremors, loss of balance and other debilitating Parkinson’s symptoms.

The Japanese team, led by Takuya Hayashi of the RIKEN Center for Molecular Imaging Science in Kobe, Japan, conducted its research on a group of 10 adult macaque monkeys. They induced Parkinson’s disease on the left side of the animals’ bodies.

They removed bone marrow from the hip bonesof the macaques, isolating so-called mesenchymal stem cells — the same type of cells that are sometimes harvested to treat patients with leukemia. (While mesenchymal stem cells can differentiate to become a variety of different types of cells including bone, cartilage and fat, they are not the same as embryonic stem cells or induced pluripotent stem cells, which can develop into any type of cell in the body.) The team used a previously reported method to turn the mesenchymal stem cells into dopamine-producing neurons.

Hayashi and his colleagues studied the neurons they created in the lab to assure that they were indeed dopamine-producing, and then administered treated cells to five of the monkeys. Each of the five monkeys received cells derived from his own bone marrow. The remaining monkeys received sham treatments.

Animals who received the cell treatments had improved motor function, the team reported. What’s more, through the use of PET scans and postmortem tissue analysis, the researchers determined that the implanted neurons continued producing small amounts of dopamine for at least nine months. The monkeys did not develop tumors, always a concern with stem-cell based therapies. Because the cells came from the monkeys’ own bone marrow, tissue rejection wasn’t an issue either. And the stem cells' origin in mature animals — not fetuses — sidestepped availability issues and ethical considerations involved in using fetal tissue, the scientists wrote.

Before the treatment might be considered appropriate for humans, they said, further studies will be needed to improve the viability of the cells once implanted, and to boost their therapeutic effect. But, they added, the approach “may expand the availability of cell sources for cell-based therapies for patients with Parkinson’s disease.”

Scripps Florida Scientists Design a Potential Drug Compound that Attacks Parkinson’s Disease on Two Fronts

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HealthCanal.com - In a new study published recently online ahead of print by the journal ACS Chemical Biology, the scientists describe a “dual inhibitor”—two compounds in a single molecule—that attacks a pair of proteins closely associated with development of Parkinson’s disease.

“In general, these two enzymes amplify the effect of each other,” said team leader Phil LoGrasso, a TSRI professor who has been a pioneer in the development of JNK inhibitors for the treatment of neurodegenerative diseases. “What we were looking for is a high-affinity, high-selectivity treatment that is additive or synergistic in its effect—a one-two punch.”

That could be what they found.

This new dual inhibitor attacks two enzymes—the leucine-rich repeat kinase 2 (LRRK2) and the c-jun-N-terminal kinase (JNK)—pronounced “junk.” Genetic testing of several thousand Parkinson’s patients has shown that mutations in the LRRK2 gene increase the risk of Parkinson’s disease, while JNK has been shown to play an important role in neuron (nerve cell) survival in a range of neurodegenerative diseases. As such, they have become highly viable targets for drugs to treat disorders such as Parkinson’s disease.

A dual inhibitor ultimately would be preferred over separate individual JNK and LRRK2 inhibitors because a combination molecule would eliminate complications of drug-drug interactions and the need to optimize individual inhibitor doses for efficacy, the study noted.

Now the team’s new dual inhibitor will need to be optimized for potency, high selectivity (which reduces off-target side effects) and bioavailability so it can be tested in animal models of Parkinson’s disease.

The first author of the study, “A Small Molecule Bidentate-Binding Dual Inhibitor Probe of the LRRK2 and JNK Kinases,” is Yangbo Feng of TSRI. Other authors include Jeremy W. Chambers, Sarah Iqbal,Marcel Koenig, HaJeung Park, Lisa Cherry, Pamela Hernandez and Mariana Figuera-Losada. For more information see http://pubs.acs.org/doi/abs/10.1021/cb3006165

The study was supported by the National Institutes of Health grant NS057153.

Scientists Identify 'Clean-Up' Snafu That Kills Brain Cells in Parkinson's Disease

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sciencedaily.com - Researchers at Albert Einstein College of Medicine of Yeshiva University have discovered how the most common genetic mutations in familial Parkinson's disease damage brain cells. The study, which published online today in the journal Nature Neuroscience, could also open up treatment possibilities for both familial Parkinson's and the more common form of Parkinson's that is not inherited.

Parkinson's disease is a gradually progressing disorder of the nervous system that causes stiffness or slowing of movement. According to the Parkinson's Disease Foundation, as many as one million Americans are living with the disease.

The most common mutations responsible for the familial form of Parkinson's disease affect a gene called leucine-rich repeat kinase-2 (LRRK2). The mutations cause the LRRK2 gene to code for abnormal versions of the LRRK2 protein. But it hasn't been clear how LRRK2 mutations lead to the defining microscopic sign of Parkinson's: the formation of abnormal protein aggregates inside dopamine-producing nerve cells of the brain.

"Our study found that abnormal forms of LRRK2 protein disrupt an important garbage-disposal process in cells that normally digests and recycles unwanted proteins including one called alpha-synuclein -- the main component of those protein aggregates that gunk up nerve cells in Parkinson's patients," said study leader Ana Maria Cuervo, M.D., Ph.D., professor of developmental and molecular biology, of anatomy and structural biology, and of medicine and the Robert and Renee Belfer Chair for the Study of Neurodegenerative Diseases at Einstein.

The name for the disrupted disposal process is chaperone-mediated autophagy (the word "autophagy" literally means "self-eating"). It involves specialized molecules that "guide" old and damaged proteins to enzyme-filled structures called lysosomes; there the proteins are digested into amino acids, which are then recycled within the cell.

"We showed that when LRRK2 inhibits chaperone-mediated autophagy, alpha-synuclein doesn't get broken down and instead accumulates to toxic levels in nerve cells," said Dr. Cuervo.

The study involved mouse neurons in tissue culture from four different animal models, neurons from the brains of patients with Parkinson's with LRRK2 mutations, and neurons derived from the skin cells of Parkinson's patients via induced pluripotent stem (iPS) cell technology. All the lines of research confirmed the researchers' discovery.

"We're now looking at ways to enhance the activity of this recycling system to see if we can prevent or delay neuronal death and disease," said Dr. Cuervo. "We've started to analyze some chemical compounds that look very promising."

Dr. Cuervo hopes that such treatments could help patients with familial as well as nonfamilial Parkinson's -- the predominant form of the disease that also involves the buildup of alpha-synuclein.

Dr. Cuervo is credited with discovering chaperone-mediated autophagy. She has published extensively on autophagy and its role in numerous diseases, such as Huntington's disease, and its role in age-related conditions, including organ decline and weakened immunity. Dr. Cuervo is co-director of Einstein's Institute of Aging Research.

The paper is titled "Interplay of LRRK2 with chaperone-mediated autophagy." In addition to Dr. Cuervo, other Einstein contributors include Samantha J. Orenstein, a graduate student who performed most of this study as part of her Ph.D. thesis; Inmaculada Tasset, Ph.D.; Esperanza Arias, Ph.D.; and Hiroshi Koga, Ph.D., all members of Dr. Cuervo's group. Additional co-authors are: Sheng-Hang Kuo Ph.D., David Sulzer Ph.D., Etty Cortes, M.D., and Lawrence S. Honig, M.D. (Columbia University, NY); William Dauer, M.D., (University of Michigan, Ann Arbor, MI); Irene Fernandez-Carasa and Antonella Consiglio, Ph.D., (University of Barcelona, Barcelona Spain); and Angel Raya, M.D., Ph.D., (Institucio Catalana de Recerca I Estudies Avancas, Barcelona, Spain).

This work was supported by grants from the National Institute on Aging (AG031782 and AG08702), the National Institute of Neurological Disorders and Stroke Udall Center of Excellence both part of the National Institutes of Health; The Rainwaters Foundation, The Beatrice and Roy Backus Foundation, JPB Foundation; Parkinson's Disease Foundation; Fondazione Guido Berlucchi; Centers for Networked Biomedical Research; Ministry of Economy and Competitiveness; a Hirschl/Weill-Caulier Career Scientist Award; and a gift from Robert and Renee Belfer.

Scientists Identify Brain Circuitry Associated with Addictive, Depressive Behaviours

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Discovery Has Implications for Neurodegenerative and Psychiatric Disorders
Anne Holden

UCSF.edu/news - cientists at the UCSF-affiliated Gladstone Institutes have determined how specific circuitry in the brain controls not only body movement, but also motivation and learning, providing new insight into neurodegenerative disorders such as Parkinson’s disease — and psychiatric disorders such as addiction and depression.

Previously, researchers in the laboratory of Gladstone Investigator Anatol Kreitzer, PhD, discovered how an imbalance in the activity of a specific category of brain cells is linked to Parkinson’s.

Now, in a paper published online today in Nature Neuroscience, Kreitzer, who is also an assistant professor of physiology at UCSF, and his team used animal models to demonstrate that this imbalance may also contribute to psychiatric disorders. These findings also help explain the wide range of Parkinson’s symptoms — and mark an important step in finding new treatments for those who suffer from addiction or depression.

“The physical symptoms that affect people with Parkinson’s —including tremors and rigidity of movement — are caused by an imbalance between two types of medium spiny neurons in the brain,” said Kreitzer, whose lab studies how Parkinson’s disease affects brain functions. “In this paper we showed that psychiatric disorders — specifically addiction and depression —might be caused by this same neural imbalance.”

Normally, two types of medium spiny neurons, or MSNs, coordinate body movements. One type, called direct pathway MSNs (dMSNs), acts like a gas pedal. The other type, known as indirect pathway MSNs (iMSNs), acts as a brake. And while researchers have long known about the link between a chemical in the brain called dopamine and Parkinson’s, Gladstone researchers recently clarified that dopamine maintains the balance between these two MSN types.

But abnormal dopamine levels are implicated not only in Parkinson’s, but also in addiction and depression. Kreitzer and his team hypothesized that the same circuitry that controlled movement might also control the process of learning to repeat pleasurable experiences and avoid unpleasant ones—and that an imbalance in this process could lead to addictive or depressive behaviors.

Kreitzer and his team genetically modified two sets of mice so that they could control which specific type of MSN was activated. They placed mice one at a time in a box with two triggers — one that delivered a laser pulse to stimulate the neurons and one that did nothing. They then monitored which trigger each mouse preferred.

“The mice that had only dMSNs activated gravitated toward the laser trigger, pushing it again and again to get the stimulation — reminiscent of addictive behavior,” said Alexxai Kravitz, PhD, Gladstone postdoctoral fellow and a lead author of the paper. “But the mice that had only iMSNs activated did the opposite. Unlike their dMSN counterparts, the iMSN mice avoided the laser stimulation, which suggests that they found it unpleasant.” These findings reveal a precise relationship between the two MSN types and how behaviors are learned. They also show how an MSN imbalance can throw normal learning processes out of whack, potentially leading to addictive or depressive behavior.

“People with Parkinson’s disease often show signs of depression before the onset of significant movement problems, so it’s likely that the neural imbalance in Parkinson’s is also responsible for some behavioral changes associated with the disease,” said Kreitzer, who is also an assistant professor of physiology at UCSF.. “Future research could discover how MSNs are activated in those suffering from addiction or depression—and whether tweaking them could reduce their symptoms and improve their quality of life.

Graduate student Lynne Tye was also a lead author on this paper. Funding came from a variety of sources, including the W.M. Keck Foundation, the Pew Biomedical Scholars Program, the McKnight Foundation and the National Institutes of Health.

Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases.

UCSF is a leading university dedicated to promoting health worldwide through advanced biomedical research, graduate-level education in the life sciences and health professions, and excellence in patient care.

http://www.ucsf.edu/news/2012/04/11959/scientists-identify-brain-circuitry-associated-addictive-depressive-behaviors

Researchers Discover Key Protein In Development Of Parkinson’s Disease

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Brett Smith

redorbit.com - By working with mouse and fruit fly hearts, researchers at Washington University (WUSTL) School of Medicine, St. Louis identified a key protein that has a connection with Parkinson’s disease and heart failure.

According to a new report in the journal Science, a protein known as mitofusin 2 (Mfn2) is the missing link in the chain-reaction that starts with mitochondrial dysfunction and ends with Parkinson’s disease or heart failure, depending on the affected organ.

“If you have Parkinson’s disease, you have a more than two-fold increased risk of developing heart failure and a 50 percent higher risk of dying from heart failure,” senior author Dr. Gerald W. Dorn II, MD, a professor of Medicine at WUSTL, said in a statement. “This suggested they are somehow related, and now we have identified a fundamental mechanism that links the two.”

Mitochondria are known as the power plant of the cell and heart cells rely on large numbers on mitochondria to keep functioning. If cells allow poorly functioning mitochondria to build up, the results can be catastrophic. Healthy cells typically identify bad mitochondria and remove them.

Researchers have been working since 2006 to identify the mysterious middle section of the chain that causes the disruption of sick mitochondria’s ability to communicate to the rest of the cell it needs to be destroyed.

“This was a big question,” Dorn said. “Scientists would draw the middle part of the chain as a black box. How do these self-destruct signals inside the mitochondria communicate with proteins far away in the surrounding cell that orchestrate the actual destruction?

“To my knowledge, no one has connected an Mfn2 mutation to Parkinson’s disease,” he added. “And until recently, I don’t think anybody would have looked. This isn’t what Mfn2 is supposed to do.”

Normally, mitochondria import and then destroy a molecule called PINK. When mitochondria aren’t functioning properly, they can’t destroy PINK and its levels begin to rise.

The WUSTL researchers found once PINK concentration reaches a certain level, the molecule makes a chemical change to Mfn2, which is located on the surface of mitochondria. The altered Mfn2 then binds the mitochondria to a molecule called Parkin within the surrounding cell. After binding to Mfn2, Parkin labels the sick mitochondria for destruction by the cell.

“But if you have a mutation in PINK, you get Parkinson’s disease,” Dorn said. “About 10 percent of Parkinson’s disease is attributed to these or other mutations that have been identified.”

According to the researchers, their discovery could help improve the diagnosis for both Parkinson’s disease and heart failure.

“I think researchers will look closely at inherited Parkinson’s cases that are not explained by known mutations,” Dorn explained. “They will look for loss of function mutations in Mfn2, and I think they are likely to find some.”

The cardiologist said his medical team has already detected mutations in Mfn2 that could explain certain familial forms of heart failure.

“In this case, the heart has informed us about Parkinson’s disease, but we may have also described a Parkinson’s disease analogy in the heart,” he said. “This entire process of mitochondrial quality control is a relatively small field for heart specialists, but interest is growing.”

Rare Glimpse Into Parkinson’s Disease Using Neuroimaging Technology

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Staff Editor

HealthNewsDigest.com - A University of Nebraska Medical Center research team has found a way to monitor brain injuries that occur in Parkinson's disease providing clinicians a rare glimpse into the disease process.

By using magnetoencephalography (MEG) imaging Tony Wilson, Ph.D., an assistant professor in the UNMC Department of Pharmacology and Experimental Neuroscience and lead study investigator, was able to pinpoint the regions of the brain affected by this debilitating disease.

The results of Dr. Wilson's research were published in the Journal Cerebral Cortex, one of the top ranked neuroscience journals.

In the year-long study, Dr. Wilson and colleagues scanned the brains of 19 patients with Parkinson's and 16 without to see how different regions of the brain were involved in the initiation of basic movements.

Using MEG imaging, the investigative team identified the regions of the brain that became engaged when the person performed a simple hand movement.

"The scans revealed that patients with Parkinson's disease had clear deficits in critical brain centers during the movements," Dr. Wilson said.

Now that the specific regions of the brain affected by Parkinson's have been identified, the next step is to develop medications designed to slow the disease's progression.

"Up to this point, we have not had a foolproof way of diagnosing or monitoring Parkinson's. The hope is that this will become a biomarker that will aid clinicians in determining the best therapeutic methods to use for their patients," he said.

"This research provides an exciting new avenue for translational research," said Howard Gendelman, M.D., chairman of the UNMC Department of Pharmacology and Experimental Neuroscience and co-investigator on the study.

Gendelman and his team have, for more than 12 years, worked to not only understand Parkinson's disease progression but also to slow it through immune therapy. The work would not have been possible without a vigorous collaboration between neurologists, statisticians, psychologists and neuroscientists.

"Nebraska is perhaps one of the few research centers worldwide that boasts of so many people with divergent interests able to work together so effectively," Dr. Gendelman said.

He said this new technique will aid his research team's work into a novel therapy that has been proven in mouse models to reverse the neurodegenerative effects of the disease by changing the body's immune response.

"The technique offers opportunities to accurately diagnose the disease and gauge its progression in ways that are not possible with the standard neurological exam performed in the clinic," he said.

No other test provides that kind of accuracy with the relative ease and safety that this one does, said R. Lee Mosley, Ph.D., a study collaborator and associate professor in the PEN department adding that UNMC is one of a few places in the United States that has a MEG system.

Parkinson's disease is caused by the loss of neurons that produce dopamine, a nerve signaling chemical that controls movement and balance. Dr. Gendelman said the diagnosis and treatment of Parkinson's disease is of critical importance, not just nationwide, but in Nebraska where the incidence is so high.

The Parkinson's Disease Foundation estimates that about 1 million people in the United States and more than 4 million people worldwide have the disease. The incidence rate of Parkinson's disease is higher in Nebraska than in any other state in the country.

"Dr. Wilson has become an indispensible part of the research team providing new and important ways to better diagnosis this disease in a way that ensures patients are not harmed in any way, while still showing that they are responding appropriately to therapy," Dr. Gendelman said.

The participating authors of this study included: Elizabeth Heinrichs-Graham, a Ph.D. trainee and student inthe neuroscience and behavior program at the University of Nebraska at Omaha; UNMC neurologists, Pamela Santamaria, M.D., and Diego Torres-Russotto, M.D.; and UNMC statistician Jane Meza, Ph.D.

Peptides helping researchers in search for Parkinson's disease treatment

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Australian researchers have taken the first step in using bioactive peptides as the building blocks to help 'build a new brain' to treat degenerative brain disease.

medicalxpress.com - Deakin University biomedical scientist Dr Richard Williams is working in a team with Dr David Nisbet from the Australian National University and Dr Clare Parish at the Florey Neuroscience Institute to develop a way to repair the damaged parts of the brain that cause Parkinson's disease.

Parkinson's disease develops when the brain cells (or neurons) that produce the chemical dopamine die or are damaged. Dopamine neurons produce a lubricant that helps the brain transmit signals to the body that control muscles and movement. When these cells die or are damaged the result is the shaking and muscle stiffness that are among the common symptoms of the disease.

"We are looking at a way of helping the brain to regenerate the dead or damaged cells that transport dopamine throughout the body," Dr Williams said.

"Peptides help the body heal itself, providing many positive benefits for health, particularly in regenerative medicine; this is why the sports people were using them to recover more quickly in the current doping scandal."

Peptides are both the building blocks and the messengers of the body; the team has used them to mimic the normal brain environment and provide the chemical signals needed to help the brain function.

"Peptides stick together like Lego blocks, so in the first stage of the project we have been able to make a three dimensional material or tissue scaffold that provides the networks cells need to grow; but the peptides also carry instructions in the form of chemical signals which tell the cells to grow into new neurons," Dr Williams explained.

"Importantly, this material has the same consistency as the brain, does not cause chronic inflammation and is non-toxic to the body.

"Our aim is to use this scaffold material to support the patient's own stem cells that could be turned into dopamine neurons and implanted back into the brain. We expect that when implanted the material and stem cells would be accepted by the brain as normal tissue and grow to replace the damaged or dead cells."

While the research is not yet complete, Dr Williams is excited by the possibilities this work offers to the treatment of degenerative conditions.

"It is no secret that we are living longer, and with this we are seeing an increase in many conditions that come about because of ageing such Parkinson's. By developing biomaterials, like the ones we are working on, it could be possible to help the body to regenerate and provide an improved quality of life to the older members of our community," he said.

"This work can also be adapted to other parts of the body which struggle to repair themselves, such as new cartilage for joints, muscle and heart cells, bones and teeth. Ultimately, it will be like taking your car to the garage to have new parts fitted to replace the worn out ones."

The results of the first stage of this Australian Research Council funded project will be published in the international journal Soft Matter.

Parkinson's-related mutations may also affect vision

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News Medical - The most common genetic cause of Parkinson's is not only responsible for the condition's distinctive movement problems but may also affect vision, according to new research by scientists at the University of York.

Parkinson's, the second most common form of neurodegenerative disease, principally affects people aged over 60. Its most common symptom is tremor and slowness of movement (bradykinesia) but some people with Parkinson's also experience changes in vision.

Now for the first time, researchers in the University's Department of Biology have established a link between a mutation which triggers Parkinson's and problems with vision in an animal model.

The latest research, part-funded by leading research charity Parkinson's UK is published in Human Molecular Genetics. Scientists at York studied the impact of the most common Parkinson's-related mutation on nerve cells in the visual system of the fruit fly, Drosophila.

Using electroretinagram (ERG) technology they found a gradual loss of function in eye nerve cells with the mutant gene. The fly visual system is a useful laboratory model as it contains similar amounts of dopamine to the human eye.

However, the research team, which was supported by the University's Centre for Chronic Disease and Disorders (C2D2), found that other Parkinson's-related mutations did not affect eye nerve cell function and there was no loss of vision.

Dr Chris Elliott, who led the research, said: "This is a significant step forward as it will help to identify those people with Parkinson's who may be at greater risk of changes in their vision. It will assist clinicians to manage the condition more effectively.

"We have to get away from the idea that Parkinson's is only about movement problems. This work indicates that changes in vision may also affect people with the most common form of inherited Parkinson's."

Claire Bale, Research Communications Manager at Parkinson's UK added: "This new research has uncovered a potentially interesting relationship between one of the most common genes linked to Parkinson's and the development of visual problems.

"But crucially this study looked at fruit flies, so we need to do more research to find out how relevant the findings are to people living with the condition.

"If you have Parkinson's and notice changes in your eyesight, such as blurred or double vision, it's important to discuss this with your specialist or Parkinson's nurse."

Source: University of York

Parkinson's disease protein found in intestinal wall

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Denise Dador

abclocal.go.com - Usually scientists look at the brain when it comes to researching Parkinson's disease. But a recent study turned up a surprising clue in the intestines. This unexpected finding may change how the devastating disease is treated.

Researchers at Rush University Medical Center have discovered a bad protein in the intestines that only shows up in Parkinson's patients.

"This is a cell, a living cell, that's got the protein accumulated in there," said Doctor Kathleen Shannon.

Shannon says when the protein gets to the brain, Parkinson's symptoms appear.

"If you could detect it when it's just in the intestinal wall and then prevent the spread, then patients would never have to develop the typical nervous system symptoms that cause so much disability," said Shannon.

Doctor Jeffrey Kordower, a neurology researcher at Rush University Medical Center, hopes the protein turns out to be a biomarker.

"Maybe we'll be able to tell who gets Parkinson's disease before they get Parkinson's," said Kordower.

The goal is to develop a screening process and a treatment that attacks the protein while it's still in the intestines.

Researchers say there's no known cure for Parkinson's disease and this treatment is aimed at controlling the symptoms of the disease before they progress.

Parkinson’s Disease Cure May Lie in Unravelling Secrets of the Brain

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Virtual Brain to allow scientists to decode mysteries of the complex organ
Perviz Walji

The Guardian Express (UK) - Cures for Parkinson’s disease and other ailments such as Alzheimer’s disease, depression, and epilepsy may lie in unraveling the secrets of the brain, according to scientists.

Scientists have created a 3-D replica of the human brain that will allow them to unlock its secrets and decode its mysteries in their next frontier in brain exploration.

Hailed as a “technological tour de force,” the virtual brain, known as Bigbrain atlas, is intended to allow the scientists to better understand the structure of the brain and also the most miniscule details of its cell networks.

According to scientists, there are close to a 100 billon neurons all connected in a complex network in the human brain.

Christof Koch, Chief Scientific Officer at the Allen Institute for Brain Science, recently compared the human brain to the Amazon rainforest, in an NPR interview on “Science Friday.” According to him there are as many neurons in the brain as there are trees in the forest. Like the trees and vines in the rainforest, the brain’s neurons are also tangled up in a complex network.

“There are an enormous number of neurons in the brain,” Dr. Koch said. “Just like in the rainforest, there is enormous diversity of them, and that’s the complexity we are facing.”

Comparing the study of the brain to astrophysics, Dr. Koch said, “we are facing just like in astrophysics over the last 100 years, every new, each new generation of astronomers and astrophysicists discovers that the universe is yet bigger, yet bigger than we thought.

Each time we look with better and better tools, with better microscopes, we see more and more complexity. So now we realize there are not just two types of nerve cells, but there are probably a 1000 different types of nerve cells, just like there are 1000 different species of trees in the rain forest.”

The 3-D replica is intended to help researchers learn how minute building blocks work together to make us who and what we are.

Researchers say the information gained from the study of this virtual brain has far larger implications in the study of diseases. By unravelling the secrets of the brain, scientists will more accurately determine brain tissues that are linked to ailments such as Alzheimer’s disease, Parkinson’s disease, depression, and epilepsy. In this exciting new future, scientist may be able to remove tumours from brain with little damage the organ itself.

Elaborating on this theory, Dr. Koch said, “And we know from certain mental diseases, you know, I mentioned schizophrenia, there’s also Alzheimer’s and Parkinson’s, it all involves, various complicated mis-wiring. And so in order to help people ultimately, we need to understand the wiring and mis-wiring, and that can primarily be done at the level of individual cells.”

The virtual BigBrain atlas was created with a real human brain that belonged to a 65-year-old European woman who had willed her remains for biomedical research. According to researchers, it was carved into 7,404 vertical slices and preserved on slides. Researchers said looking at samples under a microscope can provide a high level of detail. A five year effort went into this project.

“It absolutely will help us build bridges between the brain’s structure and its function,” Dr. John Mazziotta, a UCLA neuroscientist said. “The more we understand the components of the machinery, the better position we’re in to understand how it works. It’s pretty hard to understand how a complex electronic device works if you don’t have a good wiring diagram.”

According to reports, BigBrain uncovers the brain’s structures with a resolution that is 50 times stronger than the brain maps produced by medical imaging techniques such as the MRI scanners. With so much detail revealed, it will allow researchers, physicians and drug developers to examine the brain in a way that neither MRIs nor tissue samples on microscope slides can provide.

“People are pretty excited about it,” Dr. Mazziotta said at a recent meeting of the “Organization for Human Brain Mapping” in Seattle, where BigBrain was presented to scientists. A cure for Parkinson’s and other brain conditions may rely on this research.