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Welcome to Our Parkinson's Place


I copy news articles pertaining to research, news and information for Parkinson's disease, Dementia, the Brain, Depression and Parkinson's with Dystonia. I also post about Fundraising for Parkinson's disease and events. I try to be up-to-date as possible. I have Parkinson's
diseases as well and thought it would be nice to have a place where
updated news is in one place. That is why I began this blog.
I am not responsible for it's contents, I am just a copier of information searched on the computer. Please understand the copies are just that, copies and at times, I am unable to enlarge the wording or keep it uniformed as I wish. This is for you to read and to always keep an open mind.
Please discuss this with your doctor, should you have any questions, or concerns. Never do anything without talking to your doctor. I do not make any money from this website. I volunteer my time to help all of us to be informed. Please no advertisers. This is a free site for all.
Thank you.


Saturday, February 7, 2015

UCB announces positive top-line results from two phase 3 studies of Neupro to treat Parkinson’s disease


Brussels, Belgium

Saturday, February 07, 2015, 10:00 Hrs  [IST]
UCB announced positive top-line results from two phase 3 studies evaluating Neupro (rotigotine transdermal patch) in the treatment of patients in China with early- and advanced-stage idiopathic Parkinson’s disease.

Results from the phase 3 study in patients with early-stage Parkinson’s disease demonstrated that rotigotine transdermal patch significantly improved symptoms when compared to placebo. In addition, data from the phase 3 study in advanced Parkinson’s disease showed that patients treated with rotigotine had a significantly greater decrease in their ‘off’ time, or periods of poor mobility, slowness and stiffness, compared to those patients taking placebo. The adverse event profile observed in these studies and in this Chinese population were consistent with that known for rotigotine.

Based on the positive results UCB intends to submit a regulatory application in China in 2015 for Neupro in the treatment of early- and advanced-stage Parkinson’s disease.

“Parkinson’s disease is a chronic and progressive neurological disease that can significantly impact patients’ lives. The positive results from the two Phase 3 studies in China evaluating Neupro in Parkinson’s disease is a significant milestone to making Neupro available to more patients and healthcare professionals worldwide. Subject to regulatory approval, we hope to deliver Neupro in China as a new treatment option to patients with early- and advanced-stage Parkinson’s disease,” says Professor Dr. Iris Loew-Friedrich, chief medical officer and executive vice president, UCB.

One of the two phase 3 studies was a  multicentre, randomised, double-blind, parallel-group, placebo-controlled, 24-week study that evaluated the efficacy and safety of rotigotine (escalating weekly dose starting with daily doses of 2 mg/24 hours to 8 mg/24 hours) in 247 adult patients (30 years and older) with early-stage idiopathic Parkinson’s disease. The primary efficacy variable was the change in the sum of the score from the Activities of Daily Living scale and motor examination in the Unified Parkinson's Disease Rating Scale (UPDRS) from baseline to the end of the maintenance period.

The second phase 3 study was a multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12-week study that evaluated the efficacy and safety of rotigotine (escalating weekly dose starting with daily doses of 4 mg/24 hours to 16 mg/24 hours) in 346 adult patients (30 years and older) with advanced-stage idiopathic Parkinson’s disease who were not well-controlled on levodopa. The primary efficacy variable was the change in absolute time spent "off" from baseline to the end of the double-blind maintenance period.

Results from these studies will be presented at upcoming international congresses. Today, Neupro, a transdermal patch,  is currently available as a treatment for Parkinson’s disease in over 46 countries worldwide, including the US, the European Union and Japan.

Neupro is currently not approved in China for the treatment of Parkinson’s disease.  Parkinson's disease is a progressive and chronic neurological disease characterised by the physical motor symptoms of resting tremor, muscle rigidity and slowness of movement. Symptoms not related to movement (non-motor symptoms) can also occur and include pain, sleep disturbances and depression.  It is estimated that 6.3 million people are living with Parkinson’s disease worldwide. The age of onset is usually over 60 years. Although it is estimated that 1 in 10 people are diagnosed before the age of 50.

Neupro (rotigotine) is approved in the European Union for the treatment of the signs and symptoms of early-stage idiopathic Parkinson’s disease, as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e. over the course of the disease, through to late stages when the effect of levodopa wears off or becomes inconsistent and fluctuations of the therapeutic effect occur (end of dose or on-off fluctuations). Neupro® is also approved in the European Union for the symptomatic treatment of moderate to severe idiopathic Restless Legs Syndrome in adults.

Neupro (rotigotine) is approved in the European Union for the treatment of the signs and symptoms of early-stage idiopathic Parkinson’s disease, as monotherapy (i.e. without levodopa) or in combination with levodopa, i.e.

UCB, Brussels, Belgium (www.ucb.com) is a global biopharmaceutical company focused on the discovery and development of innovative medicines and solutions to transform the lives of people living with severe diseases of the immune system or of the central nervous system. With more than 8500 people in approximately 40 countries, the company generated revenue of € 3.4 billion in 2013.


 http://health.einnews.com/article/248621659/g_XwdqLF8QXEtgzk

MJFF Brokers Industry Consortium to Advance Disease-modifying Therapies

FoxFeed Blog


Posted by  Maggie McGuire, February 04, 2015
MJFF Brokers Industry Consortium to Advance Disease-modifying Therapies
In our pursuit of a cure for Parkinson’s disease, we’re tenacious, resilient, problem solvers. Our unique view of the research landscape and our unbiased dedication to meeting patients’ needs allows the Foundation to lead initiatives that advance progress across the board.
For example, the Parkinson’s Progression Markers Initiative is working toward validated biological markers of PD that will accelerate drug testing, and Fox Trial Finder is connecting research volunteers with clinical studies that desperately need them to evaluate new therapies.
One of the latest on our list of MJFF-led strategies and projects is the LRRK2 Safety Initiative. The Foundation has united three powerhouse pharmaceutical companies for a pre-competitive consortium to characterize the effects of LRRK2 inhibitors and advance these potential disease-modifying medications.
Studies Find Potential Hurdle to Drug DevelopmentMutations in the LRRK2 gene are associated with Parkinson’s disease and cause heightened activity of the LRRK2 protein kinase, which modifies other proteins. Researchers hypothesize that lowering that activity with drug inhibitors could protect brain cells. 
In a paper published today in Science Translational Medicine authors from biotechnology company Genentech and from MJFF share that they observed changes in lung tissue of pre-clinical models after introducing a LRRK2 inhibitor.
“We don’t know if the changes would have a negative effect, but really any modification is a reason to pause and to consider the safety of the therapy for humans,” said Brian Fiske, PhD, MJFF vice president of research programs and an author on the paper.
MJFF Organizes Drug Development Leaders to Move ForwardHowever, we’re not stepping back from LRRK2. This protein remains one of our top priority targets for a therapy to stop or slow Parkinson’s. 
In light of the concerns around LRRK2 inhibitors, MJFF held a meeting with leaders in this field in January 2014. Kinase inhibitors are a familiar class of drugs to pharmaceutical companies, so a handful had compounds against LRRK2 in their pipelines.
Attendees strategized the future of drug development in this area, and key players in the industry — Genentech, Merck and Pfizer — signed on to join the MJFF LRRK2 Safety Initiative. Each member has submitted a different LRRK2 inhibitor compound to an MJFF-chosen neutral site for independent testing, and data is shared across the consortium. By working together, they’re more efficiently growing the field-wide understanding of the safety and impact of LRRK2 inhibitors.
“Research is a business, and it’s unfortunately often competitive,” said MJFF CEO Todd Sherer, PhD. “These companies are truly putting patients first in their collaboration to move drug development projects forward to clinical testing and application for the five million living with Parkinson’s disease.”
“We can learn more and move faster by working together,” said Reina Fuji, VMD, PhD, senior scientist-pathologist at Genentech. “The Michael J. Fox Foundation’s brokerage of this consortium assures its integrity and patient focus. We at Genentech are glad to contribute to research in this area as a part of the LRRK2 Safety Initiative.”

Thursday, February 5, 2015

Biomarkers Show Potential for Parkinson's Diagnosis



HealthDay News
Updated: Feb 4th 2015

new article illustration
WEDNESDAY, Feb. 4, 2015 (HealthDay News) -- Researchers have developed a blood test that they say could help neurologists detect Parkinson's disease and track the illness as it progresses. The study was published online Feb. 2 in the Proceedings of the National Academy of Sciences.
The researchers say they've found two genetic markers that are 90 percent effective at indicating the presence of Parkinson's disease. The markers are related to how the body processes glucose and insulin, study lead author Jose Santiago, a research associate at the Chicago Medical School, told HealthDay.
The team tracked 101 people with Parkinson's and 91 healthy people. They found that gene expression changed significantly over three years in the Parkinson's patients. It's not clear whether Parkinson's causes changes in the genes or if the genes actually contribute to the development of Parkinson's, the researchers said. Both genes are associated with diabetes, and scientists suspect there may be a link between the two diseases.

More research is needed to confirm that the test works, and the researchers would like to make it more accurate. Also, it's not clear how much the test might ultimately cost. "If successful, we expect our findings will translate into a valuable diagnostic tool for Parkinson's disease," study coauthor Judith Potashkin, Ph.D., professor of cellular and molecular pharmacology at the Chicago Medical School, Rosalind Franklin University of Medicine and Science, told HealthDay.

http://health.einnews.com/article/248251407/TJIlMvHGG2gb7-rh

Tips for Parkinson’s Disease Patients Switching from Sinemet or Madopar to Rytary (IPX066)


You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Health Center for Movement Disorders and Neurorestoration. Dr. Okun is also the author of the Amazon #1 Parkinson's Best Seller 10 Secrets to a Happier Life.

The What’s Hot in Parkinson’s disease blog written in April 2013 featured a new extended release dopamine drug called IPX066.  This new dopamine formulation achieved full FDA approval in January 2015.  The drug is now sold under the name Rytary.  At National Parkinson Foundation we frequently hear from Parkinson’s disease patients that current carbidopa/levodopa medication preparations fail to adequately address disease-related symptoms.  In this month’s What’s Hot column we will update you on important information on Rytary, and also offer a few tips for switching.
It is important to understand the reasons that an individual Parkinson’s disease patient may consider an extended release dopamine medication.  The frequently cited medication related problems include:

Medication dosages taking too long to “kick in” and start working
Medication wearing off before the next scheduled medication dose
Severe on-off medication fluctuation periods (e.g. rapid cycling during the day 
ranging from feeling completely on medication to completely off medication)
Dyskinesia (too much movement, usually resulting from too high of a blood level 
of dopamine)
Too many pills

Too many medication dosage intervals (e.g. taking medications every 1-2 hours 
throughout the waking day).
Patients may also have other disease related issues that levodopa preparations will not address, including walking, balance, talking, and thinking issues, but these will likely require a totally different approach than simple levodopa replacement or Rytary.  Dr. Robert Hauser at the National Parkinson Foundation Center of Excellence at the University of South Florida, along with colleagues from 68 North American and European study sites, recently published a paper on a new extended release formulation of carbidopa/levodopa (IPX066 now called Rytary).

The new formulation of carbidopa/levodopa extended release (IPX066/Rytary), is different than its predecessors.  It contains special beads designed to dissolve at different rates within the stomach and the intestines.  The medication capsule was designed to provide longer lasting benefit for patients with Parkinson’s disease.  The randomized study included 393 Parkinson’s disease patients who reported at least of 2.5 hours of “off time,” defined as periods when they felt the medication was not working.  The authors aimed to improve the number of hours of “off time” each day for patients randomized to the new extended release formulation (IPX066/Rytary) as compared to the older and standard regular release carbidopa/levodopa.   The results revealed that the group on extended release formulations took less overall medication dosages (3.6 vs. 5 doses per day); however they also took more total pills. The daily “off-time” improved by over an hour each day in the extended release formulation.  Both medications in this trial were safe and well tolerated.

If we return to the six areas (listed above in bullet points) where Parkinson’s disease patients have been seeking improved medication formulations, Rytary was observed to improve issues in two categories: wearing off between dosages, and improvement by increasing the time interval between dosages.  The results of the current study cannot be widely applied to patients with severe dyskinesia, severe on-off fluctuations, and later stage disease.  The new extended release formulation also increased the total blood-stream levodopa exposure by 30-40% as compared to conventional immediate release levodopa.  Increasing levodopa in the bloodstream is thought to decrease the threshold for dyskinesia, and this has been observed with other Parkinson’s drugs such as Entacapone and Stalevo. Although dosed less frequently, the extended release formulation can require more total pills per day (see FDA conversion table below). The authors of the Rytary study felt that a newer formulation of the same drug, which they anticipate will be used in future clinical practice, would allow for a decrease in pill number.
In a recent interview with the lead author, Dr. Hauser, we addressed some of the important tips for switching to Rytary.

Though it is unknown who the “best” patients in clinical practice will be, it is suspected that
 patients with  bothersome motor fluctuations, and patients taking a minimum of four 25/100
 Sinemet regular or extended  release (or the equivalent Madopar dosing) may be 
reasonable candidates
Patients with motor fluctuations on three doses of Sinemet or Madopar could benefit, but
 satisfactory

 benefit could possibly be obtained by adding a dose of Sinemet or Madopar rather than 
switching to Rytary


There may be select patients who can take a Rytary dose that is approximately three times
 the usual individual Sinemet or Madopar doses, and be able to maintain three times a day 
dosing a least for a period of time (i.e. before disease progression)

Dosages of Rytary are not interchangeable with other levodopa (Sinemet or Madopar) 
products.

The capsules can be opened and the contents sprinkled onto foods such as apple sauce, if
 swallowing problems are present

The most important information for patients and families is to avoid magical thinking when 
switching to the
Rytary formulation of levodopa.  Further dose adjustments will be likely after the initial 
medication switch.

  It will be important for the patient, family, and doctor to discuss the symptoms and optimize 
and tweak dosages and intervals on the Rytary formulation.

The FDA label on Rytary provides a nice chart on general (approximate) recommendations 
for dosage switching.  We have replicated this table directly from the FDA label and provide 
it below.

Patients and families should be excited by the news of this new formulation of carbidopa/levodopa.  However, patients and clinicians should be aware that there are limitations in the use of Rytary, and that caution should be exercised, especially because in select cases dyskinesia may manifest after switching.  Dosages and dosage intervals of any formulation of carbidopa/levodopa, including Rytary, should be carefully adjusted at each clinic visit to address changes in Parkinson’s symptoms.  Patients may also be slightly disappointed that 3-4 capsules of Rytary may need to be taken at each dosage interval. The success or failure of dopamine replacement therapy will always be more dependent on the expert adjusting the therapy than the formulation itself.  The “timing is critical principle” from Parkinson’s Treatment: 10 Secrets to a Happier Life should be considered during dose adjustments for any Parkinson’s disease patient.  It is really positive news that drug manufacturers are now listening to Parkinson’s disease patients, and are trying to address the major concerns, though there is a lot of room for improvement and more formulations in the marketplace.

Selected references:

1: Pahwa R, Lyons KE, Hauser RA, Fahn S, Jankovic J, Pourcher E, Hsu A, O'Connell M, Kell S, Gupta S; APEX-PD Investigators. Randomized trial of IPX066, carbidopa/levodopa extended release, in early Parkinson's disease. Parkinsonism Relat Disord. 2014 Feb;20(2):142-8. doi: 10.1016/j.parkreldis.2013.08.017. Epub 2013 Sep 5. PubMed PMID: 24055014.

2: Hauser RA, Hsu A, Kell S, Espay AJ, Sethi K, Stacy M, Ondo W, O'Connell M, Gupta S; IPX066 ADVANCE-PD investigators. Extended-release carbidopa-levodopa (IPX066) compared with immediate-release carbidopa-levodopa in patients with Parkinson's disease and motor fluctuations: a phase 3 randomised, double-blind trial. Lancet Neurol. 2013 Apr;12(4):346-56. doi: 10.1016/S1474-4422(13)70025-5. Epub 2013 Feb 26. PubMed PMID: 23485610.

3: Hauser RA. IPX066: a novel carbidopa-levodopa extended-release formulation. Expert Rev Neurother. 2012 Feb;12(2):133-40. doi: 10.1586/ern.11.195. Review. PubMed PMID: 22288668.

4: http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/203312s000lbl.pdf

5: Okun MS.  Parkinson’s Treatment: 10 Secrets to a Happier Life.  Createspace, 2013.
Posted: 2/4/2015 9:33:34 AM by Cathy Whitlock
http://www.parkinson.org/Patients/Patients---On-The-Blog/February-2015-(1)/Tips-for-Parkinsons-Disease-Patients-Switching-fr

Potential Parkinson's Drug Too Toxic to Use

NBC-HEALTH NEWS
Feb 5, 2015 NEWS

An experimental drug to treat Parkinson's disease damaged the lungs of monkeys, and it almost certainly would do the same to people, researchers reported Wednesday.
It's unusual for medical journals to report on drugs that fail, but most do fail before they are ever tested in humans. This report, published in the journal Science Translational Medicine, illustrates the pitfalls of drug development.
empty
The vast, scientific plain that potential drugs must survive before reaching human trials is dubbed the "Valley of Death" — and this once-promising drug has likely fallen into it. The National Institutes of Health estimates that as many as 90 percent of experimental drugs never make it to testing in humans.
Reina Fuji of drugmaker Genentech Inc. and colleagues were testing a drug that interferes with a compound called leucine-rich repeat kinase 2 (LRRK2). Mutations in the gene that produces LRRK2 have been linked with Parkinson's disease. The mutations appear to cause overproduction of LRRK2.
The idea was to make a drug that reduces overproduction of LRRK2. It looked good in mice. But when it was tested in monkeys, the drug damaged their lungs.
That might make for "a critical safety liability" for human patients, they concluded.

http://www.nbcnews.com/health/health-news/potential-parkinsons-drug-too-toxic-use-n300241

Wednesday, February 4, 2015

5 Tricks to Move Through Freezing Episodes in Parkinson's Disease

FoxFeed Blog


Posted by  Nancy Ryerson, February 04, 2015
5 Tricks to Move Through Freezing Episodes in Parkinson's Disease
If you've ever experienced gait freezingin Parkinson's disease, you know it can catch you by surprise. “Freezing is the sudden and unpredictable inability to start moving or continue moving," says Rachel Dolhun, MD, one of our MDs on staff. "It can happen anywhere and at any time but walking through doorways and turning around are common triggers. Not only is this frustrating but it can lead to decreased mobility and falls.” 
Our community shared strategies that they've used to get through freezing episodes.
  1. 1. March in place, or imagine or sing a military song.
    2. Count out loud or in your head, or sing a rhythmic melody. If you feel yourself slowing down before a freezing episode, try humming a tune or thinking of a song in your head, then walking along with it.
    3. Aim your next step at a specific spot on the floor. Try picturing a stick in your path that you're stepping over or towards, our community suggests. If there's a part of your home where you tend to freeze often, such as around a corner or in a doorway, place two strips of colored tape in the area to act as a visual cue.
    4. Ask a family member or friend for help. Several commentors said a little bit of encouragement from someone nearby can help get them through an episode.
    5. Try moving in a different direction, such as backwards or from side to side.

Pesticides trigger Parkinson's



,TNN | Feb 4, 2015, 03.33 PM IST
KOLKATA: Have you been consuming vegetables without washing them properly? It could be exposing you to the risk of contracting Parkinson's disease post-60. A study of patients in Kolkata reveals that pesticides in vegetables might be one of the major causes that trigger the debilitating illness characterized by tremor of hands, muscular rigidity and slow, imprecise movements. The city is believed to have 10,000 Parkinson's patients, up from 3000 a decade ago.Pesticides destroy dehydrodenase, an enzyme in the brain that helps to break down harmful aldehyde - waste product generated by normal functioning of the brain. As a result, the harmful wastes remain in the brain, inhibiting the production of dopamine which is directly responsible for the onset of Parkinson's. An international study linking Parkinson's to pesticides spurred researchers at the Institute of Neurosciences Kolkata (INK) to observe local patients. The result has left them worried. "We are yet to launch a full-scale study on this. But primary observations do point to a worrying fact. A vast quantity of pesticide-laden vegetables enter the Kolkata markets and are regularly consumed. Over a period of time, this has obviously affected the brain. It is quite evident from the sharp rise in the number of Parkinson's patients in the city. Even if we consider the rise in Kolkata's population, the increase in the number of patients is quite remarkable," said Hrishikesh Kumar, head of the department of neurology, INK.
According to experts, though Parkinson's disease has not garnered public health attention as much as heart disease and cancer, it has far reaching negative impact on the quality of life of an individual. Globally, around 6.3 million people are known to be suffering from it. The age of onset is usually over 60, but it is estimated that one in 10 are diagnosed before the age of 50, with slightly more men being affected than women. "It is not just detrimental to the physical health and daily activities, Parkinson's also severely affects mental health of the patient. It is very often associated with depression, demoralization, anxiety and psychosis. Considering the debilitating effects of the disease, treatment modalities offering quick and effective solutions to the problem is the need of the hour," said Kumar.
At least one-fifth of the city's Parkinson's cases are believed to have been triggered by pesticides. Rigorous washing should be enough to get rid of them, say experts. But often, even that may not be sufficient, they warn. "Even if you remove the pesticides on the surface, those injected into the vegetables remain. Rinsing them in boiled water doesn't help either for it removes the nutrients from the vegetables. So, the best way is to consume organic vegetables. The problem, of course, is that they are not widely available yet," said Kumar.
A 2006 study conducted in USA claimed that those exposed to pesticides had a 70% higher incidence of contracting Parkinson's.
Direct brain stimulation (DBS) therapy is one of the remedies for Parkinson's. It involves the use of a small, pacemaker-like device that sends electronic signals to an area in the brain that controls movements. These signals block some of the brain messages that cause disabling motor as well as non-motor symptoms. The device is placed under the skin in the chest , while thin wires connect the device to the brain which enables the signals to reach the source of the patient's symptoms.
But Kumar points out that DBS works only in some severe cases of Parkinson's that don't respond well to medicines. "It may not be advisable in early stages, though DBS is an advanced form of treatment, akin to the cardiac pacemaker," said Kumar.

http://health.einnews.com/article/248043920/96bzVYn9rNtNbLOr


Tuesday, February 3, 2015

International Stem Cell Corporation Announces Completion of Cell Bank for Parkinson's Disease Clinical Trial

CARLSBAD, CA--(Marketwired - February 03, 2015



 - International Stem Cell Corporation (OTCQB: ISCO), a California-based biotechnology company developing novel stem cell-based therapies and biomedical products, today announced that the Company has completed manufacturing of the cell bank of clinical-grade human neural stem cells using its patented process for the recently announced phase 1/2a clinical trial in Parkinson's disease. The cell bank contains over 2.6 billion human cells, sufficient to meet the company's foreseeable clinical trial requirements.

"Completing the production of clinical-grade cells using the previously published protocol is one of the final steps before starting our clinical program," said Ruslan Semechkin, Ph.D., ISCO's Chief Scientific Officer. "Because of the complexity involved in manufacturing live human cell products, having our own GMP facility is not only a strategic advantage, but also allows us to control the production costs. We continue to anticipate, subject to regulatory agency approval, beginning the clinical trial in early 2015 and will provide a further update in the near future."
ISCO's master cell bank of human parthenogenetic neural stem cells (ISC-hpNSC) is produced in compliance with current good manufacturing practices (cGMPs) and the chemistry and manufacturing controls (CMC) discussed in the previously reported pre-IND meeting with the FDA. The cells are karyotypically normal hpNSCs and free of measurable contaminants of human or animal origin. The production of hpNSCs from undifferentiated pluripotent human parthenogenetic stem cells in the master cell bank uses qualified reagents and a standardized protocol developed by ISCO. The undifferentiated human stem cells are derived from the parthenogenetic line and were recently cleared by the FDA for use in clinical trials. Each batch of hpNSC is subjected to standardized quality control testing to ensure viability, sterility and appropriate cellular composition before clinical use. The existing master cell bank and current production scale are sufficient to supply our anticipated product needs through pivotal clinical trials. The cell bank was produced at the company's state of the art GMP manufacturing facility located in Oceanside, Calif. 


About human parthenogenetic neural stem cells
ISC-hpNSCs are a novel therapeutic cellular product derived from the Company's proprietary human pluripotent stem cells. Neural stem cells are self-renewing multipotent cells that are precursors for the main cell types of the central nervous system. The ability of ISC-hpNSCs to differentiate into dopaminergic neurons and express brain-protecting neurotrophic factors offers a new opportunity for the treatment of Parkinson's disease. ISCO's preclinical program includes animal studies to assess the safety and tolerability of our novel cell therapy as well as doses ranging efficacy to be used to design the first clinical trial in Parkinson's disease patients.

About International Stem Cell Corporation
International Stem Cell Corporation is focused on the therapeutic applications of human parthenogenetic stem cells (hpSCs) and the development and commercialization of cell-based research and cosmetic products. ISCO's core technology, parthenogenesis, results in the creation of pluripotent human stem cells from unfertilized oocytes (eggs). hpSCs avoid ethical issues associated with the use or destruction of viable human embryos. ISCO scientists have created the first parthenogenetic, homozygous stem cell line that can be a source of therapeutic cells for hundreds of millions of individuals of differing genders, ages and racial backgrounds, with minimal immune rejection after transplantation. hpSCs offer the potential to create the first true stem cell bank, UniStemCell™. ISCO also produces and markets specialized cells and growth media for therapeutic research worldwide through its subsidiary Lifeline Cell Technology (www.lifelinecelltech.com), and stem cell-based skin care products through its subsidiary Lifeline Skin Care (www.lifelineskincare.com). More information is available at www.internationalstemcell.com and companyblog.intlstemcell.com.
To receive ongoing corporate communications, please click on the following link: http://www.b2i.us/irpass.asp?BzID=1468&to=ea&s=0 
  
Forward-looking Statements
Statements pertaining to anticipated developments, the expected timing and results of clinical studies and regulatory filings, the potential benefits of research programs and products, and other opportunities for the company and its subsidiaries, along with other statements about the future expectations, beliefs, goals, plans, or prospects expressed by management constitute forward-looking statements. Any statements that are not historical fact (including, but not limited to statements that contain words such as "will," "believes," "plans," "anticipates," "expects," "estimates,") should also be considered to be forward-looking statements. Forward-looking statements involve risks and uncertainties, including, without limitation, risks inherent in the development and/or commercialization of potential products, regulatory approvals, need and ability to obtain future capital, application of capital resources among competing uses, and maintenance of intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements and as such should be evaluated together with the many uncertainties that affect the company's business, particularly those mentioned in the cautionary statements found in the company's Securities and Exchange Commission filings. The company disclaims any intent or obligation to update forward-looking statements.
Image Available: http://www.marketwire.com/library/MwGo/2015/2/3/11G032159/Images/NSCs_differentiating_into_Neurons-1237073610217.jpg


Contacts:
International Stem Cell Corporation
Simon Craw, Ph.D.
Executive Vice President
Phone: (760) 940-6383
Email:
ir@intlstemcell.com

Media:

Tony Russo, Ph.D.
Phone: (212) 845-4251
Email:
tony.russo@russopartnersllc.com

Martina Schwarzkopf, Ph.D.
Phone: (212) 845-4292
Email:
martina.schwarzkopf@russopartnersllc.com

Monday, February 2, 2015

Protein threshold linked to Parkinson’s Disease




Excess quantities of a specific protein in the brain dramatically increase the chances of so-called “nucleation events” that could eventually result in Parkinson’s Disease, according to a new study.

Finding a cure for Parkinson’s depends on our ability to understand it. For the first time, we have been able to provide a mechanistic description of the initial, molecular events that can ultimately result in the development of the disease
Celine Galvagnion

The circumstances in which a protein closely associated with Parkinson’s Disease begins to malfunction and aggregate in the brain have been pinpointed in a quantitative manner for the first time in a new study.
The research, by a team at the University of Cambridge, identified a critical threshold in the levels of a protein called alpha-synuclein, which normally plays an important role in the smooth flow of chemical signals in the brain.
Once that threshold is exceeded, the researchers found that the chances that alpha-synuclein proteins will aggregate into potentially toxic structures are dramatically enhanced. This process, known as nucleation, is the first, critical step in the chain of events that scientists think leads to the development of Parkinson’s Disease.
The findings represent another important step towards understanding how and why people develop Parkinson’s. According to the charity Parkinson’s UK, one in every 500 people in the UK – an estimated 127,000 in all – currently has the condition, but as yet it remains incurable.
Dr Celine Galvagnion, a Research Associate at St John’s College, University of Cambridge, and the lead author of the study, said: “Finding a cure for Parkinson’s depends on our ability to understand it. For the first time, we have been able to provide a mechanistic description of the initial, molecular events that can ultimately result in the development of the disease.”
The study suggests that the likelihood of an individual developing Parkinson’s is related to a delicate balance between the protein, alpha-synuclein, and the number of synaptic vesicles in their brain. Synaptic vesicles are tiny, bubble-like structures that help to carry neurotransmitters, or chemical signals, between nerve cells. The cell constantly reproduces the vesicles to enable this.
Under normal circumstances, alpha-synuclein plays a pivotal role in the release of these neurotransmitters from one nerve cell to another. It does this by attaching itself to a thin membrane around the synaptic vesicle, known as the lipid bilayer.
When alpha-synuclein binds to lipid vesicles, it folds into a helical shape in order to perform its function. In certain circumstances, however, the proteins on the vesicle surface misfold and stick together. Once this nucleation process has begun, there is then a danger that free protein molecules within the brain cell will come into contact with the misshapen nucleus on the lipid surface. As these combine, they form thread-like chains, called amyloid fibrils, and start to become toxic to other cells. These amyloid deposits of aggregated alpha-synuclein, also known as Lewy-bodies, are the hallmark of Parkinson’s Disease.
Previous research has suggested that overexpression of alpha-synuclein in the brain is somehow associable with the onset of Parkinson’s, and that the interaction of alpha-synuclein with the lipid bilayer could play a role in modulating the development of the disease, but until now it was not clear why this might be the case.
In the new study, the research team simulated the process by which the proteins attach themselves to the vesicles by creating synthetic vesicles in the lab. These were then incubated with different quantities of alpha-synuclein.
The results showed that when the ratio of protein molecules to vesicles exceeds a level of about 100 (a level 10 times higher than that typically found in a human brain), the proteins attaching themselves to the lipid bilayer around a vesicle are too highly concentrated and bunch together on the surface. As a result, the chances of proteins nucleating on the lipid surface are, remarkably, at least a thousand times higher than the chances of two proteins randomly binding together in solution.
“It became clear in our experiment that there are specific conditions in which you can see the aggregation happening, and other conditions in which you don’t,” Galvagnion added. “It turns out that the ratio determines the ability of alpha-synuclein proteins to nucleate. This provides us with a likely explanation of how the initial steps leading to Parkinson’s occur.”
Together, the results provide, for the first time, a mechanistic description of the key role that membrane interactions can play in the initiation of neurodegenerative diseases, including Parkinson’s Disease.
The full report appears in the new issue of Nature Chemical Biology.

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http://www.cam.ac.uk/research/news/protein-threshold-linked-to-parkinsons-disease