Michael J. Fox Foundation Commits up to $3.8 Million to Develop Gene Silencing Neuroprotective Treatment for Parkinson's Disease

Michael J. Fox Foundation
Friday, Jan. 04, 2008
http://www.centredaily.com/business/story/310724.html

NEW YORK, Jan. 4 — The Michael J. Fox Foundation has committed up to $3.8 million for the development of a gene silencing therapeutic to treat Parkinson's disease by reducing expression of the protein alpha-synuclein. A team of researchers led by Matt Farrer, PhD, of Mayo Clinic Jacksonville (Florida) with collaborators at Alnylam Pharmaceuticals and The Parkinson's Institute and Clinical Center will work to optimize a small interfering RNA (siRNA)-based therapeutic that could slow or stop the progression of Parkinson's disease. If successful, the project could result in an entirely new class of drug targeting the alpha-synuclein gene, which has proved difficult to modulate using traditional small-molecule therapeutics.

The work is being funded under the Foundation's LEAPS (Linked Efforts to Accelerate Parkinson's Solutions) 2007 initiative. LEAPS 2007 was funded with a lead gift from the Edmond J. Safra Philanthropic Foundation. The Edmond J. Safra Philanthropic Foundation has been one of the most steadfast supporters of The Michael J. Fox Foundation since its inception.

"Available Parkinson's treatments mask symptoms but do nothing to halt or slow underlying disease progression," said Katie Hood, chief executive officer of MJFF. "More and more scientific evidence supports the hypothesis that lowering alpha-synuclein levels in the brain could achieve the so-called 'Holy Grail' of PD research, a neuroprotective therapy. But no drugs have been identified to date that are capable of reducing alpha-synuclein expression; new approaches are needed. This LEAPS grant is characteristic of how The Michael J. Fox Foundation goes about its work -- making big bets on fresh ideas with potential to impact patients' quality of life."

While its normal function in the brain remains unknown, the accumulation of excess alpha-synuclein has been shown to be the cause of some familial forms of PD. Clinical, genetic and experimental evidence exists to show that alpha-synuclein accumulation in neurons may be a key feature of non-inherited PD as well. Continued research will analyze whether reducing the levels of alpha-synuclein in the brains of people with Parkinson's can slow the progression of the disease.

RNA interference (RNAi) is a natural mechanism present in all cells whereby small RNA molecules (the siRNAs) specifically silence gene expression by the targeted destruction of messenger RNA, the molecule that contains the instructions for protein synthesis.

In previous work funded under The Michael J. Fox Foundation's Target Validation initiative, the LEAPS researchers have demonstrated that targeted siRNAs reduce alpha-synuclein levels in mouse models of Parkinson's disease. They will now push this work forward by identifying the optimal alpha-synuclein siRNA drug candidate, then establishing efficacy and the "therapeutic window" for brain infusion in animal models. If successful, this project could ultimately lead to the development of an alpha-synuclein siRNA candidate drug that, in the future, could be tested in PD patients in Phase I clinical trials.
Advertisement

LEAPS awards, the signature funding initiative of The Michael J. Fox Foundation, are multi-year, multi-million, multi-disciplinary projects addressing questions with significant practical impact on the treatment of Parkinson's disease. Continued funding is dependent on completion of predetermined milestones at specific stages.

In addition to coordinating principal investigator Dr. Farrer, professor of neurogenetics, Department of Neuroscience, Mayo Clinic Jacksonville, this LEAPS team includes:

Jada Lewis, PhD, Assistant Professor, Department of Neuroscience, Mayo Clinic Jacksonville -- Dr. Lewis will hold primary responsibility for optimizing siRNAs in various mouse models of Parkinson's disease.

Donato A. DiMonte, MD, Professor, Director of Basic Research, The Parkinson's Institute and Clinical Center, Sunnyvale, California -- Dr. DiMonte, an expert in primate neurology, will hold ultimate responsibility for demonstrating that the candidate siRNAs are neuroprotective in primate models of PD.

David A. Bumcrot, PhD, Director, Research, Alnylam Pharmaceuticals, Cambridge, Massachusetts -- Dr. Bumcrot will spearhead the design and synthesis of all candidate siRNAs and lead efforts on investigating siRNA delivery strategies.

While many LEAPS projects involve commercial entities, funds are for stated projects only, dependent upon completion of predetermined milestones at specific stages, and do not represent equity investments. If all milestones are met, this LEAPS allocation will be as follows (rounded figures):

-- Mayo Clinic: $1.9 million

-- The Parkinson's Institute: $1.4 million

-- Alnylam: $546,000

About The Michael J. Fox Foundation

Founded in 2000, The Michael J. Fox Foundation for Parkinson's Research is dedicated to ensuring the development of a cure for Parkinson's disease within this decade through an aggressively funded research agenda. The Foundation has funded approximately $110 million in research to date.

That's a good-looking research collaboration and press release. Anyone else feel like the good guys just made a move or is it just me? Watching things change, and also having hope that the political candidates may not actually get to the name calling stage [one can have hope in other areas too], gives me a warm, hopeful feeling.

Thelma is back. Synergy is in the air.

GO HARD TEAM
paula

It seems serious and promising. Also I can understand what they are trying to do !!!!!!!!!!

imark,
exactly - understandable language.

paula

Thank you! I have high hopes for RNA interference. It's a very exciting field, and brilliant researchers are doing fantastic hard work. Thank you, Michael!

..hence the hope that the attack on it will work .. below is new evidence:
http://www.newsnetnebraska.org/vnews.../478bdd54b616b
News : National News


UNMC Scientists Make Advances in Parkinson's Disease

by Ethan Hamilton, Samatha Mosley and Catherine Lehn
January 14, 2008

New journal articles published by scientists at the University of Nebraska Medical College detailed their findings of causes and the progression of Parkinson's disease according to a UNMC press release. This will allow scientists to work towards more efficient treatments, therapies and vaccines for the disease that affects nearly one million Americans.

"Our research presents conclusive evidence through four stories in mice and using human autopsy tissue that nitrated alpha-synuclein induces toxic inflammatory effects, which are detrimental to healthy neurons. It also incites elements of the immune system in and outside the brain," said R. Lee Mosley, Ph.D., co-investigator for these studies and an assistant professor of pharmacology and experimental neuroscience at UNMC.

In the brains' of Parkinson's patients, nerve cells die which results in a reduced amount of dopamine. The loss of dopamine causes loss of motor skills and tremors.

Although the cause of Parkinson's disease is unknown, scientists have discovered mutations in alpha-synucein, a brain protein. This brain protein helps cells communicate. When the protein is altered in Parkinson's disease patients, the functionality of alpha-synucein changes due to local inflammatory responses.
Researchers at UNMC discovered when the alpha-synuclein is modified, its support function deteriorates. In addition, the disease weakens the immune system which allows Parkinson's disease to accelerate.

"Many scientists had previously thought that alpha-synuclein engagement of the immune system would inhibit Parkinson's disease progression because of antibodies produced against the protein would serve to break down the insoluble proteins formed when alpha-synuclein becomes modified," said Dr. Howard Gendelman, chairman of the pharmacology and experimental neuroscience and director of the Center for Neurovirology and Neurodegenerative Disorders at UNMC. "But this same protein also increases immune reactions that prove toxic to the brain in so doing speed the disease."
Dr. Howard Gendelman, chairman of the pharmacology and experimental neuroscience and director of the Center for Ueurovirology and Neurodegenerative Disorders at UNMC. Courtesy of www.unmc.edu