January 18, 2008 by mike.

PFP Inc. , in forging “Partnerships for Parkinson’s” has joined with Prodege to create a method of funding the 501 (c) 3 organization through web search engines.

Download the special toolbar at the following site:

http://PartnershipsforParkinsonsPFPInc.prodege.vmn.net/

Install and every time you use the search box a donation is made to PFP Inc!

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January 11, 2008 by mike.

NEW YORK, Jan. 4 /PRNewswire-USNewswire/ — 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.

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.

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January 11, 2008 by mike.

A successful treatment for Parkinson’s disease, a neurodegenerative disorder that affects 1 percent of the world’s population and (an estimated 500,000 people in the U.S.) aged 60 years and over, may be “in our sights now,” says Ronald McKay, a researcher at the National Institutes of Health (NIH).

McKay’s optimism stems from new research that shows that a gene, known as forkhead box A2 (FOXA2), is responsible for the differentiation and spontaneous destruction of neurons that secrete the neurotransmitter dopamine, a cell population that is progressively lost in Parkinson’s disease, which is characterized by tremors, loss of muscle control and speech difficulties.

“We have the cells; we know what controls their birth and death—we’re on our way,” says McKay, a senior molecular biology investigator. “It looks like we’ve got this disease in our sights now. We will understand Parkinson’s disease relatively soon.”

McKay and colleagues (at the NIH’s National Institute of Neurological Disorders and Stroke in Bethesda, Md., and at Northwestern University’s Feinberg School of Medicine in Chicago) report in the journal PLoS Biology that they tested candidate cells in the brain of embryonic mice to determine which ones produce the enzyme tyrosine hydroxylase, a compound manufactured by dopamine neurons to help convert amino acids into precursors of the neurotransmitter.

The team found that such cells are created at the floor plate, a tubular cluster of cells located near the spinal cord, which organizes the developing brain by signaling immature, precursor cells to differentiate into neurons that play a particular role.

“The floor plate gives rise directly to dopamine neurons; it isn’t just an organizer, but it’s also itself a precursor cell,” McKay says.

While examining the floor plate to determine when new dopamine neurons are created (and thereby when tyrosine hydroxylase signals can be detected), researchers also discovered high levels of FOXA2, the transcription factor coded by the FOXA2 gene.

“If you increase the expression [effect] of FOXA2, you get more dopamine neurons in the lab,” McKay says, noting that when they upped the amount of FOXA2 in a tissue culture it triggered the creation of six times as many dopamine-producing nerve cells as normally present.

In addition, researchers observed spontaneous degeneration of dopaminergic neurons in the substantia nigra (a midbrain region associated with both pleasure and movement) in transgenic mice created without the usual two copies of the FOXA2 gene. (Animals normally receive a copy of the gene from each parent.) Substantia nigra nerve cells send dopamine to the striatum, another midbrain structure, which regulates the planning of movement. The erosion of these cells began after the mice turned 18 months old, which is akin to the age at which Parkinson’s most often strikes humans.

Just as in humans, the loss of cells was unequal in the two brain spheres, resulting in asymmetric motor difficulties, such as stiffness on the right side but not the left.

“In the case of Parkinson’s, although we know 10 genes involved in the disease, we don’t have a good experimental model that is like the cell loss that you see in Parkinson patients,” McKay says. “In these animals we do see this, we see a spontaneous loss of the same dopaminergic neurons that are seen in Parkinson’s disease.”

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