Michael J. Fox Foundation Commits up to $3.8 Million to Develop Gene Silencing Neuroprotective Treatment for Parkinson's Disease
The work is being funded under the Foundationís LEAPS (Linked Efforts to Accelerate Parkinsonís 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.
ďAvailable Parkinsonís treatments mask symptoms but do nothing to halt or slow underlying disease progression,Ē said Katie Hood, chief executive officer of MJFF. ďMore and more scientific evidence supports the hypothesis that lowering alpha-synuclein levels in the brain could achieve the so-called ĎHoly Grailí 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 ó making big bets on fresh ideas with potential to impact patientsí quality of life.Ē
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 Parkinsonís 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 Foundationís Target Validation initiative, the LEAPS researchers have demonstrated that targeted siRNAs reduce alpha-synuclein levels in mouse models of Parkinsonís disease. They will now push this work forward by identifying the optimal alpha-synuclein siRNA drug candidate, then establishing efficacy and the ďtherapeutic windowĒ 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 Parkinsonís 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
Donato A. DiMonte, MD, Professor, Director of Basic Research, The Parkinsonís Institute and Clinical Center, Sunnyvale, California ó 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,
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 Parkinsonís Institute: $1.4 million
- Alnylam: $546,000