In work funded in part by The Michael J. Fox Foundation for Parkinson's Research, scientists at Alnylam Pharmaceuticals, Inc., and Mayo Clinic announced new research published in the journal Molecular Neurodegeneration. The new pre-clinical findings demonstrate durable therapeutic silencing of the alpha-synuclein gene when small interfering RNAs (siRNAs), the molecules that mediate RNAi, are administered by direct delivery to the CNS in mice. Alpha-synuclein is believed to play a central role in the development of Parkinson's disease, where the accumulation of excess alpha-synuclein protein has been associated with the cause and/or pathway of the disease. There exists a significant need for disease modifying therapies for the treatment of Parkinson’s disease, with an estimated 1.5 million Americans afflicted with the disease.

“These new data add to a growing body of knowledge on the applications of RNAi therapeutics for the treatment of neurodegenerative disorders,” said David Bumcrot, Ph.D., Director, Research at Alnylam. “Experts believe that reducing the levels of alpha-synuclein in the brain may slow or even halt the progression of Parkinson’s disease and its associated symptoms. To date, no drugs have been identified that are capable of lowering alpha-synuclein levels in the brain. New approaches like RNAi may pave the way for novel disease-modifying medicines for Parkinson’s disease based on direct administration of siRNAs to the central nervous system of patients with this debilitating and incurable disease.”

The published data (Lewis et al., Molecular Neurodegeneration 2008, 3:19 doi:10.1186/1750-1326-3-19) demonstrated that chemically modified siRNAs targeting alpha-synuclein resulted in significant and durable silencing of the gene in mice. An approximately 70% reduction in alpha-synuclein levels was observed in treated mice, as compared to controls. The results also showed that RNAi silencing of alpha-synuclein lasted for up to three weeks and that the effect was not limited to the immediate site of delivery. In these preliminary studies, the synuclein-specific siRNA was found to be well tolerated in the brain after direct CNS administration. These results suggest that RNAi therapeutics may eventually be useful in reducing the over expression of alpha-synuclein in patients with Parkinson's disease.

The study was conducted in collaboration with Mayo Clinic and funded by Mayo Foundation for Medical Education and Research and The Michael J. Fox Foundation (MJFF) under a ‘Target Validation’ grant awarded in 2005. Earlier this year, Alnylam was part of a research team awarded a new $3.8 million grant from MJFF to further develop an RNAi therapeutic for the treatment of Parkinson’s disease. The four-year grant, which is part of the Foundation’s LEAPS (Linked Efforts to Accelerate Parkinson’s Solutions) initiative, was awarded to Alnylam, Mayo Clinic of Jacksonville, Florida, and the Parkinson’s Institute and Clinical Center of Sunnyvale, California.

Alnylam has an agreement with Mayo Clinic whereby Mayo has granted Alnylam an exclusive license to certain patents and know-how. Mayo Clinic and inventors of this intellectual property may receive developmental milestone and/or royalty payments pursuant to this agreement.