Alnylam Reports Pre-clinical Progress with RNAi Therapeutics in Neurological Disease
Feb 7, 2008 13:58:01 (ET)
CAMBRIDGE, Mass., Feb 07, 2008 (BUSINESS WIRE) -- Alnylam Pharmaceuticals, Inc. (ALNY, Trade ), a leading RNAi therapeutics company, announced today the publication of new research in the journal Human Molecular Genetics. The new study, performed in collaboration with scientists Xandra Breakefield, Ph.D., Bakhos Tannous, Ph.D., and Jeffrey Hewett, Ph.D., from Massachusetts General Hospital, describes the silencing of a key gene implicated in early onset torsion dystonia, known as mutant torsinA. Dystonia is a neurological movement disorder in which sustained muscle contractions cause twisting and repetitive movements or abnormal posture. Early onset torsion dystonia affects approximately 1 in 30,000 - 300,000 persons and, in certain ethnic populations, is prevalent at a frequency of 1 in 10,000.
"We are excited by these new data which demonstrate the ability of RNAi therapeutics to readily discriminate between a disease target of interest, such as mutant torsinA, and a closely related gene, such as wild-type torsinA, thereby providing an important approach for the treatment of genetic disorders," said Dinah Sah, Ph.D., Senior Director of Research at Alnylam. "We are encouraged by these results, as well as results we have seen to date with our other neurological RNAi therapeutic programs, such as Huntington's disease, Parkinson's disease, and others."
Patients with early onset torsion dystonia have a single copy of the wild-type torsinA gene and a single copy of the mutant torsinA gene. TorsinA is implicated in the cellular processing of proteins through the secretory pathway and this cellular function is disrupted by mutant torsinA. The newly published data (Hewett et al., Human Molecular Genetics Advance Access published February 7, 2008 doi:10.1093/hmg/ddn032) show that an siRNA potently and selectively silenced mutant torsinA in vitro, with no effect on the wild-type torsinA gene. The silencing of mutant torsinA by siRNA resulted in normalization of protein secretion. In contrast, siRNAs that suppress both the mutant and normal torsinA genes were not effective in restoring protein secretion, and in fact further impaired secretion. These findings demonstrate that selective inhibition of the mutant torsinA gene only is critical for treatment of dystonia, and that such an approach may be possible with RNAi therapeutics.
About RNA Interference (RNAi)
RNAi (RNA interference) is a revolution in biology, representing a breakthrough in understanding how genes are turned on and off in cells, and a completely new approach to drug discovery and development. Its discovery has been heralded as "a major scientific breakthrough that happens once every decade or so," and represents one of the most promising and rapidly advancing frontiers in biology and drug discovery today which was awarded the 2006 Nobel Prize for Physiology or Medicine. RNAi is a natural process of gene silencing that occurs in organisms ranging from plants to mammals. By harnessing the natural biological process of RNAi occurring in our cells, the creation of a major new class of medicines, known as RNAi therapeutics, is on the horizon. RNAi therapeutics target the cause of diseases by potently silencing specific messenger RNAs (mRNAs), thereby preventing disease-causing proteins from being made. RNAi therapeutics have the potential to treat disease and help patients in a fundamentally new way.
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