The results of the independent preclinical study demonstrate that RNA interference (RNAi) therapy can have a beneficial impact on the symptoms and progression of Huntington's Disease (HD).

The study appeared April 5 in the Online Early Edition of Proceedings of the National Academy of Sciences (PNAS) and will be published in the April 19th issue of PNAS. The study reported a significant reduction in the disease-causing HD protein in mice and a significant improvement in the motor functions and neurological abnormalities associated with the disease.

With RNA interference therapy, researchers for the first time have been able to attack the fundamental cause of Huntington's Disease and reduce the protein expression from the disease gene. The study is the first to show that a therapy designed to inhibit protein production has a beneficial effect on the disease symptoms. The study used RNAi to treat a mouse model of HD. Adeno-associated viral (AAV) vectors were used to express the siRNAs (short interfering RNAs) and were directly injected into the brains of the HD mice. Results of the study demonstrated nearly normal movement in the mice and significant improvements in characteristic neurological damage compared to untreated mice. Results also demonstrated that levels of toxic HD protein in siRNA treated mice were reduced to 40 percent of normal levels.

Dr. Beverly Davidson, a member of Sirna's Scientific Advisory Board and senior author on the current PNAS publication, said, "Many of the current approaches aimed at treating HD are indirect and target the symptoms of the disease. RNAi gives us the first opportunity to attack the fundamental problem and reduce protein expression from the disease gene. It is very exciting that a partial reduction in the HD protein is sufficient to produce a very beneficial effect in the animal. It means that we may not have to turn the gene off completely. Our results showed that with a partial reduction, disease progression can be delayed, and possibly prevented if given prior to onset. We are pleased with the study results and excited to collaborate with Sirna Therapeutics to move the technology to clinical trials and commercialization."

In launching its Huntington's Disease program, Sirna Therapeutics formed a research collaboration with Dr. Beverly Davidson, Roy J. Carver Professor in Internal Medicine, at the University of Iowa. As part of the agreement, Sirna in-licensed key patents from the University of Iowa Research Foundation covering neurological disease targets using RNAi technology, including those relating to Huntington's Disease. In January 2005, Sirna also formed a collaboration with Targeted Genetics Corporation (NASDAQ:TGEN) , the leader in AAV vector delivery to combine Sirna's RNAi expertise with a cutting edge delivery technology. Sirna and Targeted Genetics will co-develop an AAV vector-based treatment for Huntington's Disease, sharing development costs and revenues.

Howard Robin, President and Chief Executive Officer of Sirna stated, "This is truly a breakthrough for Huntington's Disease research. Huntington's Disease is a devastating ailment that affects thousands of people for which there is currently no treatment. With this research, Sirna and its partners have taken a major step toward developing an siRNA therapeutic for HD. We are proud to be part of such a landmark study and to collaborate with Dr. Davidson and the University of Iowa."

Dr. Steven Hersch, Associate Professor of Neurology at Massachusetts General Hospital and Harvard Medical School, and chairman of Sirna's Clinical Advisory Board for neurodegeneration commented, "I am highly encouraged by Dr. Davidson's research, as it demonstrates that an siRNA is able to positively impact Huntington's Disease by reducing the disease-causing HD protein production in an animal model. Although much preclinical work remains necessary, the proof of concept threshold has now been crossed that validates siRNA as a potentially potent approach to treating Huntington's disease."

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