RNAi Gene Therapy for Neurodegenerative Disorders

Researchers used a viral vector to insert short hairpin RNAs into brain cells of mice suffering from a neurodegenerative disease similar to human Huntington's disease and found that the treated animals showed restored cerebellar morphology and profound improvement in motor coordination.

Investigators at the University of Iowa (Iowa City, USA worked with a line of mice (SCA1) that carried a mutation that caused the development of a polyglutamine-repeat disease similar to human Huntington's disease and spinocerebellar ataxias. In order to correct this syndrome they injected the mice with a modified adenovirus vector, which carried short RNA fragments that were designed to bind to and silence the mutant gene via RNA interference (RNAi).

They reported in the July 4, 2004, online edition of Nature Medicine that the treated mice showed profoundly improved motor coordination, restored cerebellar morphology, and lacked the characteristic ataxin-1 inclusions in Purkinje cells of SCA1 mice.

"This is the first example of targeted gene silencing of a disease gene in the brains of live animals and it suggests that this approach may eventually be useful for human therapies,” said senior author Dr. Beverly Davidson, professor of internal medicine, physiology and biophysics, and neurology at the University of Iowa. "We have had success in tissue culture, but translating those ideas to animal models of disease has been a barrier. We seem to have broken through that barrier.”



Related Links:
University of Iowa