A cardinal feature of Huntington's disease - a fatal genetic disease that typically affects patients in midlife and causes progressive death of specific areas of the brain - is the aggregation of mutant
huntingtin protein in cells.
"For the first time, we have been able to successfully deliver inhibitory RNA sequences from stem cells directly into neurons, significantly decreasing the synthesis of the abnormal
huntingtin protein," said Jan A.
A protein called Rhes may goad the protein
huntingtin into killing brain cells in the striatum (SN: 7/4/09, p.
The company expects the topline clinical data will include a summary of clinical safety results, the degree of mutant
huntingtin protein lowering in cerebrospinal fluid and the ratio of total
huntingtin versus mutant
huntingtin protein in CSF to assess wild-type
huntingtin protein.
HD is a debilitating neurodegenerative disease in which patients carry a mutation in the
Huntingtin (mHtt) protein [92, 93].
Caused by a mutation in the gene for a protein called
huntingtin, the disease damages brain cells so that individuals with HD progressively lose their ability to walk, talk and reason.
"For the first time, wc have been able to successfully deliver inhibitory RNA sequences from stem cells directly into neurons, significantly decreasing the synthesis of the abnormal
huntingtin protein," said Jan A.
Under the terms of the new collaboration, Isis will receive funding from CHDI to identify and conduct IND-enabling studies on an antisense drug targeting the
huntingtin gene.
Scientists identified a mutant form of the protein
huntingtin as the culprit in Huntington's disease in 1993.
An especially intriguing finding is the presence of intranuclear inclusion bodies, consisting of amyloid-like fibrils that contain mutant
huntingtin, ubiquitin, synuclein, and other proteins (15,16).