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
IONIS-HTTRx is designed to treat patients with HD and is the first and only drug to demonstrate reduction of neurotoxic mutant huntingtin
protein, the underlying cause of HD, in patients.
The association noted above between MNRR1 and huntingtin
, of MNRR1 and cell migration , and of huntingtin
with microtubules , suggests that MNRR1 could be involved in neuronal migration.
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
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).