June 21, 2012
Treatment for Huntington’s Closer To Reality
(Ivanhoe Newswire) — More than 15,000 Americans have Huntington´s disease, a fatal condition marked by uncontrolled movements and cognitive and psychiatric problems. Currently, there are no available treatments to alter the effects of Huntington´s disease, but a new study brings researchers one step closer to finding one.
A new gene-silencing strategy can reverse core symptoms associated with Huntington's disease, according to a preclinical study. The short-term therapy produced sustained benefits in both mouse and primate animal models of this neurodegenerative disorder, which currently lacks an effective treatment.
"Our approach is feasible for development now into a therapy for Huntington´s disease in man," Senior study author Don Cleveland of the University of California in San Diego was quoted as saying.
Previous preclinical efforts aimed at blocking the production of mutant Huntington protein have fallen short because they have been directed at a small portion of the brain.
"Because Huntington is widely expressed, targeting multiple brain regions will likely be required for an effective treatment," Cleveland was quoted as saying.
In the new study, Cleveland and his team reduced mutant Huntington levels across brain regions in several mouse models of Huntington's disease and in nonhuman primates. They achieved a long-lasting drop in Huntington levels through the transient, one-time infusion of single strands of DNA–called antisense oligonucleotides (ASOs)–which selectively bind to and degrade molecules that contain instructions for making the mutant protein.
Effective results began as early. The motor performance of treated animals started improving within one month and reached normal levels within two months. Psychiatric and motor benefits lasted nine months after treatment, long after mutant Huntington levels began to rise again.
"This finding has implications more broadly for therapy in any of the age-dependent neurodegenerative diseases that develop from prolonged exposure to a mutant protein," Cleveland was quoted as saying.
Moreover, the therapy blocked brain atrophy and increased lifespan in mutant mice with a severe form of the disorder. Because ASOs have proven to be safe in clinical trials, with one approved drug and dozens under development, this approach is promising not only for Huntington's disease, but also for other neurodegenerative disorders with a known genetic cause.
SOURCE: Cell Press June 2012