Long-sought treatment for Huntington's disease a step closer to reality

June 20, 2012

A new gene-silencing strategy can reverse core symptoms associated with Huntington's disease, according to a preclinical study published by Cell Press in the June 21st issue of the journal Neuron. 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," says senior study author Don Cleveland of the University of California at San Diego.

Huntington's disease is a fatal condition marked by uncontrolled movements and cognitive and psychiatric problems. It arises from mutations in the huntingtin gene, which cause toxic protein fragments to build up in the brain. Previous preclinical efforts aimed at blocking the production of mutant huntingtin protein have fallen short because they have been directed at a small portion of the brain. "Because huntingtin is widely expressed, targeting multiple brain regions will likely be required for an effective treatment," Cleveland says.

In the new study, Cleveland and his team reduced mutant huntingtin levels across brain regions in several mouse models of Huntington's disease and in nonhuman primates. They achieved a long-lasting drop in huntingtin 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.

The motor performance of treated animals started improving within 1 month and reached normal levels within 2 months. Psychiatric and motor benefits lasted 9 months after treatment, long after mutant huntingtin 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 says.

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.
Kordasiewicz et al.: "Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis."

Cell Press

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.