Proposed drug may reverse Huntington's disease symptoms

June 20, 2012
This image shows stained mouse neurons. Credit: Image courtesy of Taylor Bayouth

With a single drug treatment, researchers at the Ludwig Institute for Cancer Research at the University of California, San Diego School of Medicine can silence the mutated gene responsible for Huntington's disease, slowing and partially reversing progression of the fatal neurodegenerative disorder in animal models.

The findings are published in the June 21, 2012 online issue of the journal Neuron.

Researchers suggest the drug therapy, tested in mouse and non-human primate models, could produce sustained motor and neurological benefits in with moderate and severe forms of the disorder. Currently, there is no effective treatment.

Huntington's disease afflicts approximately 30,000 Americans, whose symptoms include uncontrolled movements and progressive cognitive and psychiatric problems. The disease is caused by the mutation of a single gene, which results in the production and accumulation of toxic proteins throughout the brain.

Don W. Cleveland, PhD, professor and chair of the UC San Diego Department of Cellular and and head of the Laboratory of Cell Biology at the Ludwig Institute for Cancer Research, and colleagues infused mouse and primate models of Huntington's disease with one-time injections of an identified DNA drug based on antisense oligonucleotides (ASOs). These ASOs selectively bind to and destroy the mutant gene's molecular instructions for making the toxic .

The singular treatment produced rapid results. Treated animals began moving better within one month and achieved normal motor function within two. More remarkably, the benefits persisted, lasting nine months, well after the drug had disappeared and production of the toxic proteins had resumed.

"For diseases like Huntington's, where a product is tolerated for decades prior to disease onset, these findings open up the provocative possibility that transient treatment can lead to a prolonged benefit to patients," said Cleveland. "This finding raises the prospect of a 'huntingtin holiday,' which may allow for clearance of disease-causing species that might take weeks or months to re-form. If so, then a single application of a drug to reduce expression of a target gene could 'reset the disease clock,' providing a benefit long after huntingtin suppression has ended."

Beyond improving motor and cognitive function, researchers said the ASO treatment also blocked brain atrophy and increased lifespan in mouse models with a severe form of the disease. The therapy was equally effective whether one or both huntingtin genes were mutated, a positive indicator for human therapy.

Cleveland noted that the approach was particularly promising because antisense therapies have already been proven safe in clinical trials and are the focus of much drug development. Moreover, the findings may have broader implications, he said, for other "age-dependent neurodegenerative diseases that develop from exposure to a mutant protein product" and perhaps for nervous system cancers, such as glioblastomas.

Explore further: A step toward controlling Huntington's disease?

More information: Kordasiewicz et al.: "Sustained therapeutic reversal of Huntington's disease by transient repression of huntingtin synthesis." DOI:10.1016/j.neuron.2012.05.009

Related Stories

A step toward controlling Huntington's disease?

June 23, 2011
Johns Hopkins researchers have identified a natural mechanism that might one day be used to block the expression of the mutated gene known to cause Huntington’s disease. Their experiments offer not an immediate cure, ...

'Very promising' treatment for Huntington disease discovered

February 13, 2012
Medical researchers at the University of Alberta have discovered a promising new therapy for Huntington disease that restores lost motor skills and may delay or stop the progression of the disease based on lab model tests, ...

Investigators achieve important step toward treating Huntington's disease

January 19, 2012
A team of researchers at the UC Davis Institute for Regenerative Cures has developed a technique for using stem cells to deliver therapy that specifically targets the genetic abnormality found in Huntington's disease, a hereditary ...

Recommended for you

How a seahorse-shaped brain structure may help us recognize others

December 8, 2017
How do we recognize others? How do we know friend from foe, threat from reward? How does the brain compute the multitude of cues telling us that Susan is not Erica even though they look alike? The complexity of social interactions—human ...

Brain networks that help babies learn to walk ID'd

December 8, 2017
Scientists have identified brain networks involved in a baby's learning to walk—a discovery that eventually may help predict whether infants are at risk for autism.

Why we can't always stop what we've started

December 7, 2017
When we try to stop a body movement at the last second, perhaps to keep ourselves from stepping on what we just realized was ice, we can't always do it—and Johns Hopkins University neuroscientists have figured out why.

Mutations in neurons accumulate as we age: The process may explain normal cognitive decline and neurodegeneration

December 7, 2017
Scientists have wondered whether somatic (non-inherited) mutations play a role in aging and brain degeneration, but until recently there was no good technology to test this idea. A study published online today in Science, ...

Researchers launch atlas of developing human brain

December 7, 2017
The human brain has been called the most complex object in the cosmos, with 86 billion intricately interconnected neurons and an equivalent number of supportive glial cells. One of science's greatest mysteries is how an organ ...

How we learn: Mastering the features around you rather than learning about individual objects

December 7, 2017
A Dartmouth-led study on how we learn finds that humans tend to rely on learning about the features of an object, rather than on the individual object itself.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.