Drug reduces brain changes, motor deficits associated with Huntington's disease

A drug that acts like a growth-promoting protein in the brain reduces degeneration and motor deficits associated with Huntington's disease in two mouse models of the disorder, according to a study appearing November 27 in the Journal of Neuroscience. The findings add to a growing body of evidence that protecting or boosting neurotrophins—the molecules that support the survival and function of nerve cells—may slow the progression of Huntington's disease and other neurodegenerative disorders.

Huntington's is a brain disorder characterized by the emergence of decreased motor, cognitive, and psychiatric abilities, most commonly appearing in the mid-30s and 40s. The disease is caused by a genetic mutation that leads to abnormal clumps of protein in the brain, eventually resulting in the atrophy and death of . While there are drugs to alleviate some symptoms of the disease, there are currently no therapies to delay the onset or slow its progression.

Previous studies of people with Huntington's disease point to a link between low levels of a neurotrophin called brain-derived neurotrophic factor (BDNF) and symptoms of the disorder. In the current study, Frank Longo, MD, PhD, and others at Stanford University, tested LM22A-4, a drug that specifically binds to and activates the BDNF receptor TrkB on nerve cells, in mice that model the disorder. They found LM22A-4 reduces abnormal protein accumulation, delays nerve cell degeneration, and improves motor skills in the animals. The findings support other recent rodent studies that showed drugs that enhance the action of BDNF can reduce brain changes and symptoms of Huntington's disease.

"These results strongly suggest that drugs that act, in part, like BDNF could be effective therapeutics for treating Huntington's disease and other ," Longo said.

How quickly the symptoms of Huntington's disease progress in people vary greatly. Longo's group examined the effects of LM22A-4 treatment in mice that were predisposed to develop symptoms of Huntington's disease rapidly (within weeks) or gradually (within months). LM22A-4 treatment reduced the accumulation of abnormal proteins in the striatum and cortex—brain regions affected in Huntington's disease. Motor behaviors (downward climbing and grip strength) also improved in the mice that received LM22A-4 treatments daily.

"The search for treatments that slow the progression of has gradually shifted from ameliorating to finding agents that reduce the progression of the disease," said Gary Lynch, PhD, who studies neurodegeneration at the University of California, Irvine, and was not involved with this study. "Given that this drug is clinically plausible, these results open up exciting possibilities for treating a devastating neurodegenerative disease," he added.

Related Stories

Breakthrough on Huntington's disease

May 23, 2013

Researchers at Lund University have succeeded in preventing very early symptoms of Huntington's disease, depression and anxiety, by deactivating the mutated huntingtin protein in the brains of mice.

Research offers clue to halt Huntington's disease

Mar 25, 2011

(PhysOrg.com) -- Surprising findings from a study into the brains of transgenic mice carrying the Huntington's disease mutation could pave the way for treatments which delay the onset and progression of this devastating genetic ...

Recommended for you

'Trigger' for stress processes discovered in the brain

6 hours ago

At the Center for Brain Research at the MedUni Vienna an important factor for stress has been identified in collaboration with the Karolinska Institutet in Stockholm (Sweden). This is the protein secretagogin ...

New research supporting stroke rehabilitation

Nov 26, 2014

Using world-leading research methods, the team of Dr David Wright and Prof Paul Holmes, working with Dr Jacqueline Williams from the Victoria University in Melbourne, studied activity in an area of the brain ...

User 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.