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

November 26, 2013

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.

Explore further: Breakthrough on Huntington's disease

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.

New clue on the origin of Huntington's disease

August 12, 2013

The synapses in the brain act as key communication points between approximately one hundred billion neurons. They form a complex network connecting various centres in the brain through electrical impulses. New research from ...

Recommended for you

Wiring rules untangle brain circuitry

December 1, 2015

Our brains contain billions of neurons linked through trillions of synaptic connections, and although disentangling this wiring may seem like mission impossible, a research team from Baylor College of Medicine took on the ...

Can physical exercise enhance long-term memory?

November 25, 2015

Exercise can enhance the development of new brain cells in the adult brain, a process called adult neurogenesis. These newborn brain cells play an important role in learning and memory. A new study has determined that mice ...

New insights on how cocaine changes the brain

November 25, 2015

The burst of energy and hyperactivity that comes with a cocaine high is a rather accurate reflection of what's going on in the brain of its users, finds a study published November 25 in Cell Reports. Through experiments conducted ...


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.