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 disease 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 nerve cells. 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 neurodegenerative conditions," 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 neurodegenerative diseases has gradually shifted from ameliorating symptoms 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.
This research was funded by Taube Philanthropies, Koret Foundation, Jean Perkins Foundation, the National Institutes of Health, and the Veterans Administration.
The Journal of Neuroscience is published by the Society for Neuroscience, an organization of nearly 42,000 basic scientists and clinicians who study the brain and nervous system. Longo can be reached at email@example.com. More information on Huntington's disease and neurotrophins can be found on BrainFacts.org.
Kathleen Snodgrass | EurekAlert!
Nanoparticles as a Solution against Antibiotic Resistance?
15.12.2017 | Friedrich-Schiller-Universität Jena
Plasmonic biosensors enable development of new easy-to-use health tests
14.12.2017 | Aalto University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences