Drug could delay onset of Huntington’s disease: UBC researcher
A drug used to treat Alzheimer’s could also potentially help patients with Huntington’s disease, according to the latest research from the University of British Columbia.
The findings open the door to potential new treatments that could delay symptoms of Huntington’s and even possibly reverse damage caused by the inherited disease, said neurologist Dr. Lynn Raymond, a professor in UBC’s department of psychiatry, who presented the research this week at the annual Canadian Neuroscience Meeting in Montreal.
Using mice in the research, the drug memantine, which is currently used in the treatment of moderate-stage Alzheimer’s disease, was successful in delaying the onset of Huntington’s symptoms in the animals.
The drug seemed to “rebalance pathways” in the brains of animals before they even showed symptoms of the disease— “an indication that the neurons are now back into a healthy state,” said Raymond.
Huntington’s disease is a neurodegenerative genetic disorder that causes the progressive breakdown of nerve cells in the brain. Symptoms can vary, but include involuntary jerking muscle movements, cognitive impairments and psychiatric disorders.
According to Raymond’s research, mice with Huntington’s disease symptoms have more of a specific type of glutamate receptor, called an extrasynapatic NMDA receptor, in their brains.
NMDA receptors are important for learning and memory, but when the receptor is extrasynaptic— located outside the synapse, a structure that allows a neuron to connect to another neuron— it can cause brain cells to die.
Raymond said memantine works by blocking the extrasynaptic NMDA receptors.
When the mice drank water containing the drug, even for just two months before they showed any symptoms of the disease, they had improved motor learning and coordination, she said.
“If you keep the dose of memantine low, then it will preferentially just block the ones that are extrasynaptic and leave the ones that are … needed for learning and memory intact,” she said.
Although the research is promising on mice, Raymond said more human clinical trials are needed before the drug can be prescribed to people with Huntington’s disease.
“One thing we found in the mice is that it’s very dose dependent,” Raymond said. “Low doses are good, but as you increase the dose, and it’s not really clear what that threshold really is, you start shutting down all MMDA receptors and you make things worse.”
A pilot study, which Raymond helped carry out, on memantine’s effect on patients who already have Huntington’s disease symptoms was recently completed at UBC, but the study’s data is still in the process of being analyzed, she said.
Raymond is hopeful the results will lead to clinical trials on patients who have tested positive for the gene responsible for the disease but have not yet shown symptoms.
It may be some time, however, before that takes place, she said.
“One of the issues there is that (health regulators) are concerned about trials in people who are clinically healthy,” she said. “That’s one thing that we have to work out.”