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, says the lead researcher. Because the new therapy uses a molecule already being used in clinical trials for other diseases, it could be used in a clinical trial for Huntington disease within the next one to two years.
“We didn’t expect to see such dramatic changes after administering this therapy,” said Simonetta Sipione, the Principal Investigator “We expected to see improvement, but not complete restoration of motor skills. When we saw this, we were jumping with excitement in the lab. This is very promising and should give hope to those with Huntington disease. I think it’s a treatment that deserves to go to clinical trials because it could have huge potential.”
Those with this inherited brain disorder, where a mutant protein triggers brain cell death causing loss of motor and cognitive skills and eventually death, have slightly lower levels of a brain molecule known as GM1. When U of A medical researchers restored GM1 to normal levels in lab models with the disease, motor skills in the lab models returned to normal within days, said Sipione, a researcher in the Department of Pharmacology and the Centre for Neuroscience, both within the Faculty of Medicine & Dentistry.
Her team’s research was published in the peer-reviewed journal Proceedings of the National Academy of Sciences today.
The molecule used in the lab tests at the U of A was produced both naturally and synthetically through chemical production. This same molecule has been used in clinical trials for the treatment of Parkinson’s and other neurodegenerative diseases, so using this molecule to treat patients with Huntington disease in a small first stage clinical trial could happen relatively quickly. Details are still being worked out about where the trial would take place, but researchers are hoping it will be at the U of A and are in discussions with a University of Alberta Hospital neurologist.
In 1872, the American physician George Huntington wrote about an illness that he called “an heirloom from generations away back in the dim past.” He was not the first to describe the disorder, which has been traced back to the Middle Ages at least. One of its earliest names was chorea,* which, as in “choreography,” is the Greek word for dance. The term chorea describes how people affected with the disorder writhe, twist, and turn in a constant, uncontrollable dance – like motion. Later, other descriptive names evolved. “Hereditary chorea” emphasizes how the disease is passed from parent to child. “Chronic progressive chorea” stresses how symptoms of the disease worsen over time. Today, physicians commonly use the simple term Huntington’s disease (HD) to describe this highly complex disorder that causes untold suffering for thousands of families.
More than 15,000 Americans have HD. At least 150,000 others have a 50 percent risk of developing the disease and thousands more of their relatives live with the possibility that they, too, might develop HD.
Until recently, scientists understood very little about HD and could only watch as the disease continued to pass from generation to generation. Families saw the disease destroy their loved ones’ ability to feel, think, and move. In the last several years, scientists working with support from the National Institute of Neurological Disorders and Stroke (NINDS) have made several breakthroughs in the area of HD research. With these advances, our understanding of the disease continues to improve.
During the research stage, lab models at the U of A were given the GM1 molecule therapy for four weeks. During the first two weeks after the treatment finished, the lab models still had normal motor function. But after that, motor function started to decline and return to pre-treatment levels by the end of the fourth week. So a potential treatment with this molecule would involve repeated treatments over the long-term, says Sipione.
Sipione and her team are continuing their research to see if restored levels of the GM1 molecule can also reverse cognitive damage in lab models with Huntington disease. They hope to publish the results from these tests within one year. It seems the GM1 therapy improves the way neurons work and makes the mutant huntingtin protein less toxic.
“Because of the way it works, we think it will work on cognitive symptoms of the disease too,” says Sipione, a Canada Research Chair Tier 2 in Neurobiology of Huntington disease and an Alberta Innovates-Health Solutions Scholar.
Treatment of Huntington’s disease
At the moment, there is no cure for Huntington’s disease, but there are ways to manage the symptoms.
You may be prescribed medicines to reduce the involuntary movements, and alleviate depression. Mood stabilisers and antipsychotic medicines can also help with some of the emotional disturbances.
Other ways of managing your symptoms include the following.
Speech and language therapists can help improve your communication and help you to swallow.
Dieticians can advise you on adequate calorie and nutrient intake to stop weight loss.
Occupational therapists can provide you with equipment to help you eat, such as non-slip mats and straws, and help make your home safe by adapting it to your needs.
Physiotherapists can help with any balance or musculoskeletal problems.
Counselling and support groups can be helpful, both for you and your family.
The Huntington Society of Canada funded the research and the CEO said she is excited about the promising results.
“The Huntington Society of Canada is proud to support the excellent research of Dr. Sipione,” said Bev Heim-Myers, CEO, Huntington Society of Canada. “Dr. Sipione, for the first time, has demonstrated that in a Huntington disease laboratory model, the treatment reverts the lab model back to normal, not just slightly better.
“It is important to understand that some treatments may work in laboratory models, but not in people. The applicability of the treatment discovered by Dr. Sipione to Huntington disease patients will be determined in clinical trials. We are optimistic that this research demonstrates real potential for a Huntington disease therapy.”
How to Treat Huntington’s Disease
A rare, genetic brain disorder, Huntington’s disease causes brain cells to degenerate and waste away, producing a constellation of physical, cognitive and emotional symptoms. People with Huntington’s disease experience rapid, involuntary, spasmodic movements of their limbs and head, and suffer from memory loss, confusion and personality changes
There is at present no known means of altering the disease process or the fatal outcome. The choreic movements can be controlled by the use of neuroleptic agents, including dopamine receptor blockers such as haloperidol and perphenazine, and presynaptic dopamine depletors such as reserpine. Behavioral disturbances may respond to clozapine.
Using these drugs combined with supervision of the patient’s daily activities allows for management at home during the early stages of the disorder.
Prevention of Huntington’s Disease
Genetic testing for HD remains a personal decision which should be considered very carefully. Although the test may now be technically less complex, the personal implications remain the same and are substantial.
Anyone seeking genetic testing should do so only through programs in which protocols for testing have been submitted to the Huntington’s Disease Society of America, and which are known to have reputable pre-test and post-test counseling programs.
University of Alberta Faculty of Medicine & Dentistry