Drug combination increases life span of mice with ALS

A new three-drug cocktail used to treat ALS, or Lou Gehrig’s Disease, may increase life span and decrease disease progression according to a study conducted at the Research Institute of the McGill University Health Centre (MUHC). The study, published in today’s issue of Annals of Neurology, is the first to look at this drug combination in a mouse model of ALS. This research was made possible by a partnership led by the Canadian Institutes of Health Research (CIHR), in conjunction with the ALS society of Canada and the Muscular Dystrophy Association of Canada (MDAC).

“Last year, we demonstrated that minocycline, a commonly prescribed antibiotic, on its own reduced disease progression, and delayed death in the ALS mice,” says MUHC neuroscientist and senior author, Dr. Jean-Pierre Julien. “Findings from our current study show that a therapeutic approach based on a combination of minocycline with two other drugs is much more effective in delaying the onset of the disease and in increasing the longevity of the ALS mice.”

“The results are very impressive,” says Dr. Angela Genge, director of the ALS clinic at the Montreal Neurological Institute and Hospital. “The approach that Dr. Kriz and Dr Julien use is uniquely helpful in screening for potentially effective therapies in this cruel, currently incurable disease. Every gain gives us hope for the future.”

“These research results give people who suffer from ALS hope, and show how well CIHR is working,” said Dr. Rémi Quirion, Scientific Director of the Institute of Neurosciences, Mental Health and Addiction of the CIHR. “I have followed and admired Dr. Julien’s work for many years and it is important that the Government of Canada invest in this kind of research.”

“These results provide hope to ALS patients and their families,” says Centre Hospitalier de l’Universite de Montreal (CHUM) ALS clinician Dr. Monique D’Amour. “Because there is little effective treatment for ALS, new drug strategies are necessary. We will have to see if this will work in patients.”

A steadily progressive and fatal neuromuscular disease, ALS erodes a person’s nervous system, eventually leading to paralysis and the inability to speak or swallow. People with ALS usually die within three to five years of diagnosis. Little is known about the cause of ALS and there is no cure. It is a disease of national importance, affecting between 1,500 and 2,000 people in Canada. Two to three Canadians a day die of ALS.

The discovery reported in this paper by Dr. Jasna Kriz, Ms. Geneviève Gowing and Dr. Julien is funded by a unique partnership between the ALS Society of Canada and the Muscular Dystrophy Association of Canada (MDAC). This partnership, in collaboration with the Canadian Institutes of Health Research (CIHR), has funded over $9 million of neuromuscular research since 2000.

“This is very exciting news for the ALS community,” says Helene Vassos, interim National Executive Director for the ALS Society of Canada. “We are pleased that research, funded by our collaborative initiative with the MDAC and CIHR continues to result in important discoveries.”

Dr. Julien, who is also a professor of Neurosciences at McGill University says that Dr. Kriz looked at the effect of combining three different drugs on the disease progression of ALS mice. The three drugs administered include minocyline- an antibiotic with anti-inflammatory properties, riluzole – the traditional ALS drug, and nimodipine – a drug that blocks calcium channels and normally used to treat brain hemorrhage and for prevention of migraine headache. Dr. Kriz compared the life span, muscle strength, nerve cell loss, and inflammatory response in ALS-mice who were fed a regular diet with those given food containing the three-drug cocktail. The mice fed the drug cocktail lived substantially longer, had a delayed onset of neuronal and muscle deterioration. “Our findings demonstrate the merit of a drug combination approach for treatment of a disease with complex degeneration pathways. The three drugs are currently available and we hope that our study will justify a trial on ALS patients,” says Dr. Julien.