UAB joins international drug trial for amyotrophic lateral sclerosis

The investigational drug masitinib appears to inhibit parts of the immune system that may be overactive in ALS.

Peter kiNG iNSIDEPeter King, M.D., professor of neurology and principal investigator for the study at UAB.Investigators at the University of Alabama at Birmingham are enrolling patients in an international trial of a promising new drug for amyotrophic lateral sclerosis, or ALS. Preliminary studies reported last year indicate the drug, masitinib, may help prolong overall survival by up to two years.

The new international study will enroll more than 400 patients from countries around the world. UAB will enroll 12-15 individuals with mild, early symptoms of ALS, a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. There is no cure for ALS. This will be the first drug study for ALS at UAB since 2014.

“The 2021 study, which enrolled 394 patients primarily in Europe and South America, showed that masitinib could prolong survival by up to two years as compared with placebo, provided that treatment starts prior to severe impairment of functionality,” said Peter King, M.D., professor in the Department of Neurology, Heersink School of Medicine, and principal investigator for the study at UAB.

The new study will look at masitinib, an oral medication given in concert with the current standard of care, a drug called riluzole. Masitinib inhibits a class of cells called myeloid cells, which includes mast cells, macrophages, neutrophils and microglia, all part of the human immune system.

King, along with co-investigators Mohamed Kazamel, M.D., and Nan Jiang, M.D., Ph.D., who are the co-directors of the UAB ALS clinic, says the immune system may contribute to the progression of ALS by doing its job too well.

“The immune system is complex,” King said. “In ALS, it appears the immune system can be protective in the beginning, but ultimately becomes too active.”

Over the years, King has established a bank of tissues obtained from ALS patients that has allowed him and collaborators to correlate discoveries in animal models with human disease.

“Our work established that there is a robust inflammatory response in peripheral neuromuscular tissues of ALS patients including mast cells, neutrophils and macrophages,” he said. “Masitinib inhibits the action of these inflammatory cells as well as microglia in the central nervous system by targeting the signaling pathway that activates them. The hope is that dampening the inflammatory response may slow down the progression of ALS.”  

King says there is an ongoing debate among researchers in neurodegenerative diseases regarding the role of the immune system. Some wonder whether a flawed immune response can serve to trigger a neurodegenerative disease. Others suggest the immune response does not play a role in the onset of disease but, once activated, can contribute to the acceleration of disease.  

“We have much to learn about ALS and degenerative diseases in general,” King said. “Studies such as the one we are launching will contribute to the overall body of knowledge of ALS, and can provide insight and discovery that could lead to the next advances in our ability to manage and treat these debilitating conditions.” 

ALS was identified in 1869 by French neurologist Jean-Martin Charcot; but it became more widely known internationally in 1939 when it ended the career of one of baseball’s most beloved players, Lou Gehrig. For many years, ALS was commonly known as Lou Gehrig’s disease.

The disease affects motor neurons, which reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. They govern voluntary movements and muscle control. 

ALS causes these motor neurons to degenerate over time until they eventually die. When the motor neurons die, the brain can no longer initiate and control muscle movement. When voluntary muscle action is progressively affected, people may lose the ability to speak, eat, move and breathe.

The study is supported by AB Science, a French pharmaceutical company and manufacturer of masitinib. Individuals interested in enrolling in the study should contact Sandi Mumfrey by calling 205-934-2120 and selecting option 5 for clinical research.