A commonly prescribed muscle relaxant may help treat a rare form of diabetes, researchers at Washington University in St. Louis have found.
According to a news release, the drug— dantrolene— halts the destruction of insulin-producing beta cells in animal models of the disease and in cell models drawn from people who have the illness.
Patients who have the disease, called Wolfram syndrome, usually develop Type 1 diabetes at a young age and must receive multiple daily insulin injections. Diabetes disables the body from producing and properly using insulin, a hormone that helps convert sugar into energy for normal body function, according to the Centers for Disease Control and Prevention (CDC). This effect causes sugar to build up in the blood, which can lead to heart disease, kidney failure and other serious health problems.
In addition to Type 1 diabetes, patients with Wolfram syndrome also have difficulty with balance and hearing and vision loss. One in 500,000 people have Wolfram syndrome, and many patients die by age 40.
During their study, researchers discovered that high levels of the enzyme calpain 2 were the main cause of death in brain cells and insulin-producing cells. Dantrolene, the muscle relaxant, blocked that enzyme and prevented brain cell death in the animals and human-derived models.
Researchers studied the effects of dantrolene on stem cells from Wolfram syndrome patients and their close relatives. The stem cells were grown from skin cells, rather than gathered from cord blood or stem cells developed from embryos. According to the news release, the study authors treated the stem cells in growth factors so they would differentiate into specific cell types, such as neurons and insulin-producing cells. They found that dantrolene wasn’t toxic to cells grown from the skin samples of patients’ relatives.
“The drug interfered with cell death in cells from Wolfram patients but did not harm cells that came from parents and siblings,” senior investigator Fumihiko Urano, a medicine professor at Washington University, said in the news release.
Dantrolene is often prescribed to patients with multiple sclerosis as a treatment for muscle spasticity. The drug has already been approved by the Food and Drug Administration (FDA), so researchers hope to begin clinical trials quickly.
“We’d like to test the drug first in adult patients with Wolfram syndrome, and if we get positive results, we could extend the trial to children,” Urano said.
If dantrolene proves effective in patients with Wolfram syndrome, it may also have the potential to treat other forms of diabetes, like Type 2 diabetes, which accounts for up to 95 percent of diabetes cases, according to the CDC. Calpain 2, which is involved in calcium metabolism, is overactive in cell models of more common forms of diabetes.
“Currently, we are studying the drug in animal and cell models of those types of diabetes to see if it also keeps insulin-producing cells from dying,” Urano said.
The study is published in the Nov. 24 online early edition issue of the journal Proceedings of the National Academy of Sciences.