Researchers have identified a molecule that they suggest may be able to reduce the progression of myotubular myopathy—a severe genetic disease that leads to muscle paralysis from birth and results in death before 2 years of age.

The molecule—tamoxifen, which is already in use to help treat breast cancer—not only greatly reduces the progression of the disease but also boosts life expectancy in animal models by a factor of seven, according to the researchers, from University of Geneva (UNIGE), Switzerland, and University of Strasbourg, France, in a media release.

“Myotubular myopathy is caused by a lack of myotubularin, an enzyme that transforms the lipidic messengers. Without it, the protein known as dynamin 2 accumulates and brings on muscle atrophy,” explains Elinam Gayi, a PhD student in UNIGE’s School of Pharmaceutical Sciences.

“The disease affects the X chromosome in one in 50,000 male infants,” adds Leonardo Scapozza, full professor at the School of Pharmaceutical Sciences at UNIGE’s Faculty of Science. The disease affects only boys, since the second X chromosome in girls generally compensates for the possible mutation of the first.

Although there is no existing treatment for this genetic defect, research in gene therapy is currently underway. “But it will take years before we can come to a conclusion about how effective the clinical trials are,” points out Olivier Dorchies, a researcher in the School of Pharmaceutical Sciences. “That’s why we turned to a molecule that is already authorized for other treatments in humans, in the hope of finding a quicker way to counter this life-threatening disease,” the release continues.

In their study, published in Nature Communications, the scientists administered tamoxifen orally on a daily basis to sick mice with the same symptoms as affected babies, mixing it with their food. Three doses were tested: 0.03 milligrams per kilogram, 0.3 milligrams per kilogram and 3 milligrams per kilogram.

An untreated sick mouse lived for 45 days on average. With the lowest dose, the average life expectancy was 80 days, rising to 120 days with the intermediate dose.

“But with the biggest dose, life expectancy went up to 290 days on average – seven times higher than for an untreated mouse. Some even survived for over 400 days.” Scapozza says. In addition, the progress of the paralysis was slowed down enormously or even completely stopped. Muscular strength was tripled, and it was possible to recover 60% of the muscular deficit between a healthy mouse and a sick mouse.

The scientists began the treatment when the mice developed the first symptoms, namely paralysis of the hind legs at about 3 weeks. However, they have not ruled out that administering the drug earlier might be more efficacious against muscle weakness, the release continues.

“In parallel to our study, a team from the Children’s Hospital of Toronto tested the drug on even younger mice, and the disease did not develop,” Dorchies shares. “The problem is that in humans, myotubular myopathy starts during fetal development, so it’s hard to know whether the total absence of paralysis might be achieved if this molecule is given after birth.”

“Since tamoxifen is already authorized for use in humans, and a clinical trial is underway for Duchenne muscular dystrophy, we’re hopeful that a clinical trial will come on line within a couple of years,” Gayi adds.

[Source(s): University of Geneva, EurekAlert]