Muscular dystrophy (MD) in simple words can be described as a group of muscular diseases which deteriorates the condition of skeletal muscles with the time that is in terms of weakening and breaking of the skeletal muscles. MD may differ on the degree of weakness, where the muscle is primarily being affected and how early is the onset of symptoms. There are a number of people who later claim of losing their ability to walk.
As per the researchers, by removing only one gene from the normal muscle fibers they observed increased growth by three times. Scientists at Washington University School of Medicine in St. Louis have discovered that their research has built a path for the treatment of a rare form of muscular dystrophy.
Muscular dystrophy makes life hectic and struggling from standing up from a seat to brushing one’s hair. This type of muscular dystrophy causes continuous muscle wastage in shoulder and hip region. It later makes them unable to move their arms up and even walk up to a few meters.
This type is called limb-girdle muscular dystrophy. It affects 1 in 14,286 to 1 in 200,000 individuals across the nation.
Like other uncommon diseases, scientists, organizations, and funding agencies tends to ignore it and has not been a major source of attraction, thus the progress towards its treatment is slow. However, a group at Washington University School of Medicine in St. Louis that recognized a subtype of the disease in 2012 has demonstrated that lithium improves muscle size and quality in mice with this type of muscular dystrophy.
The findings were published on April 18 in Neurology Genetics. The new research may in future prompt a drug for this deteriorating condition.
“There are no medications available for people with limb-girdle muscular dystrophy, so we are very excited to have a good therapeutic target and a potential therapy,” said lead author C. Chris Weihl, MD, Ph.D., a lecturer of neurology who helps people with muscular dystrophy at the university’s Neuromuscular Disease Center.
“This has been an amazing project. It all began when we diagnosed a patient with muscular dystrophy of unknown cause. Genetic sequencing then helped us identify a new subtype, and we’ve been able to take that all the way through to a possible therapy.”
Limb-girdle muscular dystrophy can be caused by a group having a variety of up to 12 genes. Weihl and partners – including neurologist Robert Baloh, MD, Ph.D., and Matthew Harms, MD a few years back met two families. Many of the members of the two families had manifestations of the condition, but none of them had the same common known genetic variant.
By investigating the DNA of influenced and unaffected individuals from the two families, the specialists found that a variety in the gene DNAJB6 was in charge of their muscle wastage.
While the specialists had discovered the defective gene, it wasn’t promptly clear why a modification to that gene made individuals’ muscles deteriorate. To discover, Weihl and co-first authors Andrew Findlay, MD, a clinical individual in neurology science, and Rocio Bengoechea Ibaceta, Ph.D., a staff researcher, removed the gene totally, hoping to see considerably more muscle loss when the gene was absent. What they found was totally opposite. The muscle size without DNAJB6 increased thrice to the normal size of the muscle fibers.
“When Drew showed me these enormous muscle fibers, I just didn’t understand it,” Weihl said. “But Drew pointed out that we were on the right pathway, but perhaps going the wrong direction. Something in this pathway is important for muscle growth.”
They repeated their experiment once again but this time using genetically altered mice that Weihl and associates had built in 2015. These mice conveyed a similar genetic variation as the patients, and like the patients, they developed active muscle wastage in adulthood.
Using muscle from these mice, the analysts found that disease variations over-activate a protein that stifles muscle development. Moreover, hindering the protein – called GSK3beta – with lithium chloride improved mice’s health and muscle mass.
“Before treatment, mutant mice had roughly one-fifth the strength of the normal mice,” Findlay said. “After a month of treatment, they improved to 75 percent of the normal mice. It’s a big jump.”
Lithium chloride was once sold as table salt however was removed from the racks in 1949, when specialists found that sprinkling it on nourishment can be fatal. However, different forms of lithium; for example, lithium carbonate and lithium citrate are utilized to treat some mental health issues, so it’s possible that a safe form of lithium could help the patients with muscular dystrophy.
“I don’t want people to go out and take lithium chloride right now,” Findlay said. “We’ve shown that this protein is a promising therapeutic target, but more work needs to be done.”
Before any clinical trial for testing the compound against the protein, a much better understanding of muscular dystrophy is needed. The disease is marked as so rare that up till now scientists despite the medical advancement have not identified how quickly people lose the strength of the muscles and how the course of the disease differs in the individuals on the basis of variation in different genes.
“We’re at a point where therapeutic development has outpaced our understanding of the natural history of this disease,” Weihl said. “We have a therapeutic target, but we don’t fully understand how patients progress when they’re not treated. We need to understand as many people with this rare disease as possible so when we do start testing an investigational drug, we can be confident that it is changing the course of the disease.”
Weihl, Findlay, and associates around the U.S. and, U.K. are further planning to arrange another investigation of individuals with limb-girdle muscular dystrophy brought about by varieties in any gene. The target of this another research will be to track the progress of the disease of the individuals who are going to appear in the future clinical trials.
Members will make yearly visits to the neuromuscular facility to have a proper check up for example by having timed stair climbs. They will also be asked to fill the questionnaire about the daily tasks they can perform.