Home OMICs Genetic Disorders Stem Cell Therapy Alleviates Muscular Dystrophy Symptoms in Compassionate-Use Study

Stem Cell Therapy Alleviates Muscular Dystrophy Symptoms in Compassionate-Use Study

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A compassionate-use study has generated promising results for the potential treatment of muscular dystrophies using mesenchymal stem cells (MSCs) derived from Wharton’s jelly (WJ), a substance found in the umbilical cord. The study, led by doctors at Klara Medical Center (KMC), Czestochowa, Poland, and reported in STEM CELLS Translational Medicine, found that individuals treated using WJ-MSC exhibited significant improvement in several body muscles, with no serious side effects.

“Administration of WJ-MSCs in neurological indications is controversial; still, this paper shows that cell therapy is a reasonable experimental treatment option, although the eligibility criteria for treatment needs to be optimized,” said Beata Świątkowska-Flis, MD, PhD, neurologist, unit head at KMC’s Polish Center for Cell Therapies and Immunotherapy, and study leader.

Świątkowska-Flis and colleagues reported on the trial in a paper titled, “The use of umbilical cord-derived mesenchymal stem cells in patients with muscular dystrophies: Results from compassionate use in real-life settings,” in which they concluded: “The results are cautiously encouraging, especially because there is no efficient registered treatment.”

Beata Świątkowska-Flis MD, PhD, neurologist, unit head at KMC’s Polish Center for Cell Therapies and Immunotherapy, and study leader [AlphaMed Press]
Muscular dystrophies encompass a group of muscle diseases caused by gene mutations that result in progressive muscle wasting and weakness. This can eventually lead to death from respiratory failure or cardiomyopathy. “There are many kinds of muscular dystrophy, each affecting specific muscle groups, with signs and symptoms appearing at different ages, and varying in severity,” Świątkowska-Flis explained. “Although over 30 unique genes are involved in their pathogeneses, a similar mutation in the same gene may cause a wide range of phenotypes, and distinct genes may be responsible for one identical phenotype. Because of this heterogeneity, pharmacologic treatments are limited.”

Current treatment options include supportive care and drugs. But while steroids are the gold standard in pharmacotherapy, they can have significant side effects, including weight gain, puberty delay, behavioral issues, and bone fractures. “Because proper treatment is limited, there is an urgent need to look for other methods to stop the progress of the disease,” the authors wrote. “Stem cell therapy is a promising option, especially in DMD [Duchenne muscular dystrophy], also known as ‘muscle stem-cell disease’.”

Adult MSCs are primarily isolated from bone marrow (BM), but may also be isolated from placenta, umbilical cord (UC), amniotic fluid, adipose tissue, dental pulp, breast milk, and synovium, the authors explained. Such cells are currently being tested for several indications because of the very wide range of potential mechanisms of action. “In muscular dystrophies, MSCs may act as a therapeutic agent in several ways,” the team noted. These include differentiating into muscle progenitor cells that can fuse with damaged issues and restore expression of dystrophin, secreting immunomodulatory, anti-inflammatory, and other factors that can decrease inflammation and improve other disease features, and improving the neural component of the disease.

Previous studies have also indicated that “MSCs obtained from umbilical cord have many advantages over MSCs isolated from other sources,” the authors wrote. “Although stem cells cannot resolve the underlying genetic conditions, their wide-ranging therapeutic properties may ameliorate the consequences of the involved mutations,” Świątkowska-Flis continued. “Our study describes the clinical outcomes of the compassionate use of WJ-MSCs in patients with muscular dystrophies treated in real-life settings.”

The team’s compassionate use trial involved 22 individuals with varying types of muscular dystrophies. The group was equally divided between male and female, and the median age was 33 years. Each person received 1–5 intravenous and/or intrathecal injections per treatment course in up to two courses every two months. Muscle strength was then assessed by using a set of CQ Dynamometer computerized force meters.

“In the group as a whole, we saw significant improvement in several body muscles, including limb, hip, elbow, and shoulder,” Świątkowska-Flis commented. The authors further reported, “Overall, the individual response to treatment was heterogeneous. In the most successful case, the patient began moving without a crutch, stopped rehabilitation, and rejoined a full-time job … Our study showed objective and significant improvement in muscle strength in 12 patients (54.5%). This amelioration resulted in improved gait in three patients and improved results in a motor scale in another three patients; altogether, in 6 of 22 (27.3%) patients the benefit from the therapy was significant enough to ameliorate their clinical parameters.”

While the trial results are encouraging, the doctors caution that it is “… far too early to determine the position of MSCs in the treatment of dystrophies.” For example, acknowledged Świątkowska-Flis, “we don’t know how long the therapeutic effect will last; it might be that the therapy should be repeated cyclically. Further studies are needed to optimize stem cell therapy both in terms of treatment scheme in a long period and possible synergy with pharmacological drugs and/or rehabilitation. Still, we believe the results are cautiously encouraging, especially in light of no other efficient treatment.”