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Injury triggered change in ER calcium of a muscle cell

ER maintains ion balance needed for muscle repair

Injury triggered change in ER calcium of a muscle cell

A new study led by Jyoti Jaiswal, M.Sc., Ph.D., principal investigator at Children’s National Hospital, identifies that an essential requirement for the repair of injured cells is to cope with the extracellular calcium influx caused by injury to the cell’s membrane. Credit: Goutam Chandra, Ph.D.

Physical activity can injure our muscle cells, so their ability to efficiently repair is crucial for maintaining muscle health. Understanding how healthy muscle cells respond to injury is required to understand and treat diseases caused by poor muscle cell repair.

A new study led by Jyoti Jaiswal, M.Sc., Ph.D., principal investigator at Children’s National Hospital, identifies that an essential requirement for the repair of injured cells is to cope with the extracellular calcium influx caused by injury to the cell’s membrane.

This study, published in the Journal of Cell Biology, identifies endoplasmic reticulum (ER) – a network of membranous tubules in the cell – as the site where the calcium entering the injured cell is sequestered. Using limb girdle muscular dystrophy 2L (LGMD2L) patient cells and a model for this genetic disease, the study shows impaired ability of diseased muscle cells to cope with this calcium excess. It also shows that a drug to sequester excess calcium counters this ion imbalance and reverses the diseased cell’s repair deficit.

“The study provides a novel insight into how injured cells in our body cope with calcium ion imbalance during injury,” Dr. Jaiswal explained. “This work also addresses how calcium homeostasis is compromised by a genetic defect that leads to LGMD2L. It also offers a proof of principle approach to restore calcium homeostasis, paving the path for future work to develop therapies targeting this disease.”

According to Dr. Jaiswal, this work also addresses the current lack of understanding of the basis for exercise intolerance and other symptoms faced by LGMD2L patients.

“This study opens the path for developing targeted therapies for LGMD2L and provides a fundamental cellular insight into a process crucial for cell survival,” said Goutam Chandra, Ph.D., research fellow and lead author of this study.

The Center for Genetic Medicine Research at Children’s National is among only a handful across the world to study this rare disease. These findings are unprecedented in providing the mechanistic insights needed to develop treatment for it.

In addition to Dr. Jaiswal and Chandra, the study co-authors include Sreetama Sen Chandra, Ph.D., Davi Mazala, Ph.D., and Jack VanderMeulen, Ph.D., from Children’s National, and Karine Charton, Ph.D., and Isabelle Richard, Ph.D., from Université Paris-Saclay.

Children’s National Health System named as member of the Parent Project Muscular Dystrophy’s (PPMD) Certified Duchenne Care Centers

mitochondria

Children’s National Health System is now part of a growing Duchenne care network, becoming the newest member of the Parent Project Muscular Dystrophy’s (PPMD) Certified Duchenne Care Program.

The certification process to become a Certified Duchenne Care Center (CDCC) was grounded in the idea that comprehensive Duchenne care and services should be available and accessible to as many families as possible. By joining the network of PPMD Certified Duchenne Care Centers and standardizing care, Children’s National’s Neuromuscular Medicine Program is also improving Duchenne research and clinical trials by decreasing variability in care and increasing the quality of clinical trial outcome measures. This results in accelerating the time it takes therapies to reach the patients who need them.

By allowing neuromuscular patients of all diagnoses access to the comprehensive teams of sub-specialists serving the Duchenne population, Children’s National and other PPMD Certified Duchenne Care Centers will improve the care of all patients with neuromuscular diagnoses.

Muscular Dystrophy Association awards grants to two Children’s National scientists

Marshall Hogarth, Ph.D

Marshall Hogarth, Ph.D

James Novak, Ph.D.

James Novak, Ph.D.

Two Children’s National Health System research scientists, Marshall Hogarth, Ph.D. and James Novak, Ph.D., have received Post-Doctoral Development Grants from the Muscular Dystrophy Association (MDA) as part of funding awarded to young, rising researchers who are poised to become independent investigators.

Over the next three years, Hogarth and Novak will be allotted $180,000 each to underwrite their individual research projects.

Hogarth’s research is focused on limb-girdle muscular dystrophy (LGMD), a disease which presents as muscle weakness when patients are in their late teens before rapidly progressing to severe debilitation. The MDA grant will allow Hogarth to continue his research investigating the replacement of muscle with fatty tissue and the role this plays in the late onset and subsequent progression of LGMD in patients.

Novak focuses mainly on researching Duchenne Muscular Dystrophy (DMD), a severely debilitating form of MD, that leads to progressive muscle weakness and respiratory and cardiac failure. Currently, the only Food and  Drug Administration (FDA)  approved treatment for DMD is exon-skipping. The MDA grant will support Novak’s study of the mechanisms that regulate the delivery of exon-skipping drugs in muscle, in order to identify new therapeutic targets and improve drug efficacy for patients with DMD.

While Hogarth and Novak focus on different aspects of neuromuscular disease, both look forward to making significant contributions that lead to overall improvements in the treatment of patients impacted by muscular dystrophy.