Duchenne muscular dystrophy Report Summary

Duchenne Muscular Dystrophy (DMD) Overview:

• DMD is the most commonly inherited pediatric muscle disorder.
• It is an X-linked genetic progressive and degenerative myopathy characterized by muscle wasting and weakness.
• This can lead to loss of motor functions in puberty, cardiac and respiratory involvement, and premature death.
• DMD occurs due to spontaneous mutations in the dystrophin gene. The disease is caused by a deficiency of dystrophin, a critical protein component of the dystrophin glycoprotein complex (DGC) in skeletal and cardiac muscles.
• A consequence of DGC inefficiency is muscle fragility, contraction-induced damage, necrosis, and inflammation. As a result, fibrous and fatty connective tissue replaces functional myofibers.
• Many patients are restricted to a wheelchair in their early teens and succumb to cardiac/respiratory failure in their twenties.

Current Therapies:

• Diagnosis and appropriate therapy, including pharmacotherapy, rehabilitation, and surgical management, can preserve a child’s ambulation and prolong their functional independence.
• Steroids have been shown to slow the declining course of the disease.
• Medical research is exploring alternative therapeutic approaches, including exon skipping, gene therapy, and cellular therapy.

Stem Cell-Based Therapies:

• Stem cell therapy is considered one of the most promising methods for treating muscular dystrophies.
• Stem cells have the ability for long-term self-renewal and can differentiate into multiple cell lineages.
• Stem cell-based therapies for DMD can proceed via two strategies:
  1. Autologous stem cell transfer: Cells from a DMD patient are genetically altered in vitro to restore dystrophin expression and then re-implanted.
  2. Allogenic stem cell transfer: Cells from an individual with functional dystrophin are transplanted into a dystrophic patient.
• Skeletal muscle damaged by injury or disease can regenerate new muscle fibers. This regeneration mainly depends on satellite cells (SCs), myogenic progenitors localized between the basal lamina and the muscle fiber membrane.
• Clinical trials involving the transplant of SCs have shown encouraging results in treating DMD patients. However, there are challenges such as immune responses toward injected SCs and the rapid death of most SCs post-injection.

Bone Marrow Cells:

• Two main types of stem cells derived from adult bone marrow are hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs).