Arístides López-Márquez
Duchenne muscular dystrophy (DMD) is a genetic neuromuscular disorder considered to be rare (1 in every 3,500–5,000 male births) caused by mutations in the DMD gene, which is responsible for the production of dystrophin, a protein essential for the stability and function of muscle fibres. It mainly affects males, as the DMD gene is located on the X chromosome, of which males have only one copy. The absence or deficiency of dystrophin causes progressive degeneration of the skeletal, cardiac and respiratory muscles, leading to a gradual loss of motor function and systemic complications.
Current therapeutic approaches include the use of corticosteroids to slow the progression of the disease, multidisciplinary supportive care (physiotherapy, rehabilitation, respiratory and cardiological support) and innovative molecular therapies, notably exon-skipping therapies, which aim to partially restore dystrophin production, and gene therapies, designed to introduce functional versions of the gene or microdystrophins into muscle cells. Furthermore, strategies based on gene editing and regenerative medicine are being investigated with the aim of improving muscle function and modifying the long-term course of the disease.
In this regard, the HOPE-3 clinical trial can be considered a cell therapy, as it involves the intravenous infusion of Deramiocel, a treatment based on a suspension of cells derived from allogeneic cardiospheres (CDC), meaning that these cells are derived from individuals other than the patient receiving the treatment. Furthermore, it should be noted that this is the first Phase III clinical trial to evaluate a non-autologous, systemically administered cell therapy for a genetic disorder, as well as the first Phase III registration trial conducted in patients with Duchenne muscular dystrophy (DMD) in the late stages of ambulation and in non-ambulatory patients.
In earlier phases of the trial, in addition to its safety and low toxicity, its efficacy had been verified not only in cardiac tissue but also in skeletal muscle, based on various parameters that were assessed. In this Phase III trial, which specifically measures clinical efficacy in a considerable number of individuals affected by the condition and which is published in the prestigious journal The Lancet, significant improvements were observed after 12 months of treatment in the treated patients compared with those receiving a placebo, for example in the PUL2.0 test, a validated scale for assessing upper limb function in patients with Duchenne muscular dystrophy.
It is particularly interesting that CDC exerts its effect on the target tissue, such as skeletal muscle and cardiac muscle, through the secretion of extracellular vesicles (nanometre-sized particles formed by a lipid bilayer and loaded with specific bioactive RNA), thereby exerting their anti-fibrotic properties and consequently slowing the progression of myopathy, muscle degeneration and the disease itself in general. Another noteworthy aspect of the study is that, unlike other therapeutic strategies which are specific to each mutation in the DMD gene, this approach is much more versatile, as it does not depend on the mutation carried by the affected individual; consequently, the number of patients who can be treated with this therapy is much greater.
In conclusion, it can be stated that this clinical trial, based on an innovative cell therapy, is a highly promising study yielding robust and significant results that reflect a slowing of the disease’s progression; whilst this does not, of course, constitute or can be considered a complete cure for the disease, it opens up a window of opportunity for patients with DMD.