Carol Jarod and Tawil Bill*

Department of Bioengineering, University of California, Los Angeles (UCLA), USA

*Corresponding Author: Tawil Bill, Department of Bioengineering, University of California, Los Angeles (UCLA), USA.

Received: July 03, 2024; Published: August 28, 2024

Abstract

Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder characterized by progressive muscle degeneration and weakness, primarily affecting young males. Despite extensive research, no cure currently exists for DMD. With a large and expanding DMD treatment market, we expect new therapeutics to take over existing gold standards of therapy and transform patients' prognoses. Existing therapies such as glucocorticoids, physical therapy, cardiac management, and respiratory therapy focus on symptom management and slowing disease progression. Still, there remains a high demand for long-term, effective treatments. Emerging DMD therapies have shown promising results, including gene therapy, exon skipping, and cell transplantation. Additionally, preclinical research in tissue engineering offers the potential for integrating therapeutic cells and bioactive molecules into DMD treatment. However, this field still has many challenges. This review provides an in-depth examination of DMD, including disease pathology, market size and trends, current therapeutic options, and products in clinical trials. We also explore innovative tissue engineering treatments in preclinical stages.

 Keywords: Duchenne Muscular Dystrophy; Dystrophin; Satellite Cells; Gene Transfer; Exon Skipping; Cell Transplantation; Tissue Engineering

References

1. Centers for Disease Control and Prevention. “What is muscular dystrophy?”. Centers for Disease Control and Prevention (2022).
2. Venugopal V and Pavlakis S. “Duchenne Muscular Dystrophy”. In: StatPearls. Treasure Island (FL): StatPearls Publishing; (2024).
3. Heydemann A and Siemionow M. “A Brief Review of Duchenne Muscular Dystrophy Treatment Options, with an Emphasis on Two Novel Strategies”. Biomedicines3 (2023): 830.
4. Duchenne muscular dystrophy (DMD) - diseases. Muscular Dystrophy Association (2021).
5. Duchenne muscular dystrophy - symptoms, causes, treatment: Nord. National Organization for Rare Disorders (2024).
6. S. National Library of Medicine. (n.d.). Duchenne muscular dystrophy: Medlineplus medical encyclopedia. MedlinePlus.
7. Duchenne muscular dystrophy treatment market trends. Market Research Company - Mordor Intelligence TM. (n.d.).
8. Mukund K and Subramaniam S. “Skeletal muscle: A review of molecular structure and function, in health and disease”. Wiley interdisciplinary reviews. Systems biology and medicine1 (2020): e1462.
9. Wilson DGS., et al. “The role of the dystrophin glycoprotein complex in muscle cell mechanotransduction”. Communication Biology 5 (2022): 1022.
10. Gao Q Q and McNally E M. “The Dystrophin Complex: Structure, Function, and Implications for Therapy”. Comprehensive Physiology3 (2015): 1223-1239.
11. Venugopal V, Pavlakis S. “Duchenne Muscular Dystrophy”. [Updated 2023 Jul 10]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing (2024).
12. Duchenne muscular dystrophy. (DMD) | Sarepta Therapeutics. (n.d.-a).
13. Broomfield J., et al. “Life Expectancy in Duchenne Muscular Dystrophy: Reproduced Individual Patient Data Meta-analysis”. Neurology23 (2021): e2304-e2314.
14. Broomfield J., et al. “Life expectancy in Duchenne muscular dystrophy: Reproduced individual patient data meta-analysis”. Neurology (2021).
15. Landfeldt E., et al. “The burden of Duchenne muscular dystrophy: an international, cross-sectional study”. Neurology6 (2014): 529-536.
16. Thayer S., et al. “The Direct Cost of Managing a Rare Disease: Assessing Medical and Pharmacy Costs Associated with Duchenne Muscular Dystrophy in the United States”. Journal of Managed Care and Specialty Pharmacy6 (2017): 633-641.
17. “Duchenne muscular dystrophy drugs market poised for remarkable 39.1% CAGR, set to reach $27.4 billion by 2030 - researchandmarkets.com”. Business Wire (2023).
18. “Duchenne muscular dystrophy market share analysis report 2024”. MarketResearch.biz. (2024).
19. “Therapeutic approaches for your patients with Duchenne Muscular Dystrophy”. Duchenne.com. (n.d.).
20. Patterson G., et al. “Duchenne muscular dystrophy: Current treatment and emerging exon skipping and gene therapy approach”. European Journal of Pharmacology 947 (2023): 175675.
21. “Deflazacort API manufacturers: Suppliers: Exporters”. PharmaCompass.com. (n.d.).
22. Children’s National HospitalChildren’s National HospitalChildren’s National Hospital has ranked as one of the top 10 pediatric hospitals in the nation - with the #1 ranked neonatology program - by U.S. News & World Report for the fifth year in a row. What. (n.d.). FDA approves steroid-like drug for Duchenne Muscular Dystrophy. clinicallab.
23. S. FDA Approves PREVNAR 20®, Pfizer’s 20-valent Pneumococcal Conjugate Vaccine for Infants and Children. Pfizer. (2023).
24. Center for Biologics Evaluation and Research. (n.d.). PNEUMOVAX 23 - pneumococcal vaccine, Polyvalent. U.S. Food and Drug Administration.
25. “Profiling the seven biggest ventilator manufacturers across the world”. NS Medical Devices (2020).
26. Gotadki R. “Global ACE Inhibitors Market Overview”. Market Research Future.
27. Dzierlega K., et al. “Optimization of antisense-mediated exon skipping for Duchenne muscular dystrophy”. Gene Therapy 27 (2020): 407-416.
28. Walsh S. “FDA grants accelerated approval to first drug for Duchenne Muscular Dystrophy”. U.S. Food and Drug Administration (2016).
29. Kahn J. “FDA grants accelerated approval to first targeted treatment for Rare Duchenne muscular dystrophy mutation”. U.S. Food and Drug Administration (2019).
30. Sarepta Therapeutics Announces FDA Approval of AMONDYS 45TM (casimersen) Injection for the Treatment of Duchenne Muscular Dystrophy (DMD) in Patients Amenable to Skipping Exon 45. Sarepta Therapeutics (2021).
31. Sarepta Therapeutics, Inc. “A Gene Transfer Therapy Study to Evaluate the Safety of Delandistrogene Moxeparvovec (SRP-9001) in Participants With Duchenne Muscular Dystrophy (DMD)”. Clinicaltrials.gov (2023).
32. Butterfield R., et al. “One year data from ambulatory boys in a phase 1B, open-label study of Fordadistrogene Movaparvovec (PF-06939926) for Duchenne muscular dystrophy (DMD)”. MDA Clinical and Scientific Conference (2023).
33. “A study to evaluate the safety and tolerability of PF-06939926 gene therapy in Duchenne muscular dystrophy - full text view”. ClinicalTrials.gov (2022).
34. PTC Therapeutics. “Study of Ataluren for Previously Treated Participants With Nonsense Mutation Duchenne/Becker Muscular Dystrophy (nmDBMD) in Europe, Israel, Australia, and Canada”. Clinicaltrials.gov (2020).
35. Michael E., et al. “Long term treatment with ataluren-the Swedish experience”. BMC Musculoskeletal Disorders 1 (2021): 837.
36. Summit Therapeutics. “Proof of Concept Study to Assess Activity and Safety of SMT C1100 (Ezutromid) in Boys With Duchenne Muscular Dystrophy (DMD)”. Clinicaltrials.gov. (2020b).
37. CHU de Quebec-Universite Laval. “Transplantation of Myoblasts to Duchenne Muscular Dystrophy (DMD) Patients”. Clinicaltrials.gov. (2021).
38. Skuk D., et al. “Dystrophin expression in muscles of duchenne muscular dystrophy patients after high-density injections of normal myogenic cells’. Journal of Neuropathology and Experimental Neurology4 (2006): 371-386.
39. Capricor Inc. “HOPE-Duchenne (Halt cardiomyOPathy progrEssion in Duchenne) (HOPE)”. Clinicaltrials.gov. (2018).
40. Allergy and Asthma Consultants, Wichita, Kansas. “Allogeneic Human Umbilical Cord Mesenchymal Stem Cells for a Single Male Patient With Duchenne Muscular Dystrophy (DMD)”. Clinicaltrials.gov. (2019).
41. Assistance Publique - Hôpitaux de Paris. “Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts (OPMD)”. Clinicaltrials.gov. (2015).
42. Lev R and Seliktar D. “Hydrogel biomaterials and their therapeutic potential for muscle injuries and muscular dystrophies”. Journal of the Royal Society, Interface138 (2018): 20170380.
43. Heydemann A., et al. “Dystrophin Expressing Chimeric (DEC) Cell Therapy for Duchenne Muscular Dystrophy: A First-in-Human Study with Minimum 6 Months Follow-up”. Stem Cell Reviews and Reports 19 (2023): 1340-1359.
44. Cossu G., et al. “Intra-arterial transplantation of HLA-matched donor mesoangioblasts in Duchenne muscular dystrophy”. EMBO Molecular Medicine12 (2015): 1513-1528.
45. Klimczak A., et al. “Co-Transplantation of Bone Marrow-MSCs and Myogenic Stem/Progenitor Cells from Adult Donors Improves Muscle Function of Patients with Duchenne Muscular Dystrophy”. Cells 5 (2020): 1119.
46. Fernández-Costa JM., et al. “Bioengineered in vitro skeletal muscles as new tools for muscular dystrophies preclinical studies”. Journal of Tissue Engineering. 12 (2021).
47. Nakayama K H., et al. “Treatment of volumetric muscle loss in mice using nanofibrillar scaffolds enhances vascular organization and integration”. Communications Biology 2 (2019): 170.
48. Yeo M and Kim G. “Micro/nano-hierarchical scaffold fabricated using a cell electrospinning/3D printing process for co-culturing myoblasts and HUVECs to induce myoblast alignment and differentiation”. Acta Biomaterialia 107 (2020): 102-114.
49. Lee H., et al. “A novel decellularized skeletal muscle-derived ECM scaffolding system for in situ muscle regeneration”. Methods (San Diego, Calif.), 171 (2020): 77-85.
50. Denes L T., et al. “Culturing C2C12 myotubes on micromolded gelatin hydrogels accelerates myotube maturation”. Skeletal Muscle1 (2019): 17.
51. Borselli C., et al. “Functional muscle regeneration with combined delivery of angiogenesis and myogenesis factors”. Proceedings of the National Academy of Sciences of the United States of America,8 (2010): 3287-3292.
52. Falco EE., et al. “Porous EH and EH-PEG scaffolds as gene delivery vehicles to skeletal muscle”. Pharmaceutical Research6 (2011): 1306-1316.
53. Rossi C A., et al. “In vivo tissue engineering of functional skeletal muscle by freshly isolated satellite cells embedded in a photopolymerizable hydrogel”. FASEB journal: official publication of the Federation of American Societies for Experimental Biology7 (2011): 2296-2304.
54. Fuoco C., et al. “Injectable polyethylene glycol-fibrinogen hydrogel adjuvant improves survival and differentiation of transplanted mesoangioblasts in acute and chronic skeletal-muscle degeneration”. Skeletal Muscle 2 (2012): 24.
55. Ruvinov E., et al. “The effects of controlled HGF delivery from an affinity-binding alginate biomaterial on angiogenesis and blood perfusion in a hindlimb ischemia model”. Biomaterials16 (2010): 4573-4582.
56. Kankala R K., et al. “Highly Porous Microcarriers for Minimally Invasive In Situ Skeletal Muscle Cell Delivery”. Small (Weinheim an der Bergstrasse, Germany) 15.25 (2019): e1901397.
57. Beier JP., et al. “Tissue engineering of injectable muscle: three-dimensional myoblast-fibrin injection in the syngeneic rat animal model”. Plastic and Reconstructive Surgery5 (2006): 1113-1121.
58. Hwang JH., et al. “Combination therapy of human adipose-derived stem cells and basic fibroblast growth factor hydrogel in muscle regeneration”. Biomaterials 25 (2013): 6037-6045.
59. Ansari S., et al. “Muscle Tissue Engineering Using Gingival Mesenchymal Stem Cells Encapsulated in Alginate Hydrogels Containing Multiple Growth Factors”. Annals of Biomedical Engineering 44 (2016): 1908-1920.

Citation

Citation: Carol Jarod and Tawil Bill. “A Review on Duchenne Muscular Dystrophy - Market Analysis, Existing Products, Clinical Trials, and Preclinical Tissue Engineering Treatments”.Acta Scientific Medical Sciences 8.9 (2024): 125-141.

Copyright

Copyright: © 2024 Carol Jarod and Tawil Bill. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.