Research Scientists and Doctors from universities in the UK, France, Germany, Italy, Belgium, reached these conclusions in 2021 regarding the potential for “genetically corrected” autologous stem cell transfers to mitigate, and cure, DMD patients.
“The possibility to repair mutations in muscle stem cells has become a realistic perspective due to the introduction of the CRISPR/Cas9 system into clinical medicine. Indeed, it can be shown that primary human muscle stem cells can be genetically corrected with almost 100% efficiency (Escobar et al., 2021). An autologous transplant of corrected muscle stem cells has developed into a realistic perspective. (Boyer, et al. p.9)”
“Pathological muscle weakness has enormous implications for the affected individual and for society as a whole, considering that certain diseases are very common. Major therapeutic breakthroughs have not reached clinical routine .” (Boyer et al. p. 9)
“Human adipose-derived stromal cells (hASCs), characterized by the 12 cell surface proteins HLA-DR, HLA-ABC, CD13, CD29, CD31, CD34, CD44, CD45, CD73, CD90, CD105, and CD11, have also been reported to have some beneficial effects. hASCs were systemically administered in the DMD mouse (mdx) and dog (GRMD) models and were shown to be well-tolerated, with good muscle engraftment and some human dystrophin expression (Rodriguez et al., 2005; Vieira et al., 2012; Pelatti et al., 2016” (Boyer et al. p.7)
“The innovative power in academic institutions for the emergence of these new therapies in predominantly rare disease, necessitates public funding of such studies as a vehicle for success and for clinical translation of these valid therapeutic options for today’s unmet medical needs.: (Boyer et al, p 13).
Study
Dmd Patients
Cells
Efficacy
Adverse Events
2007, Italy (a)
5
Allogenic muscle-derived CD133+
No
No
2013, India (b)
125
Autologous Bone Marrow Stem Cells
Yes
No
2014 India (c)
1
Autologous Bone Marrow Stem Cells
Yes
No
2014, Ukraine (d)
27
Autologous Bone Marrow Stem Cells
Yes
No
2018 Turkey (e)
9
Allogenic Wharton jelly cultured Stem Cells
Yes
No
2020, Poland
3
Autologous (siblings, father) cutured Bone Marrow Stem Cells and cultured myogenic cells from muscle biopsy
Yes
No
References
Boyer O, et.al. (2021) Myogenic Cell Transplantation in Genetic and Acquired Diseases of Skeletal Muscle. Front. Genet. 12:702547. doi: 10.3389/fgene.2021.702547
MEMBERS OF THE STUDY GROUP
H. Aldearee, Division of Cell Matrix Biology and Regenerative Medicine, The University of Manchester, United Kingdom; A. Bisson, Department of Immunology & Biotherapy, Rouen University Hospital, Normandy University, Inserm U1234, Rouen, France; L. Bragg, Division of Cell Matrix Biology and Regenerative Medicine, The University of Manchester, United Kingdom; V. Bridoux, Department of Digestive Surgery, Rouen Univesrity Hospital, Rouen, France; R. Duelen, Translational Cardiomyology Laboratory, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; A. Farini, Unit of Neurology, Stem Cell Laboratory, Department of Patophysiology and Transplantation, Centro Dino Ferrari, Università degli Studi di Milano, Fondazione IRCCS Cà Granda Ospedale Maggiore, Policlinico, Milan, Italy; E. Gazzero, Muscle Research Unit, Experimental and Clinical Research Center, a Cooperation between Max-Delbruck-Center for Molecular Medicine in the Helmholtz Association and the Charitè Universitadmedizin Berlin, Berlin, Germany; N. Giarratana, Translational Cardiomyology Laboratory, Department of Development and Regeneration, KU Leuven, Leuven, Belgium; C. Giverne, Department of Immunology & Biotherapy, Rouen University Hospital, Normandy University, Inserm U1234, Rouen, France; L. Meggiolaro, Division of Cell Matrix Biology and Regenerative Medicine, The University of Manchester, United Kingdom; E. Negroni, Sorbonne Université, Inserm, Institut de Myologie, Centre de Recherche en Myologie, Paris, France; E. Porrello, INSpe and Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy; R. Tonlorenzi, INSpe and Division of Neuroscience, IRCCS Ospedale San Raffaele, Milan, Italy; C. Villa, Unit of Neurology, Stem Cell Laboratory, Department of Patophysiology and Transplantation,
Several emerging therapies are significantly changing the way DMD is treated. These include stem cell therapy, stem cell mobilization therapy, and (potentially) gene editing. RaceMD® is concentrating on intermediate DMD therapies that may be applicable now. We are in collaboration with some of the stem cell doctors who are applying current therapies.
Stem Cell Therapy
Stem cells are the building blocks of all cells in the human body. Every cell in our bodies begins as a stem cell and, through a series of genetic signaling, transform into the various cells that make up the human body. In Duchenne, a dysfunction in the stem cell process prevents some of these stem cells from transforming into effective muscle.
Stem cell transplantation offers two types of therapies: allogeneic and autologous.
Allogeneic stem cell transplants are stem cells derived from a donor via bone marrow, muscle fibers, fat tissue, and sometimes umbilical cord blood. The donor's blood must be matched to the recipient to ensure there is no rejection of the stem cells posttransplant.
Autologous stem cell transplants take the patient's own stem cells and reintroduce them into the body. This type of transplant does not pose a risk of rejection since the cells are derived from the patient. Both of these procedures have been performed in Duchenne patients, and both types of stem cells (from donors and from patients) have shown promise in the treatment of Duchenne.
For a synopsis of potential stem cell therapies, please read Dr. Rudnicki, 2016. Extensive stem cell research efforts in India at the Neurogen Brain and Spine Institute have yielded positive results. Dr. Alok Sharma, Executive Director of Neurogen and a global leader in stem cell therapy and Duchenne, has successfully treated over 1,200 Duchenne patients with stem cell therapy and over 800 patients with other dystrophies or other similar illnesses. In Ukraine, approximately 25 DMD patients were also treated with stem cell transplant therapy in clinical trials. France researchers conducted a clinical trial on stem cell transplant therapy for ten throat muscular dystrophy patients. All clinical trials showed positive results.
Stem Cell Mobilization Therapy
Along with stem cell transplantation, granulocyte-colony stimulating factor (G-CSF) has demonstrated promise as another therapeutic option for DMD. Commonly used prior to stem cell extraction, G-CSF has been shown to be therapeutic on its own as well. G-CSF therapy involves the mobilization of a patient's own stem cells via intramuscular injection of the compound without the need for a stem cell transplant. G-CSF stimulates the release of stem cells from bone marrow. In animal models, this allowed more stem cells to reach maturation, resulting in increases in skeletal muscle mass, strength, respiratory function, and more satellite cells. Japan first demonstrated the efficacy of G-CSF therapy for DMD. Poland has initiated clinical trials. Studies in the United States have long explored the safety of G-CSF for a variety of diseases. They conclude that G-CSF can be a safe and effective therapy option for both adult and pediatric use.
Gene Editing
Gene therapy is rapidly advancing the ability to treat Duchenne at a genetic level. DMD is caused in part by a mutation of the gene which produces dystrophin, the protein responsible for building healthy muscle. Researchers in the US, Canada, and Japan have recently found a way to alter the genetic code through exon skipping in order to signal the body to produce functional dystrophin. By skipping the mutated genes, a percentage of DMD patients are able to produce the dystrophin they lack. Separate researchers have used gene-editing techniques known as CRISPR and Falon to correct the genetic errors in animal models of the disease.
For more complete explanations of the research and clinical trial basis for stem cell therapy, please visit the Duchenne Stem Cell Forum.
These therapies are real, effective, and some are available now. Please help us get these lifesaving treatments to the children who will die without them.
Research Library:
Hilal Kalkan(1),et al. , Targeting gut dysbiosis against inflammation and impaired autophagy in Duchenne muscular dystrophy
EMBO Molecular Medicine (2023)
Olivier Boyer (1) et al, Myogenic Cell Transplantation in Genetic and Aquired Diseases of Skeletal Muscles
Frontiers in Genetics (2023)
(a) Torrente et al., Autologous transplantation of muscle-derived CD133+ stem cells in Duchenne muscle patients. Cell Transplant. 2007;16(6):563-77. doi: 10.3727/000000007783465064.
(b) Sharma et al., A clinical study shows safety and efficacy of autologous bone marrow mononuclear cell therapy to improve quality of life in muscular dystrophy patients. Cell Transplant. 2013;22 Suppl 1:S127-38. doi: 10.3727/096368913X672136. Epub 2013 Sep 10.PMID: 24070109.
(c) Sharma et al., Autologous bone marrow mononuclear cell transplantation in Duchenne muscular dystrophy - a case report. Am J Case Rep. 2014 Mar 28;15:128-34. doi: 10.12659/AJCR.890078. eCollection 2014.PMID: 24711886.
(d) Sych et al., Efficacy of Fetal Stem Cells in Duchenne Muscular Dystrophy Therapy. Journal of Neurorestoratology 2014:2 37-46
(e) Dai et al., Efficacy of stem cell therapy in ambulatory and nonambulatory children with Duchenne muscular dystrophy - Phase I-II. Degener Neurol Neuromuscul Dis. 2018 Oct 26;8:63-77. doi: 10.2147/DNND.S170087. eCollection 2018.PMID: 30498389.
(f) Klimczak 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, 2020 Apr 30;9(5):1119. doi: 10.3390/cells9051119.
