Autologous Bone Marrow Mononuclear Cell Transplantation Improves Function in a Case of Becker’s Muscular Dystrophy
Author(s)
Jasbinder Kaur , Alok Sharma , Hemangi Sane , Nandini Gokulchandran , Amruta Paranjape , Jayanti Yadav , Prerna Badhe ,
Download Full PDF Pages: 01-12 | Views: 804 | Downloads: 188 | DOI: 10.5281/zenodo.3441704
Abstract
Becker’s muscular dystrophy (BMD) is a genetic disorder characterized by progressive muscle degeneration and weakness with no definite cure. Cell therapy is emerging as a promising treatment option for BMD. Autologous bone marrow derived mononuclear cells (BMMNCs) transplantation has been shown to be safe and effective in previous pre-clinical studies. We treated a 21 year old boy suffering from BMD with autologous bone marrow mononuclear cells intrathecal as well as intramuscular transplantation. Pre-therapy clinical assessment showed reduced muscle power in all four limbs and trunk. He was modified independent for all the activities of daily living (ADLs) and scored 102 on Functional Independence Measure (FIM). Musculoskeletal Magnetic Resonance Imaging (MRI-MSK) revealed severe muscular atrophy and fatty replacement in the muscles. Repeat clinical assessment at follow up revealed maintained muscle power along with improvement in some muscles. North Star Ambulatory Assessment score and FIM score was maintained for over nineteen months. Repeat MRI-MSK revealed no increase in fatty infiltration in the muscles indicating halting of the progression of the disease. Thus, this report suggests the role of BMMNCs transplantation in stabilizing the condition of BMD patients. Larger clinical trials with scrupulous methodology may be suggested
Keywords
Becker’s muscular dystrophy, cell therapy, Musculoskeletal Magnetic Resonance Imaging, Functional Independence Measure, autologous, bone marrow, mononuclear cells
References
i. Koenig M, Beggs AH, Moyer M, Scherpf S, Heindrich K, Bettecken T, Meng G, Müller CR, Lindlöf M, Kaariainen H, et al. The molecular basis for Duchenne versus Becker muscular dystrophy: correlation of severity with type of deletion. Am J Hum Genet. 1989;45(4):498-506.
ii. Johnson EK, Li B, Yoon JH, Flanigan KM, Martin PT, Ervasti J, Montanaro F. Identification of new dystroglycan complexes in skeletal muscle. PLoS One. 2013;8(8):e73224.
iii. Sarnat HB. Muscular dystrophies. In: Kliegman RM, Stanton BF, St. Geme J, Schor N, Behrman RE. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011
iv. Finsterer J, Stöllberger C. Cardiac involvement in Becker muscular dystrophy. Can J Cardiol. 2008;24(10):786-92.
v. Leibowitz D, Dubowitz V. Intellect and behaviour in Duchenne muscular dystrophy. Dev Med Child Neurol. 1981;23(5):577-90.
vi. van Ruiten HJ, Straub V, Bushby K, Guglieri M. Improving recognition of Duchenne muscular dystrophy: a retrospective case note review. Arch Dis Child. 2014;99(12):1074-7.
vii. Kerr R, Robinson C, Essop FB, Krause A. Genetic testing for Duchenne/Becker muscular dystrophy in Johannesburg, South Africa. S Afr Med J. 2013;103(12 Suppl 1):999-1004.
viii.Wokke BH, van den Bergen JC, Versluis MJ, Niks EH, Milles J, Webb AG, van Zwet EW, Aartsma-Rus A, Verschuuren JJ, Kan HE. Quantitative MRI and strength measurements in the assessment of muscle quality in Duchenne muscular dystrophy. Neuromuscul Disord. 2014;24(5):409-16.
ix. Manzur AY, Muntoni F. Diagnosis and new treatments in muscular dystrophies. J Neurol Neurosurg Psychiatry. 2009;80(7):706-14.
x. Fujita R, Tamai K, Aikawa E, Nimura K, Ishino S, Kikuchi Y, Kaneda Y. Endogenous mesenchymal stromal cells in bone marrow are required to preserve muscle function in mdx mice. Stem Cells. 2015;33(3):962-75.
xi. Jeong J, Shin K, Lee SB, Lee DR, Kwon H. Patient-tailored application for Duchene muscular dystrophy on mdx mice based induced mesenchymal stem cells. Exp Mol Pathol. 2014;97(2):253-8.
xii. Meng J, Chun S, Asfahani R, Lochmüller H, Muntoni F, Morgan J. Human skeletal muscle-derived CD133(+) cells form functional satellite cells after intramuscular transplantation in immunodeficient host mice. Mol Ther. 2014;22(5):1008-17.
xiii.Pang RQ, He J, Zhang YY, Xiong F, Ruan GP, Zhu XQ, Wang Q, Wang JX, Zhu GX, Zhao J, Cai XM, Pan XH, Zhang C. Systemic delivery of human bone marrow embryonic-like stem cells improves motor function of severely affected dystrophin/utrophin-deficient mice. Cytotherapy. 2014;16(12):1739-49.
xiv.Sharma A, Sane H, Badhe P, Gokulchandran N, Kulkarni P, Lohiya M, Biju H, Jacob VC. 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.
xv. Yang XF, Xu YF, Zhang YB, Wang HM, Lü NW, Wu YX, Lü X, Cui JP, Shan H, Yan Y, Zhou JX. Functional improvement of patients with progressive muscular dystrophy by bone marrow and umbilical cord blood mesenchymal stem cell transplantations. Zhonghua Yi Xue Za Zhi. 2009;89(36):2552-6.
xvi.Sharma A, Paranjape A, Sane H, Bhagawanani K, Gokulchandran N, Badhe P. Cellular Transplantation Alters the Disease Progression in Becker's Muscular Dystrophy. Case Rep Transplant. 2013;2013:909328.
xvii. Sharma A, Sane H, Paranjape A, Badhe P, Gokulchandran N, Jacob V. Effect of Cellular Therapy seen on Musculoskeletal Magnetic Resonance Imaging in a Case of Becker’s Muscular Dystrophy. Journal of Case Reports 2013;3(2):440-447.
xviii. R. V. Carlson, K. M. Boyd, and D. J. Webb. The revision of the declaration of Helsinki: past, present and future. British Journal of Clinical Pharmacology, vol. 57, no. 6, pp. 695–713, 2004.
xix.R. Haas, S. Murea. The role of granulocyte colony-stimulating factor in mobilization and transplantation of peripheral blood progenitor and stem cells. Cytokines and Molecular Therapy, vol. 1, no. 4, pp. 249–270, 1995.
xx. Ramadasan-Nair R, Gayathri N, Mishra S, Sunitha B, Mythri RB, Nalini A, Subbannayya Y, Harsha HC, Kolthur-Seetharam U, Srinivas Bharath MM. Mitochondrial alterations and oxidative stress in an acute transient mouse model of muscle degeneration: implications for muscular dystrophy and related muscle pathologies. J Biol Chem. 2014;289(1):485-509.
xxi.Collins CA, Olsen I, Zammit PS, Heslop L, Petrie A, Partridge TA, Morgan JE. Stem cell function, self-renewal, and behavioral heterogeneity of cells from the adult muscle satellite cell niche. Cell. 2005;122(2):289-301.
xxii. Ceafalan LC, Popescu BO, Hinescu ME. Cellular players in skeletal muscle regeneration. Biomed Res Int. 2014;2014:957014.
xxiii. Wilschut KJ, Ling VB, Bernstein HS. Concise review: stem cell therapy for muscular dystrophies. Stem Cells Transl Med. 2012;1(11):833-42.
xxiv. Doyonnas R, LaBarge MA, Sacco A, Charlton C, Blau HM. Hematopoietic contribution to skeletal muscle regeneration by myelomonocytic precursors. Proc Natl Acad Sci U S A. 2004;101(37):13507-12.
xxv. Neirinckx V, Coste C, Rogister B, Wislet-Gendebien S. Concise review: adult mesenchymal stem cells, adult neural crest stem cells, and therapy of neurological pathologies: a state of play. Stem Cells Transl Med. 2013;2(4):284-96.
xxvi. Sharma A, Gokulchandran N, Chopra G, Kulkarni P, Lohia M, Badhe P, Jacob VC. Administration of autologous bone marrow-derived mononuclear cells in children with incurable neurological disorders and injury is safe and improves their quality of life. Cell Transplant. 2012;21 Suppl 1:S79-90.
xxvii. Linero I, Chaparro O. Paracrine effect of mesenchymal stem cells derived from human adipose tissue in bone regeneration. PLoS One. 2014;9(9):e107001.
xxviii. Gnecchi M, Zhang Z, Ni A, Dzau VJ. Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 2008;103(11):1204-19.
xxix. Geng J, Peng F, Xiong F, Shang Y, Zhao C, Li W, Zhang C. Inhibition of myostatin promotes myogenic differentiation of rat bone marrow-derived mesenchymal stromal cells. Cytotherapy. 2009;11(7):849-63.
xxx. Gnecchi M, He H, Noiseux N, Liang OD, Zhang L, Morello F, Mu H, Melo LG, Pratt RE, Ingwall JS, Dzau VJ. Evidence supporting paracrine hypothesis for Akt-modified mesenchymal stem cell-mediated cardiac protection and functional improvement. FASEB J. 2006;20(6):661-9.
xxxi. Wicksell RK, Kihlgren M, Melin L, Eeg-Olofsson O. Specific cognitive deficits are common in children with Duchenne muscular dystrophy. Dev Med Child Neurol. 2004;46(3):154-9.
xxxii. Moizard MP, Toutain A, Fournier D, Berret F, Raynaud M, Billard C, Andres C, Moraine C. Severe cognitive impairment in DMD: obvious clinical indication for Dp71 isoform point mutation screening. Eur J Hum Genet. 2000;8(7):552-6.
xxxiii. Walko G, Wögenstein KL, Winter L, Fischer I, Feltri ML, Wiche G. Stabilization of the dystroglycan complex in Cajal bands of myelinating Schwann cells through plectin-mediated anchorage to vimentin filaments. Glia. 2013;61(8):1274-87.
xxxiv. Masaki T, Matsumura K. Biological role of dystroglycan in Schwann cell function and its implications in peripheral nervous system diseases. J Biomed Biotechnol. 2010;2010:740403.
xxxv. Chopp M, Li Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol. 2002;1(2):92-100.
xxxvi. Sasaki M, Radtke C, Tan AM, Zhao P, Hamada H, Houkin K, Honmou O, Kocsis JD. BDNF-hypersecreting human mesenchymal stem cells promote functional recovery, axonal sprouting, and protection of corticospinal neurons after spinal cord injury. J Neurosci. 2009;29(47):14932-41.
xxxvii. Miyan JA, Zendah M, Mashayekhi F, Owen-Lynch PJ. Cerebrospinal fluid supports viability and proliferation of cortical cells in vitro, mirroring in vivo development. Cerebrospinal Fluid Res. 2006;3:2.
xxxviii. Mashayekhi F, Salehi Z. The importance of cerebrospinal fluid on neural cell proliferation in developing chick cerebral cortex. Eur J Neurol. 2006;13(3):266-72.
xxxix. Sveen ML, Jeppesen TD, Hauerslev S, Køber L, Krag TO, Vissing J. Endurance training improves fitness and strength in patients with Becker muscular dystrophy. Brain. 2008;131(Pt 11):2824-31.
xl. Roque JM, Carvalho VO, Pascoalino LN, Ferreira SA, Bocchi EA, Guimarães GV. Physical training in Becker muscular dystrophy associated with heart failure. Arq Bras Cardiol. 2011;97(6):e128-31.
xli. Sveen ML, Andersen SP, Ingelsrud LH, Blichter S, Olsen NE, Jønck S, Krag TO, Vissing J. Resistance training in patients with limb-girdle and becker muscular dystrophies. Muscle Nerve. 2013;47(2):163-9.
xlii.DiMarco AF, Kelling JS, DiMarco MS, Jacobs I, Shields R, Altose MD. The effects of inspiratory resistive training on respiratory muscle function in patients with muscular dystrophy. Muscle Nerve. 1985;8(4):284-90.
xliii. Wanke T, Toifl K, Merkle M, Formanek D, Lahrmann H, Zwick H. Inspiratory muscle training in patients with Duchenne muscular dystrophy. Chest. 1994;105(2):475-82.
xliv. Ridall L, Gralla J, Mourani PM, Czaja A, Yang M, Cunniff C, Donnelly JA, Ciafaloni E, Oleszek J, Pandya S, Price E, Auerbach S. Progression of left ventricular dysfunction in childhood-onset Duchenne and Becker muscular dystrophies. J Am Coll Cardiol. 2014;63(12_S).
xlv.Lu, Yen-Mou, and Yi-Jing Lue. Strength and Functional Measurement for Patients with Muscular Dystrophy. INTECH Open Access Publisher, 2012.
xlvi. Ricotti V, Ridout DA, Pane M, Main M, Mayhew A, Mercuri E, Manzur AY, Muntoni F; on behalf of UK NorthStar Clinical Network. The NorthStar Ambulatory Assessment in Duchenne muscular dystrophy: considerations for the design of clinical trials. J Neurol Neurosurg Psychiatry. 2015. pii: jnnp-2014-309405.
xlvii. Finanger EL, Russman B, Forbes SC, Rooney WD, Walter GA, Vandenborne K. Use of skeletal muscle MRI in diagnosis and monitoring disease progression in Duchenne muscular dystrophy. Phys Med Rehabil Clin N Am. 2012;23(1):1-10, ix.
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