Research Journal of Pharmacology and Pharmacodynamics

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Review on Spinal Muscular Atrophy


Affiliations
1 AISSMS College of Pharmacy, Pune, India
     

   Subscribe/Renew Journal


Spinal muscular atrophy (SMA) is the second leading genetic, autosomal recessive disorder with progressive weakness of skeletal and respiratory muscles, leading to progressive paralysis with muscular atrophy, significant disability. SMA predominantly affects on children and represents the most common cause of hereditary infant mortality. Spinal muscular atrophy caused by mutations in the survival motor neuron 1 (SMN1) gene and a consequentdecrease in the SMN protein leading to lower motor neuron degeneration. The clinical features of Spinal muscular atrophy are caused by specific degeneration of a-motor neurons in the spinal cord, leading to muscle weakness, atrophy and, in the majority of cases, premature death. Encouraging results from phase II and III clinical trials have raised hope that other therapeutic options will enter soon in clinical practice. The common genetic etiology and recent progress in pre-clinical models suggest that SMA is well-suited for the development of therapeutic regimens. This review covers the available data and the new challenges of SMA therapeutic strategies.

Keywords

Spinal muscular atrophy, Clinical Features, Therapy.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Messina S, Sframeli M. New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges. Journal of Clinical Medicine. 2020;9(7):2222.

  • Lefebvre S, Bürglen L, Reboullet S. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995;80(1):155-165.

  • Farrar M, Vucic S, Johnston H, du Sart D. Pathophysiological Insights Derived by Natural History and Motor Function of Spinal Muscular Atrophy. The Journal of Pediatrics. 2013;162(1):155- 159.

  • Groen E, Talbot K, Gillingwater T. Advances in therapy for spinal muscular atrophy: promises and challenges. Nature Reviews Neurology. 2018;14(4):214-224.

  • Lorson C, Rindt H, Shababi M. Spinal muscular atrophy: mechanisms and therapeutic strategies. Human Molecular Genetics. 2010;19(R1):R111-R118.

  • Wang C, Finkel R, Bertini E, Schroth M. Consensus Statement for Standard of Care in Spinal Muscular Atrophy. Journal of Child Neurology. 2007;22(8):1027-1049.

  • Darras B, Kang P. Clinical trials in spinal muscular atrophy. Current Opinion in Pediatrics. 2007;19(6):675-679.

  • Oskoui M, Levy G, Garland C, Gray J. The changing natural history of spinal muscular atrophy type 1. Neurology. 2007;69(20):1931-1936.

  • Swoboda K. Natural history of denervation in SMA: Relation to age,SMN2 copy number, and function. Annals of Neurology. 2005;57(5):704-712.

  • Munsat T, Davies K. International SMA Consortium Meeting (26– 28 June 1992, Bonn, Germany). Neuromuscular Disorders. 1992;2(5-6):423-428.

  • Dubowitz V. Very severe spinal muscular atrophy (SMA type 0): an expanding clinical phenotype. European Journal of Paediatric Neurology. 1999;3(2):49-51.

  • Mercuri E, Bertini E, Iannaccone S. Childhood spinal muscular atrophy: controversies and challenges. The Lancet Neurology. 2012;11(5):443-452.

  • Arnold W, Kassar D, Kissel J. Spinal muscular atrophy: Diagnosis and management in a new therapeutic era. Muscle and Nerve. 2014;51(2):157-167.

  • Macleod M, Taylor J, Lunt P, Mathew C, Robb S. Prenatal onset spinal muscular atrophy. European Journal of Paediatric Neurology. 1999;3(2):65-72.

  • Finkel RS, et al. Observational study of spinal muscular atrophy type I and implications for clinical trials. Neurology. 2014;83(9):810–817.

  • Zerres K, Rudnik-Schoneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995;52(5):518–523.

  • Schmalbruch H, Haase G. Spinal Muscular Atrophy: Present State. Brain Pathology. 2006;11(2):231-247.

  • Shababi M, Habibi J, Yang H, Vale S. Cardiac defects contribute to the pathology of spinal muscular atrophy models. Human Molecular Genetics. 2010;19(20):4059-4071.

  • von Gontard A, Zerres K, Backes M. Intelligence and cognitive function in children and adolescents with spinal muscular atrophy. 2021.

  • Messina S, Pane M. Feeding problems and malnutrition in spinal muscular atrophy type II. Neuromuscular Disorders. 2008;18(5):389-393.

  • Zerres K, Rudnik-Schöneborn S, Forrest E, Lusakowska A. A collaborative study on the natural history of childhood and juvenile onset proximal spinal muscular atrophy (type II and III SMA): 569 patients. Journal of the Neurological Sciences. 1997;146(1):67-72.

  • Piepers S, Berg L, Brugman F, Scheffer H. A natural history study of late onset spinal muscular atrophy types 3b and 4. Journal of Neurology. 2008;255(9):1400-1404.

  • Mahadevan, M. S, Korneluk, R. G, and Roy, N. MacKenzie, A., and Ikeda, J. (1995). SMA genes: deleted and duplicated. Nat. Genet. , 9, 112-113.

  • Lorson C, Hahnen E, Androphy E, Wirth B. A single nucleotide in the SMN gene regulates splicing and is responsible for spinal muscular atrophy. Proceedings of the National Academy of Sciences. 1999;96(11):6307-6311.

  • Monani U. A single nucleotide difference that alters splicing patterns distinguishes the SMA gene SMN1 from the copy gene SMN2. Human Molecular Genetics. 1999;8(7):1177-1183.

  • Simic G. Pathogenesis of proximal autosomal recessive spinal muscular atrophy. ActaNeuropathologica. 2008;116(3):223-234.

  • Baioni M, Ambiel C. Spinal muscular atrophy: diagnosis, treatment and future prospects. Jornal de Pediatria. 2010;86(4):261-270.

  • Gitler A, Dhillon P, Shorter J. Neurodegenerative disease: models, mechanisms, and a new hope. Disease Models and Mechanisms. 2017;10(5):499-502.

  • Hassan H, Zaki M, Issa M, El-Bagoury N, Essawi M. Genetic pattern of SMN1, SMN2, and NAIP genes in prognosis of SMA patients. Egyptian Journal of Medical Human Genetics. 2020;21(1).

  • Nadkarni J, Dastur R, Gaitonde P, Khadilkar S, Udani V. Correlation between deletion patterns of SMN and NAIP genes and the clinical features of spinal muscular atrophy in Indian patients. Neurology India.

  • McAndrew P, Parsons D, Simard L, Rochette C, Ray P. Identification of Proximal Spinal Muscular Atrophy Carriers and Patients by Analysis of SMNT and SMNC Gene Copy Number. The American Journal of Human Genetics. 1997;60(6):1411-1422.

  • Mohseni J, Zabidi-Hussin Z, Sasongko T. Histone deacetylase inhibitors as potential treatment for spinal muscular atrophy. Genetics and Molecular Biology. 2013;36(3):299-307.

  • Brichta L. Valproic acid increases the SMN2 protein level: a wellknown drug as a potential therapy for spinal muscular atrophy. Human Molecular Genetics. 2003;12(19):2481-2489.

  • Chang J, Hsieh-Li H, Jong Y, Wang N. Treatment of spinal muscular atrophy by sodium butyrate. Proceedings of the National Academy of Sciences. 2001;98(17):9808-9813.

  • Mercuri E, Bertini E, Messina S, Solari A. Randomized, doubleblind, placebo-controlled trial of phenylbutyrate in spinal muscular atrophy. Neurology. 2006;68(1):51-55.

  • Riessland M, Ackermann B, Förster A, Jakubik M, Hauke J. SAHA ameliorates the SMA phenotype in two mouse models for spinal muscular atrophy. Human Molecular Genetics. 2010;19(8):1492-1506.

  • Garbes L, Riessland M, Hölker I, Heller R. LBH589 induces up to 10-fold SMN protein levels by several independent mechanisms and is effective even in cells from SMA patients non-responsive to valproate. Human Molecular Genetics. 2009;18(19):3645-3658.

  • Powe C, Allen M, Puopolo K, Merewood A. Recombinant human prolactin for the treatment of lactation insufficiency. Clinical Endocrinology. 2010;73(5):645-653.

  • Andreassi C. Aclarubicin treatment restores SMN levels to cells derived from type I spinal muscular atrophy patients. Human Molecular Genetics. 2001;10(24):2841-2849.

  • Lim S, Hertel K. Modulation of Survival Motor Neuron PremRNA Splicing by Inhibition of Alternative 3′ Splice Site Pairing. Journal of Biological Chemistry. 2001;276(48):45476-45483.

  • Singh N, Shishimorova M, Cao L, Gangwani L, Singh R. A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy. RNA Biology. 2009;6(3):341-350.

  • Williams J, Schray R, Patterson C, Ayitey S, Tallent M, Lutz G. Oligonucleotide-Mediated Survival of Motor Neuron Protein Expression in CNS Improves Phenotype in a Mouse Model of Spinal Muscular Atrophy. Journal of Neuroscience. 2009;29(24):7633-7638.

  • Wolstencroft E. A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels. Human Molecular Genetics. 2005;14(9):1199-1210.

  • Mattis V, Rai R, Wang J, Chang C, Coady T, Lorson C. Novel aminoglycosides increase SMN levels in spinal muscular atrophy fibroblasts. Human Genetics. 2006;120(4):589-601.

  • Mastri M. Enhancing the efficacy of mesenchymal stem cell therapy. World Journal of Stem Cells. 2014;6(2):82.

  • Passini, M. and Bu, J., 2010. CNS-targeted gene therapy improves survival and motor function ina mouse model of spinal muscular atrophy. Journal of Clinical Investigation, 120(4), pp.1253-1264.

  • Valori, C. and Ning, K., 2010. Systemic Delivery of scAAV9 Expressing SMN Prolongs Survival in a Model of Spinal Muscular Atrophy. ScienceTranslational Medicine, 2(35).

  • PM.Patil, PD Chaudhari, MeghaSahu , NJ Duragkar. Review Article on Gene Therapy. Research J. Pharmacology and Pharmacodynamics. 2012; 4(2): 77-83.

  • Tsai, L., 2012. Therapy Development for Spinal Muscular Atrophy in SMN Independent Targets. Neural Plasticity, 2012, pp.1-13.

  • Joseph V, Joseph. J.Effectiveness of aromatherapy and quality of sleep among elderly inmates of selected old age home. Asian J. Nur. Edu. and Research.2016; 6(4): 511-516.

  • Jose B, Thomas ST, Sr. Sajeena. Effectiveness of yoga therapy on stress and concentration among students of selected schools in Kerala. Asian J. Nur. Edu. and Research.2017; 7(3): 299-304.

  • Khan MY, Roy M, Saroj BK, Dubey S.A Review- Benefits of Panchgavya therapy (Cowpathy) for health of humans. Asian J. Res. Pharm. Sci. 5(2): 2015; 115-125.

  • Manjusha P. Yeole, Shailju G. Gurunani, Seema M. Dhole, Yogesh N. Gholse. Muscular Dystrophy. Research J. Pharm. and Tech. 7(5): May, 2014; Page 618-620.

  • R. Nalini. Effect of Music therapy on pain among Post-operative patients at selected Hospital. International Journal of Advances in Nursing Management. 2021; 9(3):309-4. 1. (Music therapy on SMA). 2. 55. T. Sasikala, S. Kamala. Therapeutic Effects of Music Therapy on Preterm Neonates – Pilot Study Report. Int. J. Nur. Edu. and Research 4(1): Jan.-Mar., 2016; Page 42-44.

  • J. Annalakshmi, T. Sivabalan. Effectiveness of Progressive Muscle Relaxation therapy (PMR) on Health Status among Cancer Patients Receiving Chemotherapy Treatment. Int. J. Nur. Edu. and Research. 2017; 5(1): 47-50.

  • Omkar A. Devade, Rohan D. Londhe, Nisarga V. Sokate, Utkarsha R. Randave, Pallavi A. Ranpise. A Review on: Polycystic Ovarian Disorder. Asian Journal of Research in Pharmaceutical Sciences. 2022; 12(3):219-6. 10.52711/2231-5659.2022.00039

  • Sinha K, Lohith B, Ashvini M. Abhyanga: Different contemporary massage technique and its importance in Ayurveda. Journal of Ayurveda and Integrated Medical Sciences (JAIMS). 2017;2(3).

  • M K, N K. Case Study on Ayurvedic Management of Spinal Muscular Atrophy (SMA). International Journal of Ayurvedic Medicine. 2018;9(3):225-230.

  • K. Priscilla, NaliniJayavanthSantha, K. Priscilla. Massage Therapy- Complementary and Alternative Therapeutic approach. Asian J. Nur. Edu. and Research 4(4): Oct.- Dec., 2014; Page 516- 519.


Abstract Views: 345

PDF Views: 0




  • Review on Spinal Muscular Atrophy

Abstract Views: 345  |  PDF Views: 0

Authors

Omkar A. Devade
AISSMS College of Pharmacy, Pune, India
Rohan D. Londhe
AISSMS College of Pharmacy, Pune, India
Nikhil M. Meshram
AISSMS College of Pharmacy, Pune, India

Abstract


Spinal muscular atrophy (SMA) is the second leading genetic, autosomal recessive disorder with progressive weakness of skeletal and respiratory muscles, leading to progressive paralysis with muscular atrophy, significant disability. SMA predominantly affects on children and represents the most common cause of hereditary infant mortality. Spinal muscular atrophy caused by mutations in the survival motor neuron 1 (SMN1) gene and a consequentdecrease in the SMN protein leading to lower motor neuron degeneration. The clinical features of Spinal muscular atrophy are caused by specific degeneration of a-motor neurons in the spinal cord, leading to muscle weakness, atrophy and, in the majority of cases, premature death. Encouraging results from phase II and III clinical trials have raised hope that other therapeutic options will enter soon in clinical practice. The common genetic etiology and recent progress in pre-clinical models suggest that SMA is well-suited for the development of therapeutic regimens. This review covers the available data and the new challenges of SMA therapeutic strategies.

Keywords


Spinal muscular atrophy, Clinical Features, Therapy.

References