Spinal muscular atrophy therapeutics development

Jump to navigation Jump to search

Spinal Muscular Atrophy Microchapters

Home

Patient Info

Overview

Epidemiology and Demographics

Risk Factors

Screening

Other forms

Molecular Biology

Genetics

Types

Diagnosis

Diagnosis

Full Differential Diagnosis

Symptom

Physical Examination

Electrolyte & Biomarker Studies

Electrocardiogram

Chest X Ray

MRI and CT

Echocardiography or Ultrasound

Other Imaging Findings

Pathology

Other Diagnostic Studies

Treatment

Outcome measures

Therapeutics development

Indications For Surgery

Research

Pre-Operative Assessment

Post-Operative Assessment

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Spinal muscular atrophy therapeutics development Resources

Most recent articles on Spinal muscular atrophy therapeutics development

Most cited articles on Spinal muscular atrophy therapeutics development

Review articles on Spinal muscular atrophy therapeutics development

Review articles on Spinal muscular atrophy therapeutics development

CME Programs on Spinal muscular atrophy therapeutics development

Powerpoint slides on Spinal muscular atrophy therapeutics development

Images of Spinal muscular atrophy therapeutics development

Ongoing Trials on Spinal muscular atrophy therapeutics development at Clinical Trials.gov

US National Guidelines Clearinghouse on Spinal muscular atrophy therapeutics development

NICE Guidance on Spinal muscular atrophy therapeutics development

FDA on Spinal muscular atrophy therapeutics development

CDC on Spinal muscular atrophy therapeutics development

Spinal muscular atrophy therapeutics development in the news

Blogs on Spinal muscular atrophy therapeutics development

Directions to Hospitals Treating Spinal muscular atrophy therapeutics development

Risk calculators and risk factors for Spinal muscular atrophy therapeutics development


Editors-in-Chief: C. Michael Gibson, M.S., M.D.; Priyamvada Singh, MBBS

Overview

SMA disease severity has been found to be inversely related to the number of SMN2 gene and the amount of SMN protein present. Efforts are being directed to develop agents that can increase the amount of SMN2 gene and the SMN proteins. Also, other approaches like stem cell therapy, gene therapy are active areas of research. There is no standard treatment of SMA till date. However, the recent developments in molecular genetics have helped in understanding the pathogenesis of the disease and raises hope for a future treatment. Below are the drugs that have been actively studied in animal models and various clinical trials.


Drugs that act by increasing SMN protein, number of SMN2 gene, number of nuclear gems

Histone deacetylase inhibitors.

  • 'Phenylbutyrate'
  • 'Valproic acid' - already widely used in treatment of Epilepsy
  • 'LBH589 (hydroxamic acid)', already widely used in cancer clinical trials

Non-histone deacetylase inhibitors, but that also affect SMN2 gene expression levels or promote inclusion of exon 7 are-

Other approaches-

  • 'Aminoglycosides' appear to promote read-through of the stop codon and thereby stabilize the SMN protein [1].

References

  1. Wolstencroft EC, Mattis V, Bajer AA, Young PJ, Lorson CL (2005). "A non-sequence-specific requirement for SMN protein activity: the role of aminoglycosides in inducing elevated SMN protein levels". Hum Mol Genet. 14 (9): 1199–210. doi:10.1093/hmg/ddi131. PMID 15790598.
  2. Singh NN, Shishimorova M, Cao LC, Gangwani L, Singh RN (2009). "A short antisense oligonucleotide masking a unique intronic motif prevents skipping of a critical exon in spinal muscular atrophy". RNA Biol. 6 (3): 341–50. PMC 2734876. PMID 19430205.
  3. Ebert AD, Yu J, Rose FF, Mattis VB, Lorson CL, Thomson JA; et al. (2009). "Induced pluripotent stem cells from a spinal muscular atrophy patient". Nature. 457 (7227): 277–80. doi:10.1038/nature07677. PMC 2659408. PMID 19098894.
  4. Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM; et al. (2010). "Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN". Nat Biotechnol. 28 (3): 271–4. doi:10.1038/nbt.1610. PMC 2889698. PMID 20190738.

da:Spinal muskulær atrofi de:Spinale Muskelatrophie el:Νωτιαία μυϊκή ατροφία nl:Spinale Musculaire Atrofieën fi:Spinaaliset lihasatrofiat sv:Spinal muskelatrofi


Template:WikiDoc Sources