Spinal Muscular atrophy therapeutics development in SMA: Difference between revisions
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[[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''' (Lunke 2009, Sumner 2006, Chang 2001). | |||
*'''Phenylbutyrate''' | |||
*'''Valproic acid''' - already widely used in treatment of [[Epilepsy]] | |||
*'''LBH589 (hydroxamic acid)''', already widely used in [[cancer]] clinical trials | |||
Drugs that are not histone deacetylase inhibitors, but that also affect SMN2 gene expression levels or promote inclusion of exon 7 are- | |||
*'''Albuterol''', a [[beta-adrenergic agonist]] already widely used in treatment of [[Asthma]]. | |||
*'''Indoprofen''' is a [[Non-steroidal anti-inflammatory]] drug. | |||
''Other approaches''- | |||
*'''Aminoglycosides''' appear to promote read-through of the [[stop codon]] and thereby stabilize the [[SMN]] protein (Wolstencraft 2005). | |||
*'''[[Riluzole]] and [[Gabapentin]]''' (Haddad 2003). | |||
*'''[[NMDA receptor activation]]''' (Biondi, 2010). | |||
*'''[[Antisense oligonucleotides]]''' ([[ASO]]) have been shown to prevent skipping of [[exon]] 7, that in turn enhances production of full-length SMN [[mRNA]] in [[fibroblasts]] from patients (Singh et al. 2009 | |||
*'''[[Stem cells therapy]]''' - [[Pluripotent]] stem cells with the capacity to differentiate into motor neurons could serve as an important model system (Ebert 2009). | |||
*'''[[Gene therapy]]''' (Foust 2010) | |||
Revision as of 18:29, 24 June 2011
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
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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' (Lunke 2009, Sumner 2006, Chang 2001).
- Phenylbutyrate
- Valproic acid - already widely used in treatment of Epilepsy
- LBH589 (hydroxamic acid), already widely used in cancer clinical trials
Drugs that are not histone deacetylase inhibitors, but that also affect SMN2 gene expression levels or promote inclusion of exon 7 are-
- Albuterol, a beta-adrenergic agonist already widely used in treatment of Asthma.
- Indoprofen is a Non-steroidal anti-inflammatory drug.
Other approaches-
- Aminoglycosides appear to promote read-through of the stop codon and thereby stabilize the SMN protein (Wolstencraft 2005).
- Riluzole and Gabapentin (Haddad 2003).
- NMDA receptor activation (Biondi, 2010).
- Antisense oligonucleotides (ASO) have been shown to prevent skipping of exon 7, that in turn enhances production of full-length SMN mRNA in fibroblasts from patients (Singh et al. 2009
- Stem cells therapy - Pluripotent stem cells with the capacity to differentiate into motor neurons could serve as an important model system (Ebert 2009).
- Gene therapy (Foust 2010)