Work

Spinal muscular atrophy: mechanisms and therapeutic strategies

Year: 2010

Type: review

Abstract: Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder and a leading genetic cause of infantile mortality. SMA is caused by mutation or deletion of Survival Motor Neuron-1 (SMN1). The clinical features of the disease are caused by specific degeneration of alpha-motor neurons in the spinal cord, leading to muscle weakness, atrophy and, in the majority of cases, premature death. A highly homologous copy gene (SMN2) is retained in almost all SMA patients but fails to generate adequate levels of SMN protein due to its defective splicing pattern. The severity of the SMA phenotype is inversely correlated with SMN2 copy number and the level of full-length SMN protein produced by SMN2 ( approximately 10-15% compared with SMN1). The natural history of SMA has been altered over the past several decades, primarily through supportive care measures, but an effective treatment does not presently exist. However, the common genetic etiology and recent progress in pre-clinical models suggest that SMA is well-suited for the development of therapeutic regimens. We summarize recent advances in translational research that hold promise for the progression towards clinical trials.

Source: Human Molecular Genetics

DOI: 10.1093/hmg/ddq147

Authors: C. L. Lorson, H. Rindt, M. Shababi

Institution: University of Missouri

Language: English

Topic: Neurogenetic and Muscular Disorders Research

Subfield: Genetics (clinical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Institute of Neurological Disorders and Stroke, Eunice Kennedy Shriver National Institute of Child Health and Human Development