Spinal muscular atrophy: development and implementation of potential treatments.
In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.
Neuromuscular Division, Department of Neurology, Wexner Medical Center, the Ohio State University, Columbus, OH; Department of Physical Medicine and Rehabilitation, Wexner Medical Center, the Ohio State University, Columbus, OH.
W David
WD
Arnold
Arthur H M
AH
Burghes
D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009134:Muscular Atrophy, Spinal / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D055533:Survival of Motor Neuron 1 Protein / Q000235:genetics* / Q000378:metabolism
D055533:Survival of Motor Neuron 1 Protein