摘要：Spinal muscular atrophy (SMA) is the most frequent genetic cause of death in infants and toddlers. All casesof spinal muscular atrophy result from reductions in levels of the survival motor neuron (SMN) protein,and so SMN upregulation is a focus of many preclinical and clinical studies. We examine four issues thatmay be important in planning for therapeutic success. First, neuromuscular phenotypes in the SMNΔ7mousemodel closelymatch those in human patients but peripheral disease manifestations differ, suggestingthat endpoints other than mouse lifespan may be more useful in predicting clinical outcome. Second, SMNplays important roles in multiple central and peripheral cell types, not just motor neurons, and it remainsunclear which of these cell types need to be targeted therapeutically. Third, should SMN-restorationtherapy not be effective in all patients, blocking molecular changes downstream of SMN reduction mayconfer significant benefit, making it important to evaluate therapeutic targets other than SMN. Lastly, forpatients whose disease progression is slowed, but who retain significant motor dysfunction, additionalapproaches used to enhance regeneration of the neuromuscular system may be of value.
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