Combined therapy of valproic acid and an SMN2 splicing modifier for an adult patient with SMA type II

Abstract

Background

Spinal muscular atrophy (SMA) is a lower motor neuron disease caused by Survival of Motor Neuron 1 gene (SMN1) deletions or other mutations. SMA is characterized by the progressive deterioration of motor and respiratory functions. New drugs that increase the gene product (SMN protein) levels, such as nusinersen, onasemnogene abeparvovec, and risdiplam, have been reported to ameliorate the symptoms and improve the prognosis of infants with SMA. Among these, nusinersen and risdiplam are SMN2 splicing modifiers suitable for patients of all ages. However, these drugs have limited efficacy in older children and adults with SMA. Therefore, there is a need for more effective therapies for these patients.

Case presentation

Here, we report an adult patient with SMA type II. The patient was treated with valproic acid (VPA, a histone deacetylase inhibitor) and an SMN2 splicing modifier, risdiplam. With the combined therapy of VPA and risdiplam over a period of more than 2 years, the patient’s clinical course was uneventful, without requiring hospitalization for acute illness such as pneumonia. In addition, motor function in the upper extremities improved during this period.

Conclusion

Combined treatment with VPA and risdiplam resulted in a stable disease course in our adult SMA patient. Thus, combined therapy consisting of drugs with different mechanisms of action might be effective for adult SMA.