Survival motor neuron protein is the optimal biomarker for evaluating the risdiplam treatment.

BACKGROUND

The clinical use of three disease-modifying drugs approved in Japan for the treatment of spinal muscle atrophy (SMA) has increased. Therefore, there is an increasing need for biomarkers to evaluate therapeutic interventions.

METHODS

Individuals were treated with risdiplam (25 patients, male:female =12:13) and evaluated before starting the medication and after 1, 2, 5, 8, and 12 months. Assessments included the Hammersmith Functional Motor Scale Expanded (HFMSE), Revised Upper Limb Module (RULM), compound muscle action potential (CMAP) of the ulnar and peroneal nerves, and spinal muscular atrophy independence scale upper limb module (SMAIS-ULM) questionnaire scores of the patient and caregiver. Blood tests and survival motor neuron (SMN) protein levels were also evaluated.

RESULTS

The HFMSE and RULM scores increased significantly at 5 (p = 0.058 and p = 0.003, respectively), 8 (p = 0.024 and p = 0.016, respectively), and 12 months (p = 0.034 and p = 0.046, respectively). Peroneal CMAP scores also increased at eight months (p = 0.038) compared with those before treatment initiation. SMN protein levels were elevated after one month of treatment (p = 0.001) and were maintained throughout the observation period.

CONCLUSIONS

Median SMN protein levels increased significantly after one month of risdiplam administration with some fluctuations. After five months of treatment, motor function, CMAP, and SMAIS-ULM caregiver scores improved. SMN protein is an appropriate biomarker for monitoring and evaluating the efficacy of risdiplam treatment in SMA.