Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. Risdiplam treatment increased the survival of motor neuron protein in the blood of infant patients diagnosed with type 1 spinal muscular atrophy.

2. Treatment with risdiplam resulted in adverse events such as respiratory tract infections, pneumonia, and acute respiratory failure.

Evidence Rating Level: 2 (Good)

Study Rundown:

Type 1 spinal muscular atrophy is an autosomal recessive disease that results from a deletion or mutation in chromosome 5q. This disease leads to a decreased survival of motor neuron (SMN) protein leading to the inability to sit without support and reduce life expectancy. This study examined the safety and efficacy of risdiplam, which is an SMN2 pre-messenger RNA splicing modifier that increases the SMN blood level. Study participants were enrolled into two cohorts and further assessed via physical examinations, vital signs, and electrocardiography. The baseline survey revealed no infants were able to sit without support; however, at the end of the study, seven infants from the high-dose cohort were able to sit for at least 5 seconds with no support. Moreover, the laboratory blood test results revealed an increase in the expression of the SMN protein. The study was limited by a small cohort size. Nonetheless, the results are significant, as the study determined a potential pharmacological treatment to reduce the musculoskeletal effects of type 1 spinal muscular atrophy.

In-Depth [prospective cohort]:

This open-label study enrolled 21 pediatric patients into either a low-dose risdiplam (0.08 mg per kilogram of body weight) or high-dose risdiplam (0.2 mg per kilogram of body weight) cohort. In order to be eligible, the infants must have been between one and seven months of age with confirmed Type 1 spinal muscular atrophy and two copies of SMN2. Those that had previously received SMN2-targeting treatment for this condition were excluded from the study. Risdiplam was administered once a day in patients by means of oral liquid form or through a bolus via a feeding tube. The primary outcome was treatment safety, as well as pharmacokinetics and pharmacodynamics of risdiplam. The low-dose cohort had a blood concentration of SMN protein of 1.31 ng per milliliter at baseline and 3.05 ng per milliliter at 12 months. The high-dose cohort revealed blood levels of 2.54 ng per milliliter at baseline and 5.66 ng per milliliter at 12 months. At one-year follow-up, 90% of the infants reported no clinical events. However, adverse events were noted including pneumonia, infection of the respiratory tract, and also acute respiratory failure. Death was reported for four infants at the time of article publication. A higher dose of risdiplam has been selected to be investigated further. As such, the study determined risdiplam to be a viable therapeutic option to treat type 1 spinal muscular atrophy.

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