Karen Chen, PhD, Chief Executive Officer of the Spinal Muscular Atrophy (SMA) Foundation, discusses how the treatment landscape for SMA has changed in the last 5 years.
Spinal muscular atrophy (SMA) is a rare inherited neuromuscular disorder caused by an inadequate level of the survivor motor neuron (SMN) protein due to mutations in the SMN1 gene. The absence of the SMN protein leads to cellular imbalances in motor neurons that in turn causes the motor neuron endplates to not properly connect to muscle and the motor neurons die.
As Dr. Chen explains, in December 2016 nusinersen (Spinraza) was approved as the first drug approved to treat SMA. However, at the time this drug was administered through intrathecal injection. Nusinersen is an antisense oligonucleotide that works on a second, relatively silent gene, SMN2, to increase the amount of SMN protein that’s available in the body.
Dr. Chen then notes that in May 2019, the first gene therapy – onasemnogene abeparvovec-xioi (Zolgensma) – was approved to treat SMA. This gene therapy delivers a fully functional copy of the SMN1 gene into the target motor neuron cells in SMA patients.
In August 2020, the third and most recent SMA treatment approved was risdiplam (Evrysdi). Risdiplam was the first oral treatment approved for SMA and works by modifying the splicing of SMN2 messenger RNA to include exon 7, resulting in an increase in the concentration of the functional SMN protein.
In closing, Dr. Chen notes that, now that SMA patients have a few options to reduce musculoskeletal damage, research in SMA is now focusing on developing treatments that reverse musculoskeletal damage.
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