The pediatric neurologist at Johns Hopkins Medicine provided commentary on the steps needed to improve treatment optimization in SMA, and the unanswered questions regarding the key biology of the disease.
WATCH TIME: 6 minutes
"You might say that human exceptionalism is related to the fact that we have more genes, but it’s that we have more alternative splicing than any other animal. Where is alternative splicing most important? In the brain and in early development. Anything involving the treatment of babies is fraught. We have a sorted history in the Annals of Medicine on people having unreasonable enthusiasm about a therapy that’s given to babies."
The quality of life and life expectancy for individuals with spinal muscular atrophy (SMA) varies depending on the type. Infants with SMA Type 1 usually die before their second birthday, while those with Type 2 or 3 may live full lives depending on the severity of symptoms. Those who develop SMA during adulthood (Type 4) often remain active and enjoy a normal life expectancy. After years of using off-label therapies, the field had its first major breakthrough in 2016 with the approval of nusinersen (Spinraza; Biogen), a survival motor neuron (SMN)-enhancing therapy indicated for all ages of the disease.
Years later, the community was introduced to its first gene therapy onasemnogene abeparvovec-xioi (Zolgensma; Novartis), an adeno-associated virus vector administered once, and risdiplam (Evrysdi; Biogen), another SMN2 mRNA-splicing modifier. While there’s no denying these therapies have made a significant difference for the patient community, SMA is not solved, says Thomas Crawford, MD. Crawford, an expert in the field, is currently leading the NURTURE study (NCT02386553), a long-term trial assessing the effect of nusinersen in presymptomatic infants likely to develop SMA Type 1 or 2.
Crawford, a pediatric neurologist at Johns Hopkins Medicine, sat down for an interview with NeurologyLive® to discuss the progress in treating SMA, and the greater understanding for the use of available therapeutics. In contrast, he spoke on the questions that still remain with treating the condition, including knowledge of the basic underlying pathology of SMA as well as the long-term trajectory of patients on gene transfer therapy.