Vamshi Rao, MD, attending physician of Neurology at Ann and Robert H. Lurie Children’s Hospital of Chicago, discusses how disease modifying therapies have improved spinal muscular atrophy (SMA) prognosis.
Vamshi Rao, MD, is an attending physician of Neurology at Ann and Robert H. Lurie Children’s Hospital of Chicago and assistant professor of Pediatrics (Neurology and Epilepsy) at Northwestern University Feinberg School of Medicine.
What does a “good prognosis” look like in SMA, now that there is a disease- modifying therapy?
Rao: The prognosis is definitely better than what we anticipated when the disease-modifying therapies were not out there. It still depends on the type of SMA that we're looking at. There are 3 types of SMA and the one that is most severe is the type 1, where kids used to not survive beyond the age of 18 months and they never achieved the ability to even sit up.
I think the greatest difference these drugs have made is in type 1 SMA because the endpoints of the clinical trials were either death or permanent ventilation. If you look at that as a prognosis, we are definitely way beyond that. We don't have deaths occurring because of SMA type 1 and as far as the need for permanent ventilation, that has also decreased with a very important caveat, which is, when do you treat these children with the disease-modifying therapies. As we found out in the clinical trials, the earlier the treatment, the better the prognosis. So, the pivotal clinical trials for SMA type 1 showed that these kids [children treated under 6 months of age] not only stabilized but also achieved more motor milestones, which they had never done before.
As far as treating them even prior to when we think is the time that the motor neurons die, somewhere around 4 to 6 weeks of age, these kids do very well. In fact, we have some children that have been treated after the drugs were approved, the real world or commercial data, where the children actually don't look much different from children without SMA. So, that is a very, very phenomenal prognostic benchmark for us—these kids are sitting up, some of them are crawling, and there are a few kids that are walking. And these are kids that were never supposed to be alive after 18 months of age.
So, to answer your question, in terms of prognosis, it's very different for type 1, type 2, and type 3. Kids with SMA type 2 were kids who were going to sit up but would never achieve the ability to walk. Kids, young adults, and adults with type 3 were individuals who would walk but could become nonambulatory over time. There's still a lot of clinical trials that are being done to assess that and a lot of data that is coming out from the real world as to what exactly the prognosis is going to look like for type 2 and type 3. But it does look like that there's an improvement. The question is how far, how sustained, and how long?