John Brandsema, MD: Once somebody knows that they have SMA [spinal muscular atrophy], then they should establish care with an SMA care center as soon as possible. This is really evolving in 2020, when I’m speaking to you, because newborn screening is coming into play across the United States. Many babies are being identified as being genetically affected with SMA before they have any symptoms with the disease, which means that this is a very exciting time.
We also have the ability to diagnose a fetus with SMA if their parents are also carrier tested during the pregnancy. If both parents test positive as carriers of an SMN1 mutation, which is usually a deletion, we can test the fetus and determine that they are in fact affected by SMA before they’re even born.
The concept is to get to care as soon as possible because we know that, even without any other considerations of treatment, optimizing interdisciplinary support for these patients improves outcomes. When you look at the life expectancy for people living with infantile onset SMA in the 1980s and 1990s vs new advances in things like pulmonary support and nutrition support, we have extended the life span of patients living in the natural history with SMA by decades in some cases with good quality of life because of this augmentation in their supportive care.
Since 2016, we have had a major shift in our SMA care with the emergence of targeted therapies. We now have 3 FDA-approved therapies for this disease in the context of nusinersen, risdiplam, and onasemnogene abeparvovec or gene transfer for SMA. All 3 of these treatments work to correct the genetic deficiency in SMA by increasing the amount of survival motor neuron, or SMN protein, that a patient has when they’re deficient due to their genetic issue.
The challenge in this disease in terms of treatment is that it’s not like epilepsy, where if you put somebody on antiseizure medication, then they stop having seizures and you have a good outcome. What’s happening in this disease is that motor neurons are dying. Once a motor neuron is gone, it does not come back. We don’t have the ability to make more motor neurons with our body. We have the population that we’re going to have for life when we’re born.
Stabilizing motor neurons with these interventions, whether it’s any of the 3 available treatments, SMA treatment needs to be done as soon as possible for anybody living with SMA. They need to get these motor neurons healthy and stabilized so that they’re not lost, because once a motor neuron disappears, all the body can do is reinnervate from the motor neurons that are left. If those motor neurons are also sick, all you’re going to see is worse and worse weakness over time and a poor outcome.
If we get somebody on treatment, then we’re able to stabilize their motor neurons and keep them either the same for long periods of time, or if you catch them early in development, sometimes even normal development can improve a patient at first in terms of their function before they start to plateau and stay stable for a longer period of time.
Even if we’re able to slow down the rate at which things are getting worse in this disease, by just having the trajectory being less steep in terms of the loss, that is a therapeutic effect that warrants treatment in a disease that is as severe and impactful as SMA is in terms of neurodegeneration. The basic message is time is motor neuron, just as time is brain and stroke. We need to get people on treatment as soon as possible once they’re identified with this genetic disease.
Consultant: Alexion, Audentes, AveXis, Biogen, Cytokinetics, Genentech, Momenta, NS Pharma, PTC Therapeutics, Sarepta, Scholar Rock, WaVE
Research support: Alexion, Astellas, AveXis, Biogen, CSL Behring, Cytokinetics, Fibrogen, Genentech, Pfizer, PTC Therapeutics, Sarepta, Summit, WaVE
Speaker: AveXis and Biogen