John Brandsema, MD: One of the first questions that arises when talking about adults living with SMA [spinal muscular atrophy] is that most people have a concept of this disease as being pediatric onset. This is true in the vast majority of cases. Most people will already be experiencing symptoms of their SMA from the beginning of life if they have the most severe form, or at the latest in late childhood or teenager-hood in the least severe form of pediatric-onset SMA.
There is a very rare form in less than 2% of SMA patients that presents exclusively in adulthood, classified as type 4, in which patients will have been entirely healthy until after their 18th birthday. At that point they may experience symptoms of progressive weakness.
The point is that the disease, while it can be quite rapid at the beginning for the most severely affected patients, by the time people reach the age of adulthood, they are much more slowly progressive in their relentless loss of strength with this disease. Rather than noticing a difference week to week or even month to month, it sometimes takes years before a significant difference in function is appreciable by the patient.
When we’re talking to an adult living with SMA in the clinic, we often ask, “Is anything different from your last visit 6 months or a year ago?” They’ll often say, “No.” So it really has to be a reflection on 5 years ago or 10 years ago with regard to the things that the patient was able to do then that they can’t do now. Most people can then reflect and bring those things forward. That slow rate of change does make trying to understand a therapeutic response to a new treatment in SMA much more challenging because the effect of the disease itself is slow in its change. Unless the treatment had a very big impact on someone’s baseline level of function, and they noticed it right away, understanding that there’s a difference from the natural history of progressive loss takes much more time.
Another important point to consider when dealing with adults with SMA is that they should have a genetic confirmation of their disease. By far, the majority of patients with SMA have a double deletion of the SMN1 gene. About 3% or 4% will have a sequence change or some other genetic mutation in SMN1 that is leading to it being unfunctional on 1 of the alleles.
If your patient does not have classically defined 5q SMA through genetic testing, it is not appropriate to offer them targeted therapies that are now available for SMA. They should really have further testing such as EMG [electromyogram] and possibly other broader genetic panels to try to understand why they have the symptoms of weakness that they do.
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