Understanding SMA Subtypes and the Impact of Treatment Advances

Tina Duong, PhD, MPT

The classification of spinal muscular atrophy (SMA) subtypes, the role of SMN2 gene copies in disease severity, and how treatment has altered the natural history of the disease were central points covered by Tina Duong, PhD, MPT, senior research scientist of neurology at Stanford Medicine, in an interview with The American Journal of Managed Care^® (AJMC^®).

In part 2 of the interview, she also discussed differences in disease progression across various age groups, the importance of long-term management strategies, and ongoing challenges such as scoliosis development and the need for improved monitoring of muscle function.

AJMC: Why is maintaining motor function critical for older patients living with SMA, and how does it impact their quality of life?

Duong: This depends on their age and goals. For younger children and infants, meeting motor milestones is typically the goal. The goals as an adult may not be based on attaining these motor milestones but may be more function-based; it really varies. We characterize SMA based on if they're a non-sitter, sitter, or walker, just because rehabilitation treatment sometimes is really based on their functional ability.

An example I always give is how small improvements in function have large impacts for those who are weaker. I have one patient who uses his finger to control his mouse in order to work at Google, and after treatment, he was able to do that longer, and he didn't need help as he did previously when he would need help because halfway through the day [before], his finger would fall off the mouse due to fatigue and weakness. Then he needed somebody to put his finger back on the mouse in order for him to continue working. Rehabilitation really depends on the patient, their goals, and what their roles are within society. We really want to help them be as independent and functional as possible with patient-centered care.

AJMC: How do older patients with SMA fare? How do their needs differ from those of infants diagnosed with the disease?

Duong: The approach is different. From a rehab perspective, for infants, we're trying to facilitate the attainment of skill sets, while in the adults, we're trying to maintain what they have. There's also more of a fatigue issue that's noted in adults than what we see in children.

So, the perspective on how we treat is different. I think part of it is not just hands-on [care], but [offering] assistive devices and things for them to be independent and functional. That's what we primarily focus on for adults.

The other thing that I find related, and unrelated, to your question is that as a PT [physical therapist], I worked in spinal cord injury and rehabilitation. The [current] model, I feel, has changed for treating adults, where we focused on maintenance to rehabilitation or regaining strength/function.

With rehabilitation, we are facilitating a mind-body connection through neuromuscular education because some of these muscles that have been dormant—patients have been too weak to activate these muscles, so as PTs, we need to show them and teach them how to make that muscle-brain connection in order for them to contract these muscles. It’s a paradigm shift for us, or, at least, it needs to be in order for us to see if we can go beyond just maintenance [towards] improvement, because even though we have treatment, muscles do not get stronger on their own. Rehabilitation and treatment together have better results.

That makes you wonder: can exercise be a complementary medicine to the current treatments available out there? Because progressive degeneration is attributed to a few things: splicing regulation, neuromuscular junction instability, mitochondrial dysfunction, and stress. We know that exercise has some neuroprotective impacts. As a PT, it's really exciting because this field has become much more needed to understand the physiological benefits of exercise now that treatment for the underlying disease has been addressed.

AJMC: What do you see as the unmet needs in the management of patients with SMA who are 2 years and older?

Duong: A loaded question depending on if they're presymptomatic or when they were treated... I think that treatment availability for infants needs to go hand in hand with newborn screening, because without newborn screening, you're treating kids who are diagnosed symptomatically, and when they're diagnosed symptomatically, you're going to have chronic impacts of disability and weakness.

So, how do we treat symptomatic patients with this new phenotype? We really, honestly, don't know what the phenotype looks like, and so we are treating symptoms. With exercise, we need to be better at providing “prescriptions” as a PT. One of the things that we do when we don't know is give really generalized prescriptions of moderate intensity exercise for both strength and cardiovascular exercise. However, most patients do not know what that means or have not been able to exercise, so education is important for patients to feel safe enough to even start exercising.

I think my PT perspective is that it needs to be prescribed similar to how medicine is prescribed. The American College of Sports Medicine uses the FITT principles: Frequency, Intensity, Type, and [Time].¹ Following these principles, we can help guide and progress exercise more effectively to provide patients with confidence to have a physically active lifestyle.

AJMC: What are your management goals for patients living with SMA?

Duong: I think that goes back to the management of infants vs adults. It's very patient-specific; it depends on your interview with the patient, and their goals as rehabilitation should be specific to the activity the patient desires to accomplish. That's where you individualize it. I think one of the things that we in our clinic try to emphasize is that when we provide treatment, we also provide a prescription for PT, OT [occupational therapy], or speech [therapy] in order for it to be complimentary so that they can get the most out of their treatment.

AJMC: Is there anything else you want to add about SMA or want audiences to know about the condition?

Duong: I think one of the things as a PT is this evolving phenotype for SMA. PTs should not feel obligated to only evaluate with the validated SMA measures. Yes, you need to do the validated measures so you can compare what we know about the natural history, but there is vast experience from other therapists, and they should use the huge outcomes toolbox that they have for measuring progression and function specific to their rehabilitation program. I highly encourage therapists to think outside the box and consider scales such as the goal attainment scale or the Canadian occupational performance measure. These are nice ways to also measure goal-oriented progression or improvement.

One of the other gaps that we need to address is fatigue. A lot of adults report fatigue as a debilitating symptom. However, fatigue is multifaceted. Is it cognitive fatigue? Is it physiological fatigue? These are some of the gaps in our knowledge that research needs to address. If we are able to better measure it, we can find treatment targets to target it. [An] example [is] some of the complementary medicines like anti-myostatins that are supposed to increase muscle force. Are the current SMA scales the best way to measure the mechanism of action of the drug? Should we better measure muscle force production? Power? We don't want the lack of the measurement to cause a possible failure to prescribe complementary treatment for these patients.

Reference

1. DeSimone GT. The tortoise factor — get FITT. ACSMs Health Fit J. 2019;23(2):3-4. doi:10.1249/FIT.0000000000000456