Individuals with Spinal Muscular Atrophy Treated with Survival Motor Neuron-Targeted Therapies Struggle with Fatigue and Quality of Life

Individuals with Spinal Muscular Atrophy Treated with Survival Motor Neuron-Targeted Therapies Struggle with Fatigue and Quality of Life

Disease-modifying therapies have opened new avenues for individuals with SMA, improving survival, disease course, and motor function. Despite significant advances in therapy, many people affected by this condition continue to experience reduced quality of life and limited mobility. A systematic literature review presented at the 2024 MDA Clinical and Scientific Conference in Orlando, Florida, showed that patients treated with survival motor neuron (SMN)-enhancing therapies report unmet medical needs, particularly a lack of improvement in fatigue and decreased energy levels.  

While the three SMN-targeted therapies approved for the treatment of SMA address the neuronal component of the disease, they do not improve muscle weakness, leaving individuals with SMA to face many limitations when it comes to daily functioning and quality of life. The authors reviewed studies published between 2011 and 2023 in three medical databases to identify and assess unmet medical needs in patients with SMA. The 42 included publications revealed significant improvements in SMA disease course, including longer survival, lower rates of hospitalization, and improved motor function in individuals with SMA treated with SMN-targeted therapies. The degree of improvement in motor strength and motor function varied among publications. Adults and children treated with nusinersen over a period of 10 to 14 months had changes in the Hammersmith Functional Motor Scale—Expanded (HFMSE) ranging from -1 to +6 points (Coriatti G et al; Orphanet J Rare Dis 2021; 16:430). Decreased quality of life, reported in 14 reviews, was the main unmet need for patients with SMA. Many of the included studies also signaled a need for improvement in fatigue and daily activities, including personal hygiene, dressing, feeding, and walking.

“There is a limit on how much we can do for patients with SMA,” said author Diana Castro, MD, who presented the data in a poster session. “Strength-wise we are helping them a lot. But there is a percentage of patients with fatigue that gets them down through the day.” Both adults and children with SMA struggle with fatigue, which affects their work and school performance. Addressing this therapeutic gap is one way to improve quality of life and activities of daily living for individuals with SMA, Castro noted.

Myostatin pathway inhibitors have been shown to increase muscle mass and affect the sensory neural circuits that may enhance motor neuron function in animal models (Zhou H et al; J Cachexia Sarcopenia Muscle 2020; 11:768-782). Although this emerging therapeutic intervention may have limited benefits in humans, it could help some patients with SMA. “It is not a perfect solution, but we are getting closer to where we should be,” Castro said. “In clinic, families report improvements in their children. Now we treat patients with SMA early due to newborn screening, but some do not respond to gene therapy. Those are the ones who need the extra push.” Castro treats 75 patients with SMA at the Neurology and Neuromuscular Care Center, a nonprofit neuromuscular clinic in Dallas, Texas.

The analysis also highlighted the need for more sensitive scales to measure improvement in disease course for patients with SMA. “The question is how can we better measure fatigue, how can we measure those things that happen at home and [are not observed] in the clinic,” Castro added. Although the HFMSE and Revised Upper Limb Module are useful in clinical assessments, they do not reflect small changes that patients observe after initiating SMN-enhancing therapies.

“The current published literature likely underestimates the true burden of SMA in terms of impact of the disease on functional status, activities of daily living, and health-related quality of life,” the authors concluded.