Potential Relationship Found Between Early Non-neuromuscular Symptoms and the Lack of SMN Protein in SMA Patients

A direct relationship may exist between early non-neuromuscular symptoms and the lack of survival motor neuron (SMN) protein directly linked to spinal muscular atrophy (SMA), a study reports.

The findings of the study, “Systemic nature of spinal muscular atrophy revealed by studying insurance claims,” were published in PLOS One.

SMA normally is caused by mutations in the SMN1 gene, which provides instructions for making the SMN protein that is essential for motor neuron survival.

“However, growing evidence demonstrates that SMN has a broader role across cell types and physiological systems, such as cardiovascular, intestinal and skeletal, indicating that SMA may be a multi-system disorder. [T]here is reason to believe that a more complete system-wide physiological understanding of SMA and a greater understanding of its temporal progression will be valuable,” the investigators wrote.

In this study, a group of researchers from Harvard Medical School and their collaborators set out to investigate if SMA patients also experience non-neuromuscular symptoms, and whether these symptoms can be detected before the first signs of neuromuscular degeneration, typical of SMA, emerged.

The study was based on insurance claims that were obtained from a de-identified database from Aetna. In total, the study gathered and analyzed insurance claims from 1,038 SMA patients and 39,214,424 healthy controls.

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SMA patients were divided into three groups: group A representing patients who were likely to have type 1/2 SMA and were diagnosed before two years of age; group B representing patients who were likely to have type 3 SMA and were diagnosed between the ages of 2-21 years; and group C representing patients who were likely to have type 4 SMA and were diagnosed between the ages of 21-65. Healthy controls for each SMA group were selected to match the range of patients’ ages.

Researchers analyzed claims from the entire insurance coverage period and claims from patients before receiving their diagnosis or experiencing signs of neuromuscular degeneration, to look for other symptoms that could be related to low SMN levels before the onset of SMA.

Results from the entire insurance coverage period showed that SMA patients had been diagnosed with a wide variety of non-neuromuscular symptoms, including cardiovascular disease (heart disease), metabolic disorders and sensorial defects. These were in addition to the typical symptoms of SMA (e.g., muscle weakness, reduced mobility, respiratory and feeding complications). The prevalence of non-neuromuscular symptoms was much higher in SMA patients compared to healthy controls during the entire coverage period.

In addition, insurance claims from patients before the onset of SMA confirmed the presence of several non-neuromuscular symptoms affecting the heart, bones, gastrointestinal (GI) tract and reproductive organs.

“This points not only to a primary relationship of [non-neuromuscular] symptoms with SMN deficiency, but also towards the possibility of their use in predicting time to neuromuscular symptom onset for treatment initiation prior to irreversible nervous system damage in later stage patients who may not have been screened at birth or who want to delay treatment while they remain asymptomatic,” the researchers wrote.

“Given the extended lifespan of patients treated by SMN increasing therapeutics [e.g., Spinraza], our data may provide insights into other physiological systems that will need dedicated care,” they added.