22nd July 2024

Biomarkers are medical indicators that can be measured to show the severity, progression and response to treatment of a condition. Having more SMN2 gene copies is generally associated with less severe SMA symptoms. However, at an individual level, a person’s SMN2 copy number on its own does not give an accurate prediction about the type or severity of their SMA. Researchers are always looking for better measures and additional genes or proteins that can be useful for diagnostic and treatment purposes.

A recent study led by Professor Heidi Fuller at Keele University looked at the levels of different proteins found in skin cells (fibroblasts) taken from people with varying severities of SMA.

The researchers sought to understand how the availability of different proteins in fibroblasts of people with SMA type I, II and III can vary.

Surprisingly, fibroblasts from patients with different types of SMA (severe, intermediate, mild) showed limited overlap in the proteins that are present. This suggests that SMN can impact the production of other proteins, and that differing SMN levels have differing impacts.

Among the three types, fibroblasts from patients with SMA Type II showed the greatest variability in production of proteins. This was not explained by the number of SMN2 gene copies, which is a known modifier of SMA severity.

Despite the limited overlap in specific proteins, some common biological pathways were affected across the different types of SMA. These included processes related to protein synthesis and degradation, cellular stress responses and energy production.

Some specific proteins had expression levels that could potentially serve as biomarkers for distinguishing between the different severities of SMA. In the future, these biomarkers may prove helpful in patient stratification and monitoring treatment responses.

When fibroblasts from SMA patients were treated to increase SMN protein availability, only the expression of one protein in SMA II fibroblasts showed a significant response. This suggests that the effectiveness of treatments may vary depending on SMA type.

This research further highlights the complexity of SMA and the need for personalised approaches to treatment. By understanding the specific protein changes associated with each type of SMA, better diagnostic tools and targeted therapies may be developed.

The study provides valuable insights into the molecular underpinnings of SMA and underscores the importance of considering disease severity when developing and evaluating therapeutic strategies.

Reference

Brown SJ, Kline RA, Synowsky SA, Shirran SL, Holt I, Sillence KA, Claus P, Wirth B, Wishart TM, Fuller HR. The Proteome Signatures of Fibroblasts from Patients with Severe, Intermediate and Mild Spinal Muscular Atrophy Show Limited Overlap. Cells. 2022 Aug 23;11(17):2624. (pdf)