July 24, 2024
Spinal Muscular Atrophy

New Therapeutic Approach Discovered for Spinal Muscular Atrophy

A recent study conducted by Northwestern Medicine has identified a potential new therapeutic strategy for spinal muscular atrophy (SMA), a genetic disease that affects motor neurons. SMA disrupts the nerve cells responsible for controlling voluntary muscle movement, leading to impaired motor function in affected individuals, especially children. SMA is the leading genetic cause of toddler mortality, with most children diagnosed with type 1 SMA not surviving beyond their second birthday.

The molecular mechanisms that trigger the development of SMA are not well understood, making it challenging to develop effective treatments for the disease. However, the study conducted by Northwestern Medicine sheds light on a promising therapeutic avenue. The researchers discovered that modulating the activity of a kinase called cyclin-dependent kinase 5 (Cdk5) in motor neurons could help mitigate mitochondrial defects and alleviate the symptoms of SMA.

The study, published in the Proceedings of the National Academy of Sciences, examined induced pluripotent stem cells from human SMA patients, as well as SMA mice. The researchers found that the activity of Cdk5 was increased in these cells, suggesting its involvement in the development of SMA. To validate their findings, the team genetically knocked out a Cdk5 activator in mice and utilized a pharmacological inhibitor in human cells. Both approaches resulted in a significant decrease in motor neuron degeneration and relief of several symptoms associated with SMA.

The findings of this study provide valuable insights into the molecular mechanisms underlying SMA and point to Cdk5 as a potential target for therapeutic intervention. The researchers also discovered a positive feedback loop between Cdk5 and mitochondrial defects, which ultimately leads to motor neuron degeneration. Notably, this feedback loop is responsible for motor neuron excitotoxicity, a phenomenon observed in various motor neuron diseases, including amyotrophic lateral sclerosis (ALS).

While current Cdk5 inhibitors come with high toxicity risks and low specificity, the researchers hope to develop a bioactive inhibitor that can specifically target the pathway involved in motor neuron degeneration. Additionally, they aim to explore strategies for restoring normal mitochondrial activity, as this could be a promising approach for treating not only SMA but also other motor neuron diseases like ALS.

This study has significant implications for the understanding and treatment of SMA. By uncovering the role of Cdk5 in causing mitochondrial defects and motor neuron degeneration, the researchers have identified a novel pathogenic mechanism that could be targeted for therapeutic purposes. As further research is conducted, this discovery could pave the way for the development of innovative treatments that improve the quality of life for individuals affected by SMA and other motor neuron diseases.

1. Source: Coherent Market Insights, Public sources, Desk research
2. We have leveraged AI tools to mine information and compile it