New treatment avenue identified for devastating childhood genetic motor neuron disease
Spinal muscular atrophy (SMA) is a devastating disease affecting one in 6,000 children. It is a childhood motor neuron disease which, if left untreated, can be fatal: children born with SMA die within the first two years of life. Researchers at Columbia University have made a groundbreaking discovery that sheds new light on the origins of this disease, which has been studied by neurologists for decades. The study confirms that a genetic defect lead to SMA and suggest a new way to treat the disease. Almost all cases of SMA are caused by a mutation in a single gene – SMN1 (survival motor neuron 1) – che reduces the amount of SMN protein inside motor neurons. SMN protein deficiency damages neurons, which eventually lose the ability to control the body’s muscles.
The Columbia University research team led by SMA researcher Umrao Monani found that SMN deficiency usually damages neurons by affecting a different protein called Hspa8, which helps assemble a critical communication link between motor neurons and muscle cells. If Hspa8 is down, communication links are never built and messages cannot be sent from the neuron to the muscle. Muscles cannot contract without receiving these messages and eventually deteriorate. However, the team also found that some SMA-affected mice were less affected by the disease and stronger. These mice harbored a specific variant of the gene Hspa8 which was not impaired by SMN deficiency. Converting Hspa8 to its variant, the researchers were able to obtain a significant neuromuscular recovery and an increase in survival in mice affected by severe SMA. The treated mice survived for about 300 days compared to only 10 days for the untreated mice.
This groundbreaking discovery suggests a potential new treatment for SMA that could have a powerful effect in people, if the researchers’ experiments in mice are any indication. Monani explains that a treatment that mimics the protective effect of the Hspa8 variant could be developed to help patients. However, more studies are needed to determine how best to translate the findings into a new treatment for SMA.
SMA currently has no cure, and treatment options that increase the production of the SMN protein are still under development, including gene therapy that inserts a new SMN gene into motor neurons. While these therapies are effective in some patients, they don’t work for everyone, can have significant side effects, and are still new, so it’s unclear how long they will last. The discovery by the Columbia University researchers provides valuable insights into the origins of SMA and a potential new treatment option. Their work underlines the importance of continuing research in the field of neuromuscular diseases and the search for new treatments and cures.
