Building Strength: Promising Developments in Gene Therapy for Nemaline Myopathy

Research March 12, 2024April 8, 2024

There’s been exciting progress on a new approach treating Nemaline Myopathy (NM), the rare muscle disorder that causes weakness and low muscle tone. While researchers have identified twelve different faulty genes that cause NM and prevent muscles from working properly (ACTA1, NEB, TPM2, TPM3, KBTBD13, CFL2, KLHL40, KLHL41, LMOD3, MYPN, TNNT1, and TNNT3, with the most common being NEB and ACTA1), there are currently no treatments that directly target the cause of the disease.

We have hopes that may change: Dr. Afrooz Rashnonejad’s team at Nationwide Children’s Hospital (with help from a research grant funded by A Foundation Building Strength) is developing a gene therapy specifically for ACTA1-related NM, also known as Nemaline Myopathy 3 (NEM3) and are reporting significant early success 6 months in to their latest research project.

Understanding the Problem:

The ACTA1 gene provides instructions for building a protein essential for healthy muscle function. Mutations in this gene disrupt the protein’s structure and prevent it from working correctly. This, in turn, throws off the balance of other proteins in muscle cells, leading to weakness, reduced muscle mass, and breathing and swallowing difficulties.

A New Hope: Gene Therapy for NEM3

Dr. Rashnonejad’s team is pioneering a gene therapy approach for NEM3. Their strategy involves:

• Silencing the faulty gene: They’ve designed a “tool” (therapeutic genetic construct) to shut down the expression of the mutated ACTA1 gene.
• Introducing a healthy copy: They’ve also created a way to deliver a healthy copy of the ACTA1 gene into muscle cells.

Early Signs of Success:

Initial tests in simple cell models have shown promise. The research team observed a decrease in the buildup of harmful protein clumps, called nemaline rods, when they introduced their therapeutic approach. They’ve also mimicked the disease in lab dishes using human and mouse muscle cells. So far, the findings suggest this gene therapy could be an effective way to treat NEM3.

The Next Steps:

Dr. Rashnonejad and her team of researchers are now scaling up their efforts to test the therapy in live mouse models with NEM3. This will involve creating large quantities of delivery vehicles called AAV vectors, which carries the therapeutic genetic material into muscle cells. They’ll then test different doses to determine the safest and most effective approach.

Building a Brighter Future:

This research on gene therapy for NEM3 holds significant promise. While there’s still quite a bit more work to be done, these early results offer hope for a future where this challenging condition can be treated effectively. AFBS will continue to follow Dr. Rashnonejad’s progress and share updates on this exciting development!