At A Foundation Building Strength (AFBS), our $3.6 million research investment is currently fueling several high-impact projects aimed at one goal: finding effective treatments for Nemaline Myopathy. Today, we’re thrilled to share the latest progress from our second year of funding for Dr. Coen Ottenheijm and his team (Amsterdam University Medical Center (UMC), Radboud UMC, Leiden UMC, Netherlands), who are working on a groundbreaking therapy for KBTBD13-related Nemaline Myopathy, also known as NEM6, or Nemaline Myopathy type 6.
The Road to Discovery: Understanding KBTBD13-related NM
KBTBD13-related Nemaline Myopathy is a distinct form of the disease. While many types of NM involve general muscle weakness, KBTBD13-related NM—first described by Dr. Ottenheijm’s group in 2002—is unique for its “slow relaxation” of muscles. This makes everyday movements, like releasing a grip or stepping forward, significantly more difficult.
After identifying the gene responsible (KBTBD13) in 2010, and unraveling how genetic errors lead to this slow relaxation in 2020, the team developed a specialized mouse model. This allowed them to move from observation to intervention.
Recap: Year One Milestones
The first year of this AFBS-funded project was dedicated to mapping the “natural history” of the disease in mice. The team discovered that while the mice appear asymptomatic for the first month, they develop a strong “phenotype” (visible symptoms) by month three. This established a critical timeline:
- Month 1: The window to test if the disease can be prevented.
- Month 7: The window to test if the disease can be reversed.
Year Two Breakthroughs
We are incredibly excited to report that the second year of research has yielded spectacular results. Dr. Ottenheijm’s team has been testing a treatment that utilizes a harmless, engineered virus (AAV9) to deliver a genetic tool called short hairpin RNA (shRNA). This tool is designed to “knockdown” or reduce the amount of the harmful KBTBD13 instructions inside the muscle cells.
The results of the AAV9-shRNA intervention were highly effective:
- Prevention: When administered early (at 1 month), the therapy fully prevented the onset of muscle disease.
- Restoration: Even more remarkably, when given to mice with advanced disease (at 7 months), the treatment completely restored muscle morphology and contractility. In other words, the therapy didn’t just stop the disease from getting worse—it helped the muscles function normally again, even after the disease was well-established.
Refining the Future: Precision and Broad Reach
With these successful results in hand, the research is now expanding in two vital directions:
- Allele-Specific Therapy: Because KBTBD13-related NM is a dominant condition (where only one mutated copy of the gene causes the disease), the team is refining the treatment to target only the mutant version of the gene. This “allele-specific” approach ensures the healthy copy remains untouched, further increasing the safety of the treatment.
- Broad Applicability: To ensure this treatment works for everyone with KBTBD13-related NM, the team is testing it against different genetic variants, such as the G67R variant. This will confirm if the benefits seen so far can be generalized across the entire NEM6 patient population.
Powered by You
This progress is made entirely possible by the support of our individual donors. At AFBS, we maintain a unique commitment: 100% of every individual donation goes directly to research. Your contributions are the lifeblood of projects like Dr. Ottenheijm’s. Because of you, we are currently funding nine active research projects that are moving us closer to a future of effective treatments for Nemaline Myopathy.
Together, we are building strength—one breakthrough at a time.
A Foundation Building Strength (AFBS) is a nonprofit organization dedicated to accelerating the development of treatments for Nemaline Myopathy. Our mission is to fund cutting-edge research to find effective treatments while providing resources and a strong community for families affected by NM. We are proud to be at the forefront of driving Nemaline Myopathy research breakthroughs forward through collaborations with research teams across the globe.
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