At the DNM1L Foundation, we often hear a big question from families: “Why isn’t the foundation pursuing gene editing like CRISPR?” It’s an excellent question, and it comes from a place of hope. In recent years, gene-editing breakthroughs (like a CRISPR cure for a baby’s liver disease) have made headlines, so it’s natural to wonder if the same could be done for DNM1L-related disorders. To answer this, we need to look at three different treatment strategies we’re considering: 1) gene editing, 2) ASO (antisense oligonucleotide) therapy, and 3) drug repurposing. Each approach has its promise and its challenges. Let’s walk through them at a high level and explain why drug repurposing is currently our most practical and hopeful path forward.
Gene Editing: Exciting Potential, But Why Not for DNM1L (Yet)?
Gene editing (like CRISPR-Cas9 technology) is one of the most exciting medical breakthroughs of our time. In early 2025, doctors used a CRISPR-based therapy to successfully treat an infant with CPS1 deficiency, a life-threatening metabolic liver disease. This remarkable case showed that a precise DNA fix in the liver can reverse a deadly condition. It’s no wonder families ask if we could do something similar for DNM1L disorders.
So why aren’t we jumping on CRISPR for DNM1L right now?
The primary hurdle is delivery. In liver disease, CRISPR can reach enough cells in a relatively small and accessible organ. In contrast, DNM1L disorders affect the central nervous system, including the brain and spinal cord, which consist of billions of neurons spread throughout the body. Current technology doesn’t allow for gene editing tools to be safely and effectively delivered to a large enough portion of the brain to make a meaningful impact.
Moreover, the blood-brain barrier—which protects the brain from toxins—also blocks most gene editing tools from getting in. Scientists are actively exploring ways around this, like using nanoparticles or specialized viral vectors, but as of 2025, editing genes in the brain at scale is not yet feasible.
So while we are optimistic about the future of gene editing, and it may eventually play a role in treating DNM1L, it’s not the right approach for our community today.
ASO Therapy: Hopeful Ideas with Hurdles to Overcome
Antisense oligonucleotide (ASO) therapy is another promising area. These short DNA or RNA strands can attach to RNA in cells and help change how genes are read. In some rare conditions like spinal muscular atrophy (SMA), ASO therapy has been life-changing.
But ASO therapy comes with challenges for DNM1L:
Delivery: ASOs don’t naturally cross the blood-brain barrier. To treat the nervous system, they need to be injected directly into the spinal fluid through a procedure called an intrathecal injection. These injections must be repeated regularly—sometimes every few months—for life.
Cost: Each dose of an ASO therapy like nusinersen (used for SMA) costs hundreds of thousands of dollars per year. The costs and logistics of lifelong treatment are simply not feasible for many families or small rare disease foundations.
Specificity: ASOs often need to be tailored to specific mutations. Since DNM1L mutations vary from person to person, we’d potentially need a unique ASO for each patient. This makes it difficult to create a broadly applicable treatment that helps the whole community.
In short, while ASO therapy may help in the future, it’s not broadly scalable or practical for DNM1L today. We’re keeping an eye on the research, but we’re focused on approaches that can help more people sooner.
Drug Repurposing:
The Practical and Hopeful Path Forward
Of all the options, drug repurposing is the most promising path for immediate impact. Drug repurposing means taking medications already approved for other conditions and testing them to see if they can help in new ways.
Here’s why we’re so excited about it:
- Speed: Repurposed drugs have already gone through safety testing, so they can move into clinical trials much faster than new drugs or gene therapies.
- Cost: Developing a new drug from scratch can take over a decade and cost billions. Repurposing cuts those costs dramatically, making it a realistic approach for small foundations like ours.
- Safety: Since these drugs are already FDA-approved, we have a strong understanding of their side effects, risks, and how they interact with the body.
- Scalability: Repurposed drugs often work across multiple patient types. Unlike gene or ASO therapies, we’re not limited to specific mutations. One repurposed drug could potentially help many people with DNM1L-related conditions.
In fact, we’ve already started! In collaboration with Perlara PBC and PhenoVista Biosciences, we’ve launched a Phase 1 feasibility study. Early results show that cell painting—a powerful imaging technique that captures subtle cellular differences—can distinguish between healthy and DNM1L-affected cells. This breakthrough gives us a clear foundation for screening and identifying potential drug candidates in the next phase of our research.
Staying Hopeful and Connected
We know families are eager for answers and hope. So are we. We’re inspired by breakthroughs in gene editing and ASOs, and we’ll continue to follow and support them. But for today—for the families who need help now—drug repurposing gives us the best shot at meaningful progress.
We promise to keep you informed, keep pushing forward, and keep listening.
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Our Mission
By highlighting ongoing research, sharing advancements, and emphasizing the importance of financial support, we aim to inspire our readers to take action in this fight against DNM1L. We look forward to a future where scientific breakthroughs bring relief, hope, and answers to those living with this rare condition.
