How close are we to curing GRI Disorders?
Welcome to the inaugural edition of our Cure in Progress Report! As the Executive Director of CureGRIN Foundation, I’m thrilled to launch this new way of connecting with you. My goal with this report is to provide you with transparent, hopeful, and regular updates on the progress being made towards treatments and cures for GRI Disorders.
Last month, a bit of a kerfuffle erupted in online forums when a researcher shared exciting news about a “first of its kind” treatment for GRIN2B Disorders. Understandably, many families, filled with hope, interpreted this as a cure being just around the corner. While the enthusiasm was palpable, it also highlighted a crucial distinction: not every groundbreaking discovery immediately translates into a ready-for-patient cure. The research, which answered a fundamental question in GRI research – whether some of our genes are too large for gene editing (the answer, thankfully, is a resounding ‘no’!) – is an important step forward. We celebrate every bit of progress, but it underscores that even the most promising breakthroughs require extensive further development and regulatory pathways before they can reach our loved ones. This brings us to the question we all ask: “How close are we to curing GRI Disorders?”
It’s a complex question without a simple answer, but it’s one that fuels our every effort at CureGRIN. Today, I want to share a realistic, yet optimistic, perspective on where we stand, and why I believe we are closer than you think.
Breakthroughs in other rare neurological disorders are providing a roadmap. We’re hearing first-hand accounts from parents whose children are experiencing incredible improvements after targeted treatments. A powerful example comes from the SCN2A community: 15-year-old Connor Dalby — whose mom Kelley is a keynote speaker at GRICON next month — walked for the first time in his life after his second ASO treatment. These ASO treatments, which are special medicines designed to fix or adjust how our genes work, show immense promise. Nonprofit N-Lorem is preparing to treat a GRIA1 patient with ASOs in the near future. What makes ASOs particularly exciting for GRIN1 Disorder is that usually, having only one working copy of the GRIN1 gene doesn’t cause symptoms on its own. This means that ASO treatments could potentially help patients whose GRIN1 gene is working either too much (gain-of-function) or not enough (non-functional loss-of-function). This wide ability to help means it’s possible that just 3 or 4 ASOs could work for most GRIN1 patients. These developments mean that technologies and therapeutic approaches are maturing rapidly, offering new hope for GRI Disorders.
We are firmly in an exciting and critical phase, making us closer than ever to real solutions:
- Imminent Clinical Trials for GRI Disorders: GRIN Therapeutics is on track to initiate a global, pivotal Phase 3 clinical trial for Radiprodil in mid-2025. This investigational drug, a selective modulator of the NMDA receptor, has shown promising results in earlier phases for GRI-related neurodevelopmental disorder with gain-of-function (GoF) variants, particularly in reducing seizure frequency. This is a monumental step forward.
- Pioneering Gene Therapies and Gene Editing: At least five labs across the US, Canada, Israel, and Turkey are actively engaged in preclinical work on gene therapies or gene editing strategies specifically for GRIN1, GRIN2A, GRIN2B, and GRIN2D. These efforts represent a significant push towards truly curative approaches, aiming to correct the underlying genetic causes of GRI Disorders.
- Broader Pharmaceutical Engagement: Beyond GRIN Therapeutics, other companies are developing medicines targeting neurological receptors like NMDA, AMPA, and Kainate. CureGRIN works closely with them, advocating how their therapies could benefit GRI Disorders. A significant development is that three companies in COMBINED Brain’s industry consortium have identified GRI Disorders as a key R&D focus. This means our disorders are eligible for industry-funded studies to identify crucial biomarkers in blood and and EEGs. As a direct result, we plan to collect 125 patient plasma samples this year, with over 20 samples each from individuals with GRIA2, GRIA3, GRIN1, GRIN2A, and GRIN2B.
- Emerging Therapeutic Strategies and Lessons from Other Diseases: Furthermore, two more clinical trials will be open to our patients who experience seizures: Praxis Precision Medicines is advancing Relutrigine (PRAX-562), and Lundbeck (through Longboard Pharmaceuticals) is progressing Bexicaserin (LP352). (A keynote at GRICON will feature executives from all three companies launching Phase 3 trials).
- GRI Census: Our growing patient census provides invaluable data on the natural progression of GRI Disorders, essential for designing effective clinical trials and measuring therapy impact.
Our Role at CureGRIN
CureGRIN Foundation accelerates this progress by leading or funding cutting-edge research, building collaborative networks among researchers, clinicians and industry, advocating for our community, and empowering families. We are actively building a comprehensive “How to Cure GRI Disorders” guide, which will be a vital resource for our community. We are excited to share more details about this at GRICON next month! We will also be sharing the impactful results from our recent GRI Census at GRICON.
A Path Forward, Together
While we cannot put an exact date on a cure, what I can tell you with certainty is that we are closer than ever before. The scientific community is more engaged, the tools at our disposal are more sophisticated, and our community is more united and powerful than ever. Every research grant funded, every data point collected, every family connected, brings us one step closer.
The journey to a cure is a marathon, not a sprint, and it requires sustained effort, significant resources, and unwavering hope. We are immensely grateful for your continued support, which makes all of this work possible.
We invite you to join us in person at GRICON next month in Orlando to learn even more about these exciting developments, connect with other families and researchers, and be part of the accelerating progress towards treatments and cures. Your presence makes a difference!
Thank you for being a vital part of the CureGRIN family. Together, we are building a future where GRI Disorders are treatable, and eventually, curable.
With hope and determination,
Keith McArthur Executive Director CureGRIN Foundation
Stay tuned for our next progress report, where we’ll delve into a specific research breakthrough or initiative!
