Posted by: Ricardo Ramirez
A message from Ricardo Ramírez, PhD, Chief Scientific Officer of The MED13L Foundation — with the latest updates on our progress and achievements.
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Dear MED13L families and supporters,
We are writing to share an update on the research programs the Foundation is advancing on behalf of your children and loved ones. Over the past year, our scientific efforts have grown from early-stage laboratory work into a coordinated research strategy that spans clinical data collection, drug discovery, biomarker development, and gene therapy. Below is a plain-language summary of where each program stands today, what comes next, and how your continued participation makes all of it possible.
1. Natural History Study (ACTION for MED13L)
Status: Happening Now
What is a natural history study?
A natural history study is a carefully designed research program that follows individuals with a condition over time. The goal is to understand how MED13L Syndrome presents and changes as our children grow, what skills develop, what challenges persist, and how different aspects of health are affected at different ages. This kind of data is essential because it gives doctors and researchers a detailed picture of the condition that simply does not exist yet for MED13L Syndrome.
Why does this matter?
Before any treatment can be tested in a clinical trial, regulators such as the FDA require evidence that researchers understand the natural course of a condition. Natural history data helps answer critical questions: How do we measure whether a treatment is working? What outcomes should a trial track? What does a typical trajectory look like so we can recognize improvement? Without this foundation, clinical trials cannot move forward. In short, the natural history study is the bridge between laboratory discoveries and real treatments reaching your children.
Where we stand
Our ACTION for MED13L study at Boston Children’s Hospital, led by Dr. Maya Chopra, has made tremendous progress:
- We have 29 individuals fully enrolled, and our 30th participant is currently completing their consent process.
- Year 1 data collection, including completion of all neurobehavioral assessments, is complete for 26 participants.
- The remaining participants have their visits scheduled within the next month.
This is a remarkable pace of enrollment and reflects the dedication of every family who has traveled to Boston, completed interviews, undergone assessments, and shared their child’s medical history with our research team.
We expect to have a more detailed update on Year 1 findings by June. Stay tuned as this will be the first time we can begin to share what the data is showing us about MED13L Syndrome as a whole.
How you can help us
This study runs on your participation. Every assessment completed, every follow-up visit attended, and every questionnaire returned adds to the dataset that will ultimately define what “clinical trial readiness” looks like for MED13L Syndrome. If you are enrolled, please stay engaged — your ongoing participation across all three years of the study is critical. The data from Year 1 is only meaningful when we can compare it to Years 2 and 3, so returning for follow-up visits is just as important as the first one. If you have not yet enrolled and are interested, please reach out to us.
2. Drug Repurposing
Status: Active Research Now — Observational Trial Targeted for 2027
What is drug repurposing?
Drug repurposing is a strategy where researchers look at medications that are already approved and well-understood for other conditions and investigate whether they might also help with MED13L Syndrome. Because these drugs have already been proven safe in people, sometimes for decades, they can potentially reach our children much faster than a brand-new drug developed from scratch, which can take 10 to 15 years.
What we’ve found
Through a combination of iPSC-derived neuron studies (where we grow brain cells from patient-donated samples) and analysis of plasma protein biomarkers, our research team has identified a promising drug candidate: a common NSAID (non-steroidal anti-inflammatory drug) that appears to address some of the biological differences we see in MED13L cells. This candidate emerged independently from two separate lines of evidence, which increases our confidence in the finding.
Important: This research is still in the laboratory and early analysis stage. We are not recommending or consenting anyone to take any medication at this time. Please do not start, stop, or change any medication based on this update. Always consult your child’s physician before making any decisions about medications.
What comes next: Observational trial in 2027
Our plan is to advance this candidate toward an observational trial, which we are targeting for 2027. An observational trial is an early-stage clinical study where participants take a medication under medical supervision while researchers carefully track health outcomes, safety, and biological markers over time. Unlike a traditional randomized clinical trial, an observational trial is designed to gather initial real-world evidence about whether a drug shows meaningful effects in our specific population. This is an important and necessary step before a larger, controlled trial.
Mitochondrial drug screening
In parallel, we are conducting early-stage drug screening focused specifically on the mitochondrial effects of MED13L Syndrome. Research in our partner laboratories has shown that MED13L loss affects mitochondrial function, the energy-producing machinery inside cells. We are currently screening existing drugs to see if any can correct these energy deficits. If we identify drugs that show meaningful and safe effects, this could open the door to a second observational trial focused on mitochondrial rescue.
3. Clinical Biomarkers
Status: Active Research Now — Validation Underway
What are biomarkers?
A biomarker is a measurable indicator in the body, such as a protein in the blood, that tells us something about a person’s health or how they are responding to a treatment. For MED13L Syndrome, having reliable biomarkers would be transformative. They would allow us to measure, through a simple blood draw, whether a treatment is having the intended biological effect, without having to wait months or years for observable clinical changes.
Where we stand
Through our proteomics research, a large-scale study of thousands of proteins in blood samples from individuals with MED13L Syndrome and matched controls, we have identified a set of candidate biomarkers that appear to reliably distinguish individuals with MED13L Syndrome from the general population. Many of these proteins are tied to immune and inflammatory pathways, which aligns with what families and clinicians observe.
What “validating” means
We are now working on validating these candidate biomarkers. Validation means confirming, through independent testing methods and in additional patient samples, that these protein differences are consistent and reliable, not just a one-time finding. This is a necessary step before biomarkers can be used in clinical settings or as endpoints in a drug trial. Think of it as making sure our “measuring stick” is accurate before we use it to evaluate treatments.
How you help us: The biorepository
Biomarker validation depends on having enough samples from enough individuals to confirm our findings. If you have the opportunity to contribute biological samples (such as blood) to the Foundation’s biorepository, please consider doing so. We are continuously working to build out this resource, and every sample donated strengthens our ability to validate biomarkers, power future studies, and accelerate the timeline toward treatments. The biorepository is one of the most tangible ways families can directly contribute to research progress.
4. MED13L Gene Therapy (CRISPRa)
Status: Long-Term — Proof-of-Concept Development Underway
What is CRISPRa gene therapy?
While drug repurposing and biomarker development are our near-term priorities, the Foundation is also investing in longer-term therapeutic approaches that aim to address the root cause of MED13L Syndrome. Most individuals with MED13L Syndrome have the condition because one of their two copies of the MED13L gene is not working properly, a situation called haploinsufficiency. The remaining healthy copy is still there, but it doesn’t produce enough MED13L protein on its own.
CRISPRa (CRISPR activation) is a gene therapy technology that can turn up the activity of the remaining good copy of a gene, essentially telling the healthy copy to work harder and produce more protein. Importantly, CRISPRa does not cut or edit DNA. It uses a deactivated version of the CRISPR tool to gently boost gene expression, making it a potentially safer approach than traditional gene editing. In simple terms: we are trying to turn MED13L back on.
Where we stand
In partnership with Dr. Nadav Ahituv’s laboratory at the University of California, San Francisco (UCSF), we are currently developing CRISPRa constructs specifically designed for MED13L. Dr. Ahituv’s lab has already demonstrated that this approach can successfully rescue a similar haploinsufficiency condition (SCN2A) in both human neurons and mouse models. They have now turned their attention to MED13L and are actively working on optimizing the molecular tools needed to boost MED13L expression in human and mouse cells.
This work is still in the proof-of-concept stage — the team is identifying the best molecular guides (sgRNAs) and packaging them into delivery vehicles (AAV) that can reach brain cells. Once validated, these tools will be shared with our collaborating laboratories worldwide for testing in cell and animal models of MED13L Syndrome.
Why this matters
Gene therapy represents the most direct approach to treating the root cause of MED13L Syndrome. While it is further from the clinic than drug repurposing, every step we take now — developing the constructs, testing in cells, validating in animal models — brings us closer to a future where a targeted genetic treatment for MED13L Syndrome is possible. The natural history data, biomarkers, and drug repurposing work described above are not separate from this goal; they feed directly into it by providing the clinical infrastructure needed to eventually test gene therapies in people.
How you can help us
Gene therapy development depends on all of the earlier programs succeeding. The natural history data defines the clinical endpoints a gene therapy trial would need to measure. The biomarkers give us a way to detect biological changes. The drug repurposing work builds the clinical trial infrastructure and regulatory relationships we will need. Your participation in the natural history study, your biorepository donations, and your engagement with the Foundation are all directly building the path toward this long-term goal.
How It All Connects
These four programs are not isolated efforts — they are designed to build on each other:
- Natural history data (Happening Now) tells us what to measure in a clinical trial.
- Drug repurposing (Active Now → Possible aim to design trial in 2027) gives us the fastest path to a treatment families can access.
- Biomarkers (Active Now → Validation Underway) give us a way to measure treatment effects through a blood test.
- Gene therapy (Long-Term) is the ultimate goal of addressing the root genetic cause.
Each piece makes the others stronger. The natural history study and biomarker work create the foundation for any future clinical trial — whether that trial tests a repurposed drug or, eventually, a gene therapy. Your participation in the natural history study and contributions to the biorepository are directly enabling all of these efforts.
Thank You
None of this work is possible without the MED13L community. Every family that has enrolled in the natural history study, donated samples, traveled to research sites, or simply stayed engaged with the Foundation’s mission is contributing to a research program that did not exist just a few years ago. We are building something real, and we are building it together.
We will continue to share updates as milestones are reached. If you have questions about any of the programs described here, please do not hesitate to reach out to us.
Ricardo N. Ramirez, PhD
Chief Scientific Officer, the MED13L Foundation
