In the third installment of my “Cure in Progress” series, I’m excited to share a key finding from the GRI Census: the top treatment priorities identified by our community. The data reveals that Epilepsy and Intellectual Disability are the most important symptoms to prioritize for treatment, giving us a clear focus for our interactions with researchers and drugmakers.
Why the Census Matters
The census is a powerful tool for our community. By counting every child’s gene, variant, location, symptoms and priorities, we’re building a stronger case for researchers and biotech companies to focus on our specific disorders. A larger, well-documented patient population makes a disease more attractive for study, increases the likelihood of variants being researched in cell and animal models, and helps attract clinical trials to regions with existing patient groups. Most importantly, it ensures that the symptoms and treatment priorities that matter most to families are the ones prioritized for new therapies.
Census Findings
We launched the census on August 1, 2024, and it was made available in eleven languages. With support from GRIUK, GRI France, GRI Italia, and GRIN Europe, we received 441 responses. We then excluded variants that were unverifiable, or classified as “benign” or “variants of uncertain significance” and performed analysis on a final set of 327 responses.
The demographics of our respondents were almost exactly 50% male/ 50% female.
The majority of respondents were from North America (56%), followed by Europe (30%) and the Asia-Pacific region (13%).
Most individuals included in the census (95%) were under 20 years old.
The responses varied by gene: GRIN2B (116), GRIN1 (91), GRIN2A (57), GRIA2 (27), GRIA3 (13), GRIN2D (8), GRIA1 (7), GRIK2 (6), and GRIA4 (2).
GRI Symptoms and Patient Priorities
The most common symptoms, experienced by more than 75% of people with GRI Disorders, are:
Developmental delay
Speech delay or disability
Fine motor delay or disability
Gross motor delay or disability
Intellectual disability
Muscular issues (such as hypotonia / low muscle tone)
Just over half (52%) of respondents have or have had epilepsy, but the prevalence varies greatly by gene: GRIN2D (88%), GRIN2A (74%), GRIA3 (62%), GRIN1 (55%), GRIA2 (44%), GRIA1 (29%), and GRIK2 (17%). (Note: We did not break out GRIA4 because there were only two responses, and the percentages for genes with smaller sample sizes – GRIN2D, GRIA3, GRIA1, and GRIK2 – might not hold true for a larger group.)
When asked to name the top symptom to “prioritize for treatments and cures,” 27% of respondents identified epilepsy as their top priority. Intellectual disability was the next most common top priority at 19%, followed by speech (11%), mood/behavior (10%), and developmental delay (6%).
The top five list was consistent across both GRIN and GRIA.
| GRIN | GRIA | |
| Epilepsy | 26% | 34% |
| Intellectual Disability | 18% | 20% |
| Speech | 11% | 14% |
| Mood/Behavior | 10% | 12% |
| Developmental Delay | 6% | 6% |
This gives us a clear roadmap to follow for further research and in discussions with drugmakers to identify success metrics for clinical trials.
Top Existing Treatments
The most commonly tried treatments were physical, occupational, and speech therapies, plus medicines for epilepsy and gastrointestinal symptoms. But when we asked respondents to tell us if these treatments helped, the result was a mixed bag. Physical and occupational therapies were generally helpful (71% and 66% respectively). But success rates were lower for other top interventions including speech therapy (58% success rate), epilepsy medicines (56%), and gastrointestinal medicines (58%). These numbers suggest that there’s a huge unmet need in successful treatments and medicines for people living with GRI Disorders.
We also asked respondents to identify specific medicines and supplements that seemed to work. The most commonly mentioned were Melatonin (a supplement that helps with sleep), Miralax (a GI medicine), L-Serine (a supplement that may help some loss-of-function GRIN patients), Valproic Acid (used to treat epilepsy), and Perampanel / Fycompa (which may help some gain-of-function GRIA patients).
What’s Next for the Census
We are accepting new census responses, following up with respondents who didn’t upload genetics reports, and collaborating with our research partners to try to reclassify some variants of uncertain significance as pathogenic so we can include them in the dataset. We’ll be using this expanded dataset to write a paper for publication in a scientific journal that will delve into the data on family priorities, including how these priorities vary by age of respondent.
We will also be reaching out to GRI Census respondents who said they want to hear about research opportunities to set them up for blood collections for an industry-sponsored proteomics study.
Finally, we’re excited to announce that we are planning to translate the census into Arabic and Hindi in 2025 to reach more families around the world.
Ready to Participate?
If you haven’t yet, it’s not too late to add your family’s information to the count. You can participate in the CureGRIN Census by visiting curegrin.org/gricensus.
Thanks for helping us to Cure GRIN, GRIA, GRIK and GRID Disorders!
Keith McArthur
Executive Director
CureGRIN Foundation
