Progress in SYNGAP1 therapeutic development and the early history of the SYNGAP Research Fund (SRF) chronicled in SRF’s first published paper

Mill Valley, CA – April 25, 2025 – SynGAP Research Fund (SRF) dba Cure SYNGAP1, a 501(c)(3) organization focused on improving the lives of individuals with SYNGAP1-related disorders (SRD), is proud to announce the publication of its first paper, “Roadmap to Advance Therapeutics for SYNGAP1-related disorders: A Patient Perspective,” in Therapeutic Advances in Rare Disease. This review outlines progress in developing SYNGAP1 therapies and the steps taken by SRF over five years to accelerate treatments. 

Our Mission in Publishing This Paper

SRF published this paper to document and share the critical progress made in advancing SYNGAP1 therapeutic development and to share our roadmap for other patient advocacy groups (PAGs) focused on therapeutic development. Grounded in the perspectives of patients and caregivers, this publication emphasizes the unique challenges faced by individuals with SYNGAP1-related disorders (SRD), from developmental delays to epilepsy and behavioral difficulties, offering detailed descriptions of their lived experiences. These narratives are interwoven with an overview of SYNGAP1 biology and the therapeutic landscape, making this paper an essential resource for industry, researchers, clinicians, and advocates alike.

Beyond presenting the current state of research, this paper chronicles the strategic efforts undertaken by SRF to accelerate the development of treatments for SRD. From fostering collaborations between researchers and clinicians to empowering patient advocacy, SRF has worked tirelessly to drive scientific innovation towards patient needs. This publication highlights the contributions of the scientific community working on everything from SYNGAP1 biology to therapeutics and endpoints while showcasing the actionable steps SRF has taken to drive progress.

More than a review, this paper is a call to action for the broader rare disease community. By documenting SRF’s journey and sharing a replicable framework, it offers valuable insights for other PAGs striving to advance research and therapeutic development. It underscores the high-impact uses of both funding and time–whether investing in transformative research, fostering synergistic collaborations, or building connected patient communities–all are essential for accelerating progress. This publication, coupled with SRF’s recently released SYNGAP1 2024 Impact Report, serves as both a testament to the power of patient-led initiatives and a guide for fostering meaningful collaborations, all with the goal of transforming the lives of those living with rare disorders.

Building on a Legacy of SYNGAP1 Research

The publication of this paper marks a major milestone as the first SRF-only publication, authored by J. Michael Graglia, Aaron J. Harding, and Kathryn A. Helde. While all three have prior authorships in this space, this work demonstrates SRF’s growing leadership in SYNGAP1 research. By integrating patient advocacy and therapeutic development, it highlights the unique and essential role of patient-led initiatives in driving progress for rare disorders like SYNGAP1-related disorders (SRD).

This work builds upon decades of foundational SYNGAP1 research, including the landmark review “Twenty Years of SynGAP Research: From Synapses to Cognition”, which provides a comprehensive overview of the role of SYNGAP1 in synaptic function and cognitive development. Key contributions from researchers like Thomas Frazier, PhD, Jillian McKee, MD, PhD, and Helen Willsey, PhD have expanded understanding of SYNGAP1, specifically clinical characterization, therapeutic opportunities, and molecular biology. Additionally, studies led by Richard Huganir, PhD have revealed critical insights into how SYNGAP1 regulates synaptic strength and plasticity, underscoring its importance as a therapeutic target.

This inaugural SRF paper not only synthesizes the work of these pioneers but also forges new ground by amplifying the voices of patients and caregivers. It serves as a bridge between decades of scientific discovery and the urgent need for actionable therapies, while also providing a replicable framework for other advocacy groups to accelerate research. By drawing from and contributing to this rich foundation of research, SRF continues to advance the collective goal of improving outcomes for individuals and families affected by SRD.

Perspectives from SRF and the Rare Disease Community

Kathryn Helde, PhD, Chief Scientific Officer at the SynGAP Research Fund (SRF), emphasizes the importance of the organization’s mission and values, stating, “It was important for our community to understand the breadth and depth of actions our PAG takes to accelerate treatments and reduce suffering for our loved ones. The founders of SRF were intentional in choosing Transparency, Collaboration, and Urgency as the guiding values to achieve our goal of accelerating the availability of safe, effective disease-modifying therapies that are meaningful for our families. I am dedicated to this work based on the mission and values of SynGAP Research Fund, which match my own deeply held goals and ways of working.”

Mike Graglia, Founder & CEO of SRF, said, “This paper, indeed, this series is a valuable resource for the quickly growing number of PAGs seeking to accelerate science for their patients/loved ones.  I am grateful to the editors for including us and I hope SRFs story is helpful to others.”  

“Partnering with Patient Advocacy Groups is critical to the development of potential new medicines,” said Parisa Sanandaji, Vice President of Patient Advocacy & Policy at Stoke Therapeutics, which focuses on addressing the underlying cause of severe diseases by upregulating protein expression with RNA-based medicines. “SRF stands out for its capabilities and collaborative approach, which help reduce risk and accelerate drug development. By sharing patient and caregiver insights, identifying treatment centers, supporting research models, improving clinical trial readiness, and advocating for regulatory support, SRF is demonstrating ways in which PAOs and industry can work together to deliver new medicines that are effective and also meet the needs of patients and their families.”

“SRF’s recent publication is a testament to their unwavering leadership in the rare disease space and a blueprint for patient advocacy groups like ours,” said Jill Hawkins, Founder & President of the FAM177A1 Research Fund, a nonprofit dedicated to advancing research and therapeutic development for FAM177A1-related disorder. “This paper not only highlights the remarkable progress in SYNGAP1 research but also demonstrates the power of patient-driven drug development. By engaging all stakeholders—patients, researchers, and industry—SRF has created a roadmap that serves as one of the most practical guides for emerging patient advocacy groups. Their transparency, dedication, and willingness to share their expertise continue to set the standard in the rare disease community, and we are deeply grateful for their leadership in paving the way for others.”

“This paper serves as a well-organized, evidence-based how-to manual for PAGs like us. It provides invaluable insights into how to strategically fund and invest in research, collaborate with industry and academia, advocate for regulatory changes, enhance patient engagement and data collection, and navigate sustainability challenges,” said Emily Amerson, President of CTNNB1 Connect & Cure, a patient advocacy group dedicated to advancing research and family support for CTNNB1 Syndrome. “Seeing the grant schedule laid out over several years gives such a comprehensive view of research strategy—it’s super helpful. I also had no idea how much direct support to families SRF has been providing. It’s inspiring and gives us tangible ideas to do the same. The paper really highlights the evolution of PAGs becoming more involved in research, which is so important. And the way SRF has balanced diverse funding sources while maintaining prioritization and timing is incredible. This is such a fantastic resource!”

Natacha Pires, MS, MBBS, Executive Director of the Adult Polyglucosan Body Disease Research Foundation, shared, “Kudos to the SRF leadership on this publication! It is an invaluable resource that makes the case for SYNGAP1-related disorders as a compelling therapeutic target while also positioning the SRF and its patient community as a central driver of research and therapy development. This is a resource that could be emulated by all of us in the rare disease advocacy community as we work to advance research and make treatments a reality.”

Family Donations Make Progress Possible

The progress outlined in this paper is a testament to the generosity and dedication of families within the SYNGAP1 community. Family donations fuel the research and initiatives that drive meaningful change for individuals living with SYNGAP1-related disorders. This paper includes tables summarizing the various types of donations that support SRF’s work, highlighting the many ways families contribute to advancing research, awareness, and advocacy.

Anthony Navarro, Resource Mobilization Director, adds, “Our families are the driving force behind everything we do. Their generosity, advocacy, and dedication fuel progress in SYNGAP1 research. Every contribution—whether financial, through advocacy, or by sharing their experiences—moves us closer to effective treatments. This paper reflects not just our funding progress but the collective impact of a community determined to make a difference.”

Importantly, this publication was a volunteer effort, created without the use of donor funds or other financial resources. SRF’s mission is to accelerate the availability of safe and effective treatments that meaningfully modify SRD to reduce suffering for patients and their families. Our current funding priorities include essential milestones for clinical trial readiness.

About J. Michael Graglia, MBA, MA

Mike Graglia is the Founder and Managing Director of the SynGAP Research Fund (SRF), established in 2018 following his son Tony’s diagnosis with SYNGAP1-related disorders. With a background in management and policy, Mike has dedicated himself to accelerating research and therapeutic development for SYNGAP1, emphasizing collaboration, transparency, and urgency. Under his leadership, SRF has raised over $6.2 million to fund critical research initiatives.

About Kathryn A. Helde, PhD

Dr. Kathryn Helde serves as the Chief Scientific Officer and Medical Science Director at SRF. She leads efforts to advance SYNGAP1 research tools and resources, encourages collaborations amongst scientists and clinicians to deepen the understanding of SYNGAP1 biology and develop effective therapies. With a background in genetics and developmental biology, Kathryn’s work is instrumental in bridging the gap between scientific research and patient advocacy. She has three adult sons, one with SRD.

About Aaron J. Harding, MS

Aaron Harding is a board member of the SynGAP Research Fund (SRF) and a dedicated advocate for SYNGAP1 research. His commitment to this work is deeply personal—his son, Jaxon, was diagnosed with SYNGAP1-related disorders, inspiring him to take an active role in advancing research, raising awareness, and building connections within the SYNGAP1 community. Aaron is passionate about ensuring families have access to the resources and support they need while pushing for scientific progress through collaboration with researchers and clinicians. Jaxon’s story continues to drive his advocacy, reinforcing his dedication to making meaningful advancements in SYNGAP1 research and care.

About SYNGAP1-Related Disorders (SRD)

SYNGAP1-related disorders (ICD-10 F78.A1) are a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SYNGAP1 protein levels. SRF has identified over 1,581 patients to date, and the number grows weekly. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SYNGAP1 protein levels are too low, we see an increase in excitability in the synapses making it difficult for neurons to communicate effectively. This leads to many neurological issues seen in SYNGAP1 patients.

Symptoms of SRD include primarily neurological issues including autism spectrum disorder (ASD), intellectual disability, epilepsy, hypotonia (low muscle tone), gross and fine motor delays, global developmental delay, and visual abnormalities such as strabismus (crossed eyes) as well as gastrointestinal challenges and disordered sleep.

About the SynGAP Research Fund

The mission of the SynGAP Research Fund (SRF) dba Cure SYNGAP1 is to improve the quality of life for SYNGAP1 patients through the research and development of treatments, therapies, and support systems.

SRF was founded in the US in 2018 as a 501(c)(3) US public charity.  There are sister organizations founded by local families in the UK in 2020, Europe (Netherlands) in 2022, as well as both Australia & Latin America (Colombia) in 2023. Completely family-led, SRF is a leading funder of SYNGAP1 research having committed over $6.2 million in grants to date.

SRF’s grant program awards one or two-year grants to investigators, physician residents, and clinicians interested in studying SYNGAP1. SRF grants are intended to help researchers explore novel ideas and answer open questions related to the clinical aspects of and therapies for SRD. You can learn more about SRF and their accomplishments by reading their current Impact Report.

For more on SRF, visit curesyngap1.org or follow @cureSYNGAP1 on LinkedIn, YouTube, Instagram, Facebook, TikTok, or X.

SRF is a member of FasterCures, COMBINEDBrain, Global Genes Foundation Alliance, Everylife Foundation Community Congress, Epilepsies Action Network, Personalized Medicine Coalition, Rare Epilepsy Network, Epilepsy Leadership Council, Alliance for Genetic Etiologies in Neurodevelopmental Disorders and Autism (AGENDA), California Action Link for Rare Diseases, American Brain Coalition, Genetic Alliance UK, Rare Disease UK, Syndromes Without a Name (SWAN UK), Jumpstart Program, Patient Worthy, Autism Brain Net, Innovation and Value Initiative, Rare Disease Diversity Coalition, Cambridge Rare Disease Network, Breaking Down Barriers, Rare-X, Mencap, IndoUSRare, The World Orphan Drug Congress,  and Research America.