By Syngapian grandfather & SRF volunteer, Ed Gabler

SynGAP Research Fund’s scientific conference last month was monumental. Sixteen speakers– doctors, scientists, researchers–presented a wide variety of information to a packed room of other researchers and many, many SRF families. To say that the information was, and is, important would be a gross understatement. To say that the sheer number of brilliant minds, together in the same room, talking about treatments for our kids was overwhelming and extremely encouraging would be accurate.

Below are the speakers and links to their video presentations. The brief accompanying statements do not do their words justice. Watching the videos will be well worth your time.

Session 1: The State of Rare Disease Gene Based Trials

Moderator: Ingrid Scheffer, MBBS, PhD, University of Melbourne

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TANGO Precision Medicine Platform

Ed Kaye, MD, CEO & Director, Stoke Therapeutics

The success in early studies of treatments for Dravet Syndrome may correlate to possible future treatments for SYNGAP1.

View Dr. Kaye's slides here. ‍

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"N of 1s" and Their Place in the Rare Disease Trial Ecosystem

Timothy Yu, MD, PhD, Boston Children’s Hospital and Harvard Medical School

N=1 interventions are studies based on treatment of a single patient rather than a large group. What considerations are discussed before approaching this type of study?

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mRNA Amplifier Technology for SYNGAP1

Jeff Coller, PhD, Johns Hopkins University 

This presentation discusses some of the mRNA research that is going on to develop technology to enhance a specific mRNA’s translation.

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Session 1 Moderated Q&A 

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Session 2: Defining the SYNGAP1 Clinical Spectrum: Identifying Outcomes for Preclinical and Clinical Trials

Moderator: Ingo Helbig, MD, Children’s Hospital of Philadelphia and University of Pennsylvania Perelman School of Medicine 

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SYNGAP1 Clinical Spectrum from Ciitizen Database

Kimberly Wiltrout, MD, Boston Children’s Hospital and Harvard Medical School

The first presentation of Session 2 presented phenotypic data (symptoms, characteristics) of up to 150 SYNGAP1 Patients registered in Ciitizen.‍

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SYNGAP1 Clinical Spectrum in Adults    

Danielle Andrade, MD, MSc, University of Toronto

Phenotypic data of and how SYNGAP1 presents in adults was presented based on 14 adult (>18 yo) Syngapians.

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Sleep and SYNGAP1

Constance Smith-Hicks, MD, PhD, Kennedy Krieger Institute and Johns Hopkins University
Sleep is critical for many physiological functions. Findings of studies into the relationship between SYNGAP1 and quality and quantity of sleep were shown.

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Measuring Communication Ability in Clinical Trials: A Caregiver-Centered Approach

Bryce B. Reeve, PhD, Duke University School of Medicine

To prove that future drugs help our kids, we first must measure baselines (such as in communication) so we can show improvement.

View Dr. Reeve's slides here.

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Session 3: Key Efforts within SynGAP Pre-clinical Models

Moderator: Rick Huganir, PhD, Johns Hopkins University

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SynGAP Isoforms

Gavin Rumbaugh, PhD, Scripps Research Institute

The SYNGAP1 gene encodes multiple, different proteins and helps to organize the brain. Isoforms introduced into animal models are being studied to try to understand  new functions of the SYNGAP1 gene. Understanding how  it works is key to understanding how to fix it.

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Rat Model of SYNGAP1

Sally Till, PhD, The University of Edinburgh

In addition to mouse models, rat models can be a complementary means to study SYNGAP1 on our road to a cure. Some data from studies of SynGAP rats were presented.

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Epigenetic Regulation of SYNGAP1-Related Intellectual Disability

Elizabeth A. Heller, PhD, University of Pennsylvania Perelman School of Medicine    

An approach using the CRISPR tool to change the SYNGAP1 gene’s expression as used with wild type mice and Syngap model mice was shown.

View Dr. Heller's slides here.

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Moderated Q&A

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Session 4: Designing a Trial

Moderator: Annapurna Poduri, MD, MPH, Boston Children’s Hospital and Harvard Medical School

Epilepsy Trial Methodologies

Jacqueline French, MD, NYU Langone School of Medicine

In 2022, there were more trials in pediatric rare diseases than in adults. This presentation discusses different considerations when setting up these trials.

View Dr. French's slides here.

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NIH Funding Mechanisms

Vicky Whittemore, PhD, National Institute of Neurological Disorders and Stroke, NIH

NIH funding into SYNGAP1 was $500K from 2012 - 2021; in 2022, funding was 5.6 million! SRF has been raising money and approving grants to allow researchers the opportunity to develop preliminary data to include in grant applications to NIH to obtain additional funding and continue their research.

View Dr. Whittemore's slides here.

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Breakout Sessions & Closing Remarks

Several breakout sessions concluded the day. Summaries were provided for 1) Pre-clinical, 2) End Points, 3) Barriers before SRF managing director Mike Graglia provided some parting comments. 

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When the microphone was turned off, the meeting may have ended, but the work is continuing. Much of the science was possibly impossible to decipher, but it’s still important to watch and listen to the videos. The lineup was impressive. The breadth of research happening is amazing. The wait will be long, but we gained incredible hope and impatient optimism for our kids’ future. 

SRF is at the forefront of this science, and if you’re reading this, you’re part of SRF in one form or another. Mike said it very succinctly:  “There’s thousands of kids out there…. It’s our job to build this house, make it bigger, to bring them into it and to make it better! That’s why we’re here.”

Also in Mike’s own words, “In spite of everything we’ve achieved, it’s nothing compared to what we’re about to get done!”

Let’s work together to keep the momentum going throughout 2023!