Six patient advocacy groups collaborate to co-fund a single-center observational study of seizure types in rare genetic epilepsies
News Release 17-Sep-2024
Six patient advocacy groups collaborate to co-fund a single-center observational study of seizure types in rare genetic epilepsies
SRF (SYNGAP1), RSRT (Rett), CACNA1A, STXBP1, Loulou (CDKL5), & KCNQ2 Cure (KCNQ2) collaborate to support Dr. Devinsky’s research for clinical trial readiness.
Syngap Research Fund
Six rare disease organizations support the research of Dr. Orrin Devinsky at NYU Grossman School of Medicine
Credit: SynGAP Research Fund, Rett Syndrome Research Trust, CACNA1A Foundation, STXBP1 Foundation, Loulou Foundation, KCNQ2 Cure Alliance, Orrin Devinsky, MD, and NYU Grossman School of Medicine
Mill Valley, CA – September 17, 2024 – The SynGAP Research Fund 501(c)(3), dba Cure SYNGAP1, alongside Rett Syndrome Research Trust, CACNA1A Foundation, STXBP1 Foundation, Loulou Foundation and KCNQ2 Cure Alliance, announced a $275,000 grant to Orrin Devinsky, MD, of NYU Grossman School of Medicine, to improve the diagnostic accuracy of parents/caregivers in classifying paroxysmal events as seizures versus non-seizures, and classifying seizure types. This should fulfill two key goals: first educate clinicians and parents/caregivers to more accurately distinguish epileptic from non-epileptic events and classify seizures, and second improve the chances of successful clinical trials for medications or genetic precision therapies.
Why We Supported This Project
Co-funded by multiple organizations, this grant is a strong example of collaboration across the rare disease community. By joining forces, these organizations are not only advancing research and treatment options but also demonstrating the strength and impact of collective action in the fight against Developmental Epileptic Encephalopathies (DEEs). This initiative promises to significantly improve clinical outcomes and enhance the quality of life for countless families affected by rare genetic epilepsies.
What the Organizations Are Saying
“We are thrilled to receive this grant from many rare neurogenetic disease foundations to support this project that will enhance parents’ abilities to accurately distinguish seizures from non-seizures and classify the type of seizure,” said Dr. Devinsky of NYU Grossman School of Medicine. “This can greatly increase the signal to noise and enhance the development of therapies for these devastating disorders.”
According to Ana Mingorance, PhD, Chief Development Officer of the Loulou Foundation, “A problem with epilepsy trials is that regulatory agencies ask for caregivers to be the reporters for seizures, not EEG or wearable detectors. And some seizures are hard to detect, because they might look like a twitch or a movement, but they are in fact seizures. The study at NYU is very important for the entire field because it addresses the observer reliability problem not by trying to change regulatory standards, which could take us decades, but by helping caregivers be more reliable as seizure reporters. This will help us de-risk clinical trials for DEEs in the immediate future.”
Charlene Son Rigby, President of the STXBP1 Foundation, explained, “Seizures are a prominent and debilitating symptom in STXBP1-related disorder. The ability for patients and physicians to quickly and accurately identify seizures is critical for timely patient care. Infantile spasms are a common seizure type in STXBP1, and due to their subtlety are challenging to recognize, yet they require urgent medical attention. This important study aims to advance the ability of both caregivers and providers to identify and accurately classify seizures.”
“Misdiagnosis of seizures in children with rare genetic epilepsies can lead to significant challenges. Inaccurate classification can result in inappropriate treatment and hinder research efforts,” emphasized Marissa LaDue, MPH, Program Manager of the KCNQ2 Cure Alliance. “Accurately classifying seizures in KCNQ2 is crucial for effective treatment since KCNQ2 mutations can cause either too much or too little potassium in the brain, affecting treatment options. Tailored treatment plans are essential due to the unique nature of each KCNQ2 case.”
Monica Coenraads, CEO of the Rett Syndrome Research Trust says they are pleased to participate in this study because ”one of the most common questions asked by parents of children with Rett is whether the movements they are seeing in their children are seizures or a movement disorder or something else. Assisting families to recognize and properly classify seizures is critical.”
Lisa Manaster, Co-founder and President of the CACNA1A Foundation, Inc., remarked, “Pathogenic mutations in the CACNA1A gene cause various types of paroxysmal events—sudden episodes that happen from time to time—including seizures, hemiplegic migraines (stroke-like episodes), and ataxia attacks (loss of balance accompanied by nausea and vomiting.) Even experts have trouble differentiating between these events. This study is crucial for the CACNA1A community, as it aims to enhance diagnostic accuracy in distinguishing between seizures and non-seizure events, ultimately improving treatment options and quality of life for patients and their families.”
Mike Graglia, Co-founder and Managing Director of the SynGAP Research Fund, observes, “The seizure progression in SYNGAP1-Related Disorders (SRD) is gradual but treacherous. By age two most of our patients are experiencing large numbers of absence seizures often missed by clinicians and families alike. After progressing to Myoclonic seizures, we sometimes see convulsive seizures. Then, somewhere between age 2 and adulthood with no rhyme or reason, our patients present with drop seizures. EEGs and clinical presentations rarely agree. This project is essential for both our parents and clinicians working with SRD.”
Family Donations Make Progress Possible
Virginie McNamar, Partnerships Director for SRF, says, “Every dollar Patient Advocacy Groups raised comes from families. By combining these funds into one collaboration we are able to maximize the impact of these precious funds. We look forward to this project helping all the disorders involved improve their clinical trial readiness and to the insights Dr. Devinsky’s team will learn from working on multiple diseases at once.” She continues, “The groups involved in this project are some of the very best. It is a pleasure to work with all of them.”
About CDKL5 Deficiency Disorder
CDKL5 deficiency disorder (CDD) is a serious and rare genetic disorder that is caused by a mutation of the cyclin dependent kinase like 5 (CDKL5) gene, located on the X chromosome. CDD is characterized by early onset, difficult to control seizures and severe neurodevelopmental impairment. One out of 40,000 babies are born with CDD. The drug ganaxolone (Ztalmy) is approved for the management of seizures in CDD, but there are no approved disease-modifying therapies for people living with CDD.
About the Loulou Foundation
The Loulou Foundation is a private non-profit organization founded in 2015 to support the development of effective therapeutics and eventual cures for CDD. Through robust grant and directed research programs, the Foundation provides tools and resources to basic and clinical scientists to enable the development of disease-modifying therapeutics for CDD. These programs include support for pre-clinical, translational, and clinical research into basic CDKL5 biology, CDD disease mechanisms, and the proof-of- concept studies for gene therapy and genome modifying therapeutics.
About STXBP1-Related Disorder
STXBP1-RD is a rare neurodevelopmental disorder caused by changes in the STXBP1 gene. The estimated incidence rate for STXBP1-RD is ~1:30,000, and STXBP1 was recently identified as one of the five most common genes for epileptic encephalopathies and related neurodevelopmental disorders. Seizures impact 85 – 90% of patients, and may present as early as the first day of life. Common seizure types include neonatal seizures, infantile spasms, tonic, and clonic seizures. Patients may also present with a broad range of symptoms including global delays, intellectual disability, speech and communication issues, hypotonia, spasticity, and behavior issues.
About STXBP1 Foundation
STXBP1 Foundation is dedicated to finding a cure for STXBP1-Related Disorders while improving the lives of our patients and families. Founded in 2017, STXBP1 Foundation is a parent-led advocacy organization. STXBP1 Disorder is a rare epileptic and neurodevelopmental disorder caused by changes in the STXBP1 gene. With an incidence of approximately 1 in 30,000 live births, STXBP1 Disorder is one of the most common genetic causes of epilepsy. For more information, contact info@stxbp1disorders.org and visit https://www.stxbp1disorders.org/
About Rett Syndrome
Rett syndrome is a rare genetic neurodevelopmental disorder caused by random mutations in the MECP2 gene on the X chromosome. The disorder predominantly affects girls but can also rarely affect boys. Symptoms typically become apparent between the ages of 12 to 18 months. Rett syndrome is devastating as it deprives toddlers of speech, hand use, and normal movement often including the ability to walk. As childhood progresses the disorder brings anxiety, seizures, tremors, breathing difficulties, and severe gastrointestinal issues. While their bodies suffer, it is believed that their cognitive abilities remain largely intact. Although most children survive to adulthood, they require total round-the-clock care.
About The Rett Syndrome Research Trust
RSRT is the patient advocacy organization working to cure Rett syndrome. As the largest funder of Rett syndrome research worldwide, RSRT has played a vital role in initiating and evolving the trajectory of progress toward a cure. All genetic therapies in development by biopharmaceutical companies have leveraged discoveries and resources made possible by RSRT. Learn more at reverserett.org.
About KCNQ2-Related Disorders
KCNQ2 is a rare genetic disorder that primarily affects the brain. It is caused by mutations in the KCNQ2 gene, which provides instructions for making potassium channels in the brain. These channels help regulate the electrical activity of brain cells. The most common symptom of KCNQ2 is seizures, which typically begin within the first week of life. Other key features of KCNQ2 include developmental delays, cognitive Impairment, low muscle tone (hypotonia), increased muscle tone in their limbs (spasticity), or features of autism spectrum disorder.
About the KCNQ2 Cure Alliance (KCA)
The KCNQ2 Cure Alliance is a non-profit organization on a mission to find a cure for KCNQ2-related disorders. Founded by four dedicated parents, it started as a support group and has grown into a thriving 501(c)3 organization. Today, it offers invaluable support and resources to families affected by KCNQ2 while funding research projects that aim to unlock the mysteries of this rare disorder and develop innovative treatments.
About CACNA1A-related Disorders
CACNA1A is a rare neurodevelopmental disorder caused by changes in the CACNA1A gene, a calcium ion channel gene highly expressed in the central nervous system and cerebellum. These changes disrupt electrical signals in the brain, leading to various neurological issues, including global developmental delays, intellectual disability, autism spectrum disorder, and speech and language disorders, as well as epilepsy, ataxia (balance and coordination difficulties), hemiplegic migraines (stroke-like episodes that result in coma, brain swelling, and skill regression), and eye movement disorders.
About the CACNA1A Foundation
The CACNA1A Foundation, a 501(c)(3) non-profit organization, was founded in 2020 by parents of children with CACNA1A-related disorders. Their goal is to improve the lives of individuals affected by this rare neurodevelopmental genetic disease through advancing research, supporting families, and raising awareness. The mission of the Foundation is to find specific treatments and a cure by building a collaborative network of patients, families, clinicians, and scientists to accelerate the understanding, diagnosis, and treatment of CACNA1A-related diseases. For more information, please contact info@cacna1a.org and visit www.cacna1a.org
About SYNGAP1-Related Disorder (SRD)
SYNGAP1-Related Disorders (ICD-10 F78.A1; ICD-11 LD90.Y) is a rare genetic disorder caused by variants on the SYNGAP1 gene that reduce SynGAP protein levels. SRF has identified over 1,454 patients to date, and the number grows weekly. This protein acts as a regulator in the synapses (where neurons communicate with each other). When SynGAP 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 SynGAP patients.
Symptoms of SYNGAP1 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 (SRF)
The mission of the SynGAP Research Fund (SRF) 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, and families created sister organizations for SRF in the UK in 2020, in Europe (Netherlands) in 2022, and in Latin America (Colombia) in 2023.
Completely family-led, SRF is the largest non-government funder of SynGAP research having committed over $6 million in grants. The founders cover operational costs, ensuring donations fund science & patient-related programs. 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.
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, and The World Orphan Drug Congress.
