Authors :
Presenting Author: Stéphane Auvin, MD, PhD – Service de Neurologie Pédiatrique, Hôpital Robert Debré, Paris, France
James Goss, PhD – STXBP1 Foundation; Charlene Son Rigby, - – STXBP1 Foundation; Deborah Bilder, MD – University of Utah, Salt Lake City; Clara Juandó-Prats, MScN, PhD – St. Michael’s Hospital and University of Toronto; Jacqueline Gofshteyn, MD – Encoded Therapeutics; Emma James, PhD – Encoded Therapeutics; Maria Candida Vila, PharmD, PhD – Encoded Therapeutics; Salvador Rico, MD, PhD – Encoded Therapeutics
Rationale:
STXBP1-DEE is a severe developmental and epileptic encephalopathy (DEE) with significant unmet need and no currently approved targeted treatments. Limited data exists describing the full range of symptoms and disease impact on children living with STXBP1-DEE and their families. We initiated STXBP1 ENGAGE to better understand the lived experiences of families and inform the design of clinical studies of disease-modifying therapies.
Methods:
Patient advocacy organizations shared a non-identifiable survey with people caring for individuals with STXBP1-DEE of all ages and from all five continents. In-depth interviews were conducted with 20 caregivers of children < eight years of age living with STXBP1-DEE from five countries (US, UK, ES, CA, and AU). While prompts and open-ended questions were used to facilitate the discussion, caregivers described experiences in their own words and preferred sequence. Interviews explored various topics to understand the STXBP1-DEE family journey.
Results:
A total of 199 parents responded to the survey. 138/199 (42%) people were diagnosed with STXBP1-DEE before age six years and 54 (27%) before age one year. In 70% (n=140) of cases, families first sought out a healthcare professional due to seizures, while remaining visits were prompted by developmental motor delays (n=87; 44%), communication delays (n=54; 27%), and floppiness or hypotonia (n=49; 25%). The most common seizure types in the first year of life were focal-onset motor (n=83; 54%), epileptic spasms (n=77; 50%), and myoclonic seizures (n=50; 32.3%). By the time of survey, most people with STXBP1-DEE had experienced communication delays (n=186; 94%), delays in key developmental motor milestones (n=185; 93%), and seizures (n=164; 82%). In-depth interviews revealed that despite emergence of disease signs in the first year, the average time to diagnosis was 19 months (range 5wk–5yr), with the largest obstacle being access to genetic testing. After diagnosis, two healthcare journeys emerged based on the presence and severity of seizures. Group One, experiencing seizures, faces frequent hospitalizations and healthcare encounters, and persistent seizure fear despite the use of multiple antiseizure medications. Group Two, without seizures, requires less urgent care but still requiring full-time care due to cognitive impairments. Transition between groups can occur over time based on changes in seizure profile. However, both groups face high disease impact on the whole family unit. The most desired aspects to be alleviated by a potential treatment were similarly reported in both portions of the study as control of seizures and ability to communicate basic needs.
Conclusions:
STXBP1-ENGAGE demonstrates that children living with STXBP1-DEE experience numerous symptoms beyond seizures. Despite substantial phenotypic heterogeneity, STXBP1 has a significant negative impact on the daily lives of children, caregivers, and family members highlighting the need for therapies that address the full spectrum of seizure, cognitive, behavioral, and motor symptoms.
Funding: This study was funded by Encoded Therapeutics.