STXBP1 Clinical Outcome Measures & Biomarker Consortium (S-COMB)

What are the Objectives?

The Consortium has 4 primary objectives:

Identify clinical outcome measures useful for the STXBP1 community

The Consortium will help develop, choose, and/or modify existing clinical outcome measures that would be acceptable to FDA and EMA regulatory bodies as evidence of drug efficacy. These measurements should address demonstrable concerns affecting the STXBP1 patient population, such as communication, cognition, seizures, gross motor skills, fine motor skills, and general QOL/independence. They should be able to be quantifiable, implemented in a similar manner regardless of clinic site, and should consist of tests/measurements that do not place undue burden on the patient or caregiver.

Provide guidance to STXBP1 natural history studies

The Consortium will provide guidance and expert advice to the pre-competitive, prospective STARR natural history study being conducted in North America and the European STXBP1 Consoritum (ESCO) natural history study scheduled to begin enrolling participants in 2024. The goal of these studies is to generate longitudinal and/or aged cohort data to define a trajectory of symptoms and allow identification of a Minimal Clinical Important Difference in clinical domains that could be used as a basis for future drug approvals (e.g. as per a Multi Domain Responder Index).

Identify STXBP1-specific biomarkers

Disease-specific biomarkers can be very helpful in identifying patient populations for clinical trials, screening potential drug candidates, and monitoring patient responses to a therapeutic. Biomarkers could prove especially useful for STXBP1 disorder, which demonstrates a wide heterogeneity of clinical symptoms. Ideal biomarkers should be readily quantifiable, relatively economical, and correlate with a clinical outcome assessment. Potential biomarkers include electrophysiological (EEG), imaging (magnetic resonance spectroscopy), functional (eye tracking, pupillary light reflex), and biochemical (transcriptomics, proteomics, metabolomics).

Assure availability of preclinical models

Preclinical STXBP1 models are used by academic and translational researchers and pharma. These include cell lines, such as patient-derived iPSCs, and animal models, such as a humanized mouse model. Sharing of such resources are often complicated by institutional regulations and intellectual property concerns. The COMB will work towards addressing these concerns including developing additional models, encompassing specific mutation types or other species as may be warranted.