Taking on the Challenge of Dravet Syndrome
Dravet Syndrome is a severe, complex, lifelong disorder of the central nervous system, characterized by frequent, prolonged, and difficult-to-treat seizures, developmental delays, behavioral difficulties, motor/orthopedic issues, and problems eating and sleeping. Unfortunately, one fifth of patients with Dravet die before reaching adulthood. Typically, seizures begin in the first year of life of a previously healthy baby and are difficult to control even with multiple antiseizure medications. There are currently no approved therapies that address the full spectrum of symptoms associated with Dravet syndrome or the root cause of the disease.
The majority of Dravet syndrome cases are caused by loss-of-function mutations in the SCN1A gene, which reduce its function by 50%. This gene encodes the voltage-gated sodium channel type 1 alpha subunit (NaV1.1).
Our Experimental Therapy for Dravet Syndrome
ETX101 is a potential one-time, disease-modifying gene therapy for SCN1A+ Dravet syndrome that aims to eliminate or decrease seizure frequency, prevent onset and progression of neurodevelopmental symptoms, and enhance the quality of life of patients and families caring for them.
Gene regulation therapy with ETX101 uses an Adeno-associated Virus (AAV) vector that delivers instructions to increase activity of the patient’s own SCN1A gene, resulting in upregulation of sodium channels to healthy levels specifically within the affected cell type, GABAergic inhibitory neurons.
In preclinical studies1, a single dose of ETX101 dramatically reduced seizures and extended survival in a well-established mouse model of Dravet syndrome.
1 Young AN, Tanenhaus A, Chen M, McLaughlin J, Belle A, Li J, Lin W, Place K, Rodriguez D, White K, Kearney J, Tagliatela SM. A GABA-Selective AAV Vector-Based Approach to Up-Regulate Endogenous Scn1a Expression Reverses Key Phenotypes in a Mouse Model of Dravet Syndrome. Oral presentation at: American Society of Gene & Cell Therapy Annual Meeting; 2019 Apr 29 – May 2; Washington DC, US.
About Clinical Trials
Multiple studies must be conducted before an investigational therapy can be made available for patients; these studies are referred to as clinical trials. They are research studies conducted in human participants to test for safety, efficacy, dosing, and more. Clinical trials are regulated by the Food and Drug Administration (FDA) in the United States and by similar regulatory agencies worldwide, and they use trial data and other information to decide if a new product is safe and effective for use in routine medical care. Participating in a clinical study offers an opportunity to contribute to research that may advance the understanding of a disease or help get a new product approved, which can make a difference in the care of current and future patients.
Encoded is Conducting the Following Clinical Trials in Dravet Syndrome
ENVISION is a prospective natural history study (without gene therapy) designed to further define the seizure, neurodevelopmental, motor, and behavioral characteristics of SCN1A+ Dravet Syndrome in children who are aged 6 to 60 months (at the start of the study) and who have an SCN1A mutation. The study will examine these characteristics over two years using standardized assessments and will also explore the impact of the disease on parents/caregivers and health care resource utilization (HCRU).
The first clinical trial of ETX101 gene regulation therapy is planned to initiate in the second half of 2021.
If you locate a participating site that you are interested in, you or your physician may contact that site directly for more information.