Targets for Epilepsy: From Genomic Studies to Gene Therapy

Epilepsy is a neurological condition marked by spontaneous seizures. Challenges in translating experimental epilepsy studies to clinical use include model validation, efficacy metrics, and long-term gene therapy safety concerns.¹ Nevertheless, identifying targets using genomic data offers crucial insights into epilepsy’s genetic foundation. This blog explores the potential of genes, such as SCN1A and TNKS, as therapeutic targets for epilepsy.

As one of the most common neurological diseases worldwide, affecting approximately 50 million people, epilepsy has a profound societal impact.² Currently, management primarily relies on antiseizure medicines and curative surgical procedures. However, an estimated 30-40% of epilepsy patients do not respond satisfactorily to seizure control with medication,³ and fewer than 1% of drug-resistant epilepsy patients are referred for surgery.⁴ This unmet need demands innovative solutions such as gene therapy, for personalized and more effective seizure control.

Gene therapy offers a solution to genetic disorders by repairing or replacing malfunctioning genes. Initial human trials of gene therapy commenced in the 1990s, and has shown promise in treating specific cancers,⁵ and neurological conditions, such as spinal muscular atrophy.⁶ Despite 70-80% of epilepsy cases attributed to one or more genetic factors,⁷ progress in gene therapy has been slow. Pinpointing the specific genetic mutations responsible for epilepsy remains challenging.

Understanding genetic targets identified through Whole-Genome Sequencing (WGS) and Genome-Wide Association Studies (GWAS) is a critical step towards the development of targeted gene therapy. Here we use Causaly to identify targets for epilepsy with genetic data.

With 180,000+ publications on epilepsy, the exponential growth of biomedical data renders target selection challenging. By machine-reading the literature, Causaly can accelerate this process by streamlining the identification and prioritization of relevant therapeutic targets.

Over 3,000 targets for epilepsy were instantly uncovered by Causaly. Close to 250 of these targets have been reported in GWAS or WGS studies. Of the 250 targets with associated GWAS data, 34 targets were reported in the GWAS catalog (Figure 1), while the rest came from GWAS studies published in other Causaly data sources. Two targets were selected based on the strength of evidence (SCN1A) and one reported recently (TNKS).

Gene therapy holds immense promise for revolutionizing epilepsy treatment. By shedding light on genetic mutations associated with epilepsy, genomic data can help accelerate the identification of promising therapeutic targets in drug discovery.