Trial Information

Potential EEG Biomarkers and Antiepileptogenic Strategies for Epilepsy in TSC

Current therapeutic approaches for epilepsy primarily represent symptomatic treatments that
suppress seizures, but have not been demonstrated to prevent epilepsy or modify disease
progression. In recent years, there have been tremendous interest and effort by basic
scientists and clinicians in epilepsy in developing disease-modifying or "antiepileptogenic"
therapies. However, these efforts are hindered by a couple significant limitations: 1)
difficulty in identifying an appropriate high-risk patient population in which a
preventative approach is feasible and justifiable, and 2) lack of appropriate drug targets
with antiepileptogenic properties. Tuberous Sclerosis Complex (TSC) is one of the most
common genetic causes of epilepsy and a subset of TSC patients may represent a rational,
feasible population to target with an antiepileptogenic approach for several reasons. First
of all, some patients are diagnosed with TSC at a young age before the onset of epilepsy due
to non-neurological findings - thus, it is feasible to identify these patients and initiate
a potential antiepileptogenic treatment at an early stage of epileptogenesis. Second, these
patients are at high risk for developing epilepsy (~80%) in the future, including infantile
spasms (~35%), a particularly devastating type of childhood epilepsy with a poor prognosis -
thus, initiating a therapy with potential side effects in a pre-symptomatic stage can likely
be justified in TSC patients. Finally, the identification of the mTOR pathway in the
pathophysiology of TSC suggests that mTOR inhibitors could have antiepileptogenic properties
in TSC, as already supported by pre-clinical animal studies - thus, a rational
mechanistically-based treatment potentially already exists and can be readily tested in TSC
patients. However, there may be significant risks and side effects of mTOR inhibitors,
especially during early childhood, such as chronic immunosuppression and theoretical effects
on learning, growth, and development. Thus, before initiating an antiepileptogenic drug
trial in TSC patients, it would be beneficial to obtain further evidence to optimize the
selection criteria and treatment paradigms to maximize efficacy and minimize side effects of
mTOR inhibitors.

The aim of this clinical trial is to determine whether EEGs during infancy is a reliable
biomarker to identify TSC patients that will develop infantile spasms/epilepsy in the near
future and thus are appropriate candidates for an antiepileptogenic drug trial.