Emerging treatments and therapeutic targets for tuberous sclerosis complex in children

ABSTRACT

Introduction: Tuberous sclerosis complex (TSC) is a genetic disease affecting 1:6000 newborns. It is a multisystem disease caused by overactivation of mechanistic target of rapamycin (mTOR) pathway and associated with the development of many benign tumors in different organs (e.g. brain, skin, kidney, lungs, heart) and comorbidities including epilepsy, cognitive impairment, neuropsychiatric disorders. In recent years, some new therapeutic agents and strategies have emerged for TSC.

Areas covered: In the article, authors discuss the results of recent studies particularly on epilepsy management including preventive antiepileptic treatment in TSC infants, current studies on cannabidiol, and an increasing role of mTOR inhibitors (sirolimus, everolimus) in the treatment of many TSC manifestations.

Expert opinion: Recent years and studies resulted in significant progress in the therapy of TSC. Prevention of epilepsy in TSC children with subsequent improvement of cognitive outcome is currently possible. The question about the duration of preventive treatment in children who did not experience seizures will still be open. Considering the increasing role of mTOR inhibitors, the possibility of not only therapeutic but also preventive role of these drugs for TSC manifestations may be a question for future research.

KEYWORDS:

• Cannabidiol
• epilepsy
• mTOR
• mTOR inhibitor
• prevention
• therapy
• treatment
• tuberous sclerosis complex

Article highlights

• Early diagnosis of tuberous sclerosis and prevention of epilepsy with subsequent improvement of neurocognitive outcome is now possible.

• Cannabidiol is a new therapeutic option for TSC.

• Considering an antitumor property of cannabis, a potential role of cannabidiol in the management of TSC-related tumors may be interesting for future studies.

• mTOR inhibitors play an important role in the management of many different TSC manifestations and the question of the possible preventive role of mTOR inhibitors in TSC is emerging.

• This box summarizes key points contained in the article.

Declaration of interest

S Jozwiak was supported by Novartis Pharmaceuticals in the EXIST-1 and EXIST-2 studies. Both authors were supported by the European Union’s Research and Innovation funding program for 2007–2013 and the Polish Ministerial Funds for science within EPISTOP project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was partially funded by the 7th Framework of European Commission within the Largescale integrating project EPISTOP (Proposal No: 602391-2), The Polish Ministerial funds for science (years 2013-2019) for the implementation of international co-financed project and the grant EPIMARKER of the Polish National Center for Research and Development (No STRATEGMED3/306306/4/2016).