Topical mTOR inhibitor therapy in tuberous sclerosis

Sergiusz Jóźwiak, Krzysztof Sadowski, Katarzyna Kotulska, Robert A. Schwartz.  Topical use of mTOR inhibitors in tuberous sclerosis complex – a comprehensive review of the literature.  Pediatric Neurology. In press.

Abstract

Background

Tuberous sclerosis complex (TSC) is a genetically determined multisystem disorder that may affect almost any human organ. The discovery of the mammalian target of rapamycin (mTOR) pathway and its involvement in TSC-related pathology has led to the introduction of mTOR inhibitors into clinical practice. Topical administration of mTOR inhibitors for skin lesions related to TSC may represent a reasonable alternative for more invasive procedures.

A growing number of patients have been described exhibiting positive therapeutic effects from the topical administration of mTOR inhibitors.

The aim of this review is to systematically analyze available literature on the use of topical mTOR inhibitors to treat dermatological lesions related to TSC.

Results

A comprehensive review of PubMed, Medscape and Cochrane databases between 1995 and 2015 was performed to identify available studies describing topical use of mTOR inhibitors in TSC patients.

In most published cases topical mTOR inhibitor application proved to be effective in the treatment of skin lesions related to TSC. Facial angiofibromas were the target lesions in most cases. Few studies reported clinical improvement of hypomelanotic macules.

mTOR inhibitors directly address the molecular defect related to TSC manifestations.

Conclusions

Currently available clinical data reviewed in this study suggest that topical application of mTOR inhibitors represents a significant progress in the treatment of facial angiofibromas associated with TSC. However, double-blinded studies on larger groups of patients are necessary.