Case study: Repurposing of PI3K pathway modulators for PHTS
Introduction
PTEN Research partnered with two leading drug discovery Contract Research Organisations (CROs) to investigate whether existing medicines can be repurposed to treat PHTS. This approach offers a faster and lower risk path to potential PHTS clinical trials because these drugs already have significant data available and some have been tested for safety in humans.
Key facts
Project title: Preclinical Repurposing of PI3K Pathway Modulators for PHTS
Type of study: Preclinical - PHTS model development and testing to support drug repurposing
Contract Research Organisations (CROs):
Evotec – headquarters in Hamburg, Germany
Charles River Laboratories – headquarters in Wilmington, MA, USA
Project start: October 2020 Completed: Q1 2026
Project goals
The research teams created specialised laboratory non-human models to replicate the features of PHTS to test how different drugs affect specific problems experienced by people with PHTS. Evotec focused on models related to developmental delay and autism, while Charles River Laboratories developed models for vascular anomalies (abnormal blood vessels) and tissue overgrowth.
Project overview
The teams tested existing medicines that target an important pathway in our cells, the PI3K/AKT/mTOR pathway, which is known to be affected by PTEN variants that cause PHTS, as well as other important cellular pathways.
These research activities are managed by joint committees led by PTEN Research, scientists from the partner companies, and independent experts, with oversight from the PTEN Research board of Trustees.
Outcomes
Beyond identifying drugs that could move forward to possible future clinical trials, this research helps us understand how PTEN variants impact normal cell signalling. By studying these models, we are learning which pathways are most important for the different symptoms of PHTS, such as developmental delays, autism features, vascular problems, and tissue overgrowth. This knowledge is crucial for developing better, more targeted treatments in the future.
These projects have been completed. The following scientific publication has resulted from the work with Evotec:
Repurposing drugs for treating the neurobehavioral manifestations of PTEN hamartoma tumour syndrome.
A similar publication summarising the work with Charles River Laboratories is in preparation.
More information about the CROs can be found on their corporate websites.
