Launch of Clinical Trial to Investigate the Efficacy on Neurocognition and Behaviour of Everolimus in Children and Adolescents with PTEN Mutations

June 2017


The Boston Children's Hospital, Cleveland Clinic and Stanford University Medical Center, as part of the Developmental Synaptopathies Consortium (DSC), have launched their first clinical trial to investigate a potential treatment for individuals with PTEN Hamartoma Tumour Syndrome (PHTS). PHTS is a rare genetic syndrome that results from mutations in the PTEN gene. Symptoms of PHTS can be varied and may include macrocephaly (large head size), overgrowth of tissues, and an increased risk of cancers, along with an increased prevalence of autism, and neurocognitive delays. The trial is focused on trying to improve the neurocognitive function of children and adolescents with PHTS, by examining the safety and efficacy of a promising drug called everolimus.

The PTEN Research Foundation, which was established in early 2017 is pleased to be co-funding this trial, in conjunction with the National Institutes of Health (NIH), and the pharmaceutical company providing the drug. The mission of the PTEN Research Foundation is to accelerate medical research to help develop a therapy for PHTS.

As a supporter of the trial, the Foundation is proud to be working in partnership with leading clinical teams in the field of PTEN and PHTS research.

Background to the Trial

This trial assesses a key area of need for targeted pharmacology in rare neurogenetic populations and a subset of individuals with Autism Spectrum Disorder (ASD).   

PHTS is a genetic syndrome that results from mutations in the PTEN gene. Individuals with PHTS often experience a variety of syndrome-specific manifestations such as skin lesions, macrocephaly (large head size), overgrowth of tissues, and increased risk for cancers. There is also a high prevalence of autism, intellectual disability, and other neurocognitive deficits in PHTS patients.

This trial aims to examine the safety and efficacy of a promising drug called everolimus. Everolimus is a drug in the kinase inhibitor family that is utilized in the treatment of cancers by stopping cancer cells from reproducing and by decreasing blood supply to the cancer cells. Everolimus acts specifically as an mTOR inhibitor and targets biochemical pathways regulated by PTEN.

PTEN associated pathways are crucial to ongoing brain function. Mutation in the PTEN gene causes dysregulation of these important biochemical networks. Thus, if these pathways are normalised, the result may be improved brain function in individuals with PHTS.

About the Trial and Potential Impact

This trial addresses a key area of interest: pharmacological treatments of a well-defined subgroup with autism. PTEN gene mutations are associated with a spectrum of clinical disorders and a high incidence of autism symptomatology and neurocognitive disorders. Neurocognitive and neurobehavioral deficits are associated with very high morbidity, health care cost, and impact on the quality of life of individuals with PHTS and their families. Currently there are no approved agents for the treatment of these neurocognitive and neurodevelopmental deficits in PHTS.

Through this trial, we aim to elucidate potential for everolimus to influence the neurocognitive outcomes of 40 participants with PTEN mutations. In assessing the safety and efficacy of everolimus in this population, we hope to advise further trials of mTOR inhibitor utility in improving neurocognition in autism related disorders.

Background to the PTEN Research Foundation

The PTEN Research Foundation was launched in early 2017 to accelerate research that could lead to a therapy for PHTS (PTEN Hamartoma Tumour Syndrome).

By accelerating research and building networks and partnerships, we aim to stimulate the development and adoption of therapies for PHTS patients. We fund academic and clinical research projects, as well as provide support for building networks between clinicians, researchers, corporate partners and patients.

Focusing on translational medicine is a key area of interest for the PTEN Research Foundation. The Foundation’s core focus is to fund projects that will identify medicines that have the potential to reverse the impact that a PTEN gene mutation has on the cells and tissues and thereby alleviate, reverse or prevent the manifestations of PHTS.

Alongside funding for clinical trials, the Foundation will also support longitudinal studies to increase the understanding on the natural history of PHTS, as well as basic and preclinical scientific research with the aim to increase mechanistic understanding of the impact of PTEN mutation in the context of PHTS, and to test treatments that complement clinical research efforts.

The Foundation is based in London and has a global scope and remit; this is particularly important in the case of a rare disease such as PHTS, where the researchers, clinicians and patients may be geographically spread.

Additional Information for Patients

For more information about the Developmental Synaptopathies Consortium and this trial, please feel free to visit Please also note that participants may apply for funding to assist with travel expenses.

Information about this trial is also available here .