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£2 million US government funding may provide new treatment for rare genetic disease

Researcher at the University of Exeter and University of Maryland School of Medicine have been awarded $2.7 million (~£2 million) from the US government to fund a ground-breaking seven-year research programme to find new treatments for a rare childhood condition.

Dr Emma Baple and Professor Andrew Crosby are the Exeter leads of the research programme funded by the National Institutes of Health (NIH), which is giving hope for families across the world affected by ‘KPTN-associated neurodevelopmental disorder’. The team plans to discover treatments to prevent some of the health impacts of the condition which include autism, epilepsy which may be severe and difficult to treat, developmental delay and learning difficulties. The medical problems associated with the condition are thought likely to be related to the abnormally large head and brain size that is characteristic of the disorder.

Prof Crosby and Dr Baple identified and defined the genetic cause of the condition via their genomics research studies in the Amish communities in Ohio (USA). Amish children and adults with the disorder had been diagnosed with Autism, but the Exeter research team recognised that this was a distinct disorder new to medical science. They discovered that the condition is caused by alterations in the ‘KPTN’ gene which forms part of the ‘mTOR pathway’, a molecular process important for the way the brain grows and develops.

The Exeter team subsequently contacted Dr Peter Crino, Chair of the Department of Neurology at the University of Maryland School of Medicine, who is an internationally-renowned mTOR pathway expert specialising in developmental brain disorders to devise new therapies for KPTN-related disease that have been effective in other mTOR pathway disorders. He agreed to serve as co-applicant on the grant.

Dr Emma Baple said: “We’re delighted to receive this funding, which could make a huge difference to families affected by this condition across the world. We hope that our work will identify new treatments for the disorder that improve symptoms and may potentially stop certain medical problems such as epilepsy developing, if we can identify and treat patients affected by the disorder at the start of their lives.”

Professor Andrew Crosby said: “We’re excited to get started on this important study. It’s an example of how international genomic research studies may provide hope to families with specific rare diseases in the UK and worldwide, who may never otherwise have known the cause or potential treatment pathways for their condition.”

The application to the NIH was accompanied by a supporting statement from ‘The KTPN Alliance’ (https://kptnalliance.org/), a global community for sharing information about the health impacts of the disorder which provides invaluable support for families affected by the condition, and was co-founded by Dr Baple.  

KTPN Alliance parent co-founder Cara Abercrombie said: "As a parent, you want to feel like you’re doing all you can for your child. It’s been so difficult watching our daughter suffer from epilepsy. Finally, with this funding, and the promise offered by these brilliant researchers, we feel like we truly are doing all we can to help our daughter and, for the first time in many years, feel genuine hope she can have seizure relief and a better quality of life.”

Fellow KTPN parent co-founder David Freccia said: "This funding, and the teams' research, means the world to us and our family. Early research succeeded in identifying the specific gene and protein driving our daughter's disease. This helped us find a small, worldwide community of families impacted by KPTN syndrome, and better understand the disease. This week's grant will help push forward to examine treatment options that could improve quality of life for our daughter, her peers, and other families that may be impacted in the future. We feel hopeful, grateful, optimistic, and comforted by this work, which makes an enormous difference for our daughter and our family.”

The application was selected from a highly competitive pool of applicants for an award due to recommendation of the National Advisory Neurological Disorders and Stroke (NINDS) Council, an Institute within the National Institutes of Health (NIH). The award is given initially for a period of four years, after which, based on an administrative review, an additional project period of three years may be awarded.

Date: 18 November 2021