Centre for Genomic & Experimental Medicine
Centre for Genomic & Experimental Medicine

Drug repurposing for a rare genetic neurodevelopmental disorder

Supervisor - Professor Cathy Abbott

About the Project:

This project is one of 17 four year PhD Studentships funded by Medical Research Scotland (https://www.medicalresearchscotland.org.uk) to be delivered jointly by the named University and External Partner Organisation (EPO). The Studentship will provide the first-class academic and additional training provided by the EPO needed to equip the successful candidate for a science career in an increasingly competitive market.

"Developing treatments for rare disease: drug repurposing and discovery for a rare genetic epileptic encephalopathy" to be delivered by the University of Edinburgh [Supervisors: Professor Cathy Abbott (Centre for Genomic and Experimental Medicine, University of Edinburgh) and Professor Neil Carragher (Cancer Research UK Edinburgh Centre, University of Edinburgh)] and Healx Ltd (https://healx.io/) [External Partner Organisation supervisor: Dr Tim Guilliams].

Early onset epilepsy is usually severe and associated with delays in development, limiting the child’s ability to learn. Many cases of these neurodevelopmental disorders are now known to be caused by rare de novo mutations in specific genes. Most children with mutations in the gene EEF1A2, which encodes a neuronal-specific translation elongation factor called eEF1A2, will have multiple daily seizures. Many never learn to talk, have ataxia and dyskinesias and some experience a degenerative course. Since the seizures are often intractable, effective treatments are badly needed. Through our website and outreach work, we have been able to connect families all over the world. The objective of this studentship is to provide a broad training in the challenges and development of therapies for rare disease therapy, and ultimately to find a drug(s) that could ameliorate the clinical condition of individuals with mutations in EEF1A2 by altering the levels of the protein. This might involve better control of seizures, improved outcomes in terms of neurodevelopment or the prevention or delay of any degenerative phenotypes.

The student appointed to this project will receive a broad training in therapy for rare disease, and will be able to take advantage of the laboratory tools we have developed, including animal models which mimic the human disease, to identify new therapies for children with mutations in EEF1A2. To do this they will test libraries of repurposed drugs and novel small molecules in cultured cells for their ability to alter the expression of eEF1A2, and ultimately test the best candidates in our novel mouse lines which recapitulate specific clinical mutations. Some of these drugs are repurposed- they are already being used to treat other more common conditions, with known safety and delivery profiles. This project is being conducted in partnership with Healx, experts in the use of artificial intelligence for rare disease.  


Enquiries should be sent by email to Professor Cathy Abbott: C.Abbott@ed.ac.uk


Applicants must have obtained, or expect to obtain, a first or 2.1 UK honours degree, or equivalent for degrees obtained outside the UK, in a relevant subject

Applications are welcome from UK nationals as well as EU nationals that hold UK settled or pre-settled status.

Applicants should send a CV, the contact details of 2 referees (including email addresses) and a covering letter explaining why they would be suited to this project, by email to Professor Cathy Abbott: C.Abbott@ed.ac.uk

Please note, your application may be shared with the funders of this PhD Studentship, Medical Research Scotland and Healx Ltd.

Interviews are expected to take place approximately 4 weeks after the closing date for applications. Interviews may be conducted by video conference.

It is anticipated that the PhD Studentship will start 12 September 2022.