Development of treatments for skeletal muscle excitability disorders

Summary

This studentship offers a unique opportunity to participate in an industry collaboration that aims to develop novel small molecule drugs targeting the skeletal muscle specific chloride ion channel (ClC-1).

This novel treatment approach holds significant therapeutic potential for treating a diverse set of skeletal muscle disorders, including myasthenia gravis and spinal muscular atrophy. By increasing the excitability of muscle fibres, small molecule inhibitors of ClC-1 activity can restore neuromuscular transmission, increase strength, and improve movement.

However, while reducing ClC-1 activity can enhance muscle excitability, potentially benefiting patients, there is a risk that excessive ClC-1 inhibition induces skeletal muscle hyperexcitability with ensuing myotonia.

Project aims

In this studentship small molecule inhibitors with highly specific biophysical properties will be explored that reduce the risk of myotonia.

The student will gain desirable skills including advanced electrophysiology techniques and computer modeling. The project involves rational design and subsequent testing of novel drug candidates that aim to modify ClC-1 function.

This will be done through computational modeling to predict suitable drug properties followed by confirmation using electrophysiological testing of drug candidates in advanced skeletal muscle preparations.

This is an unusual opportunity to contribute to an entire drug development program, from foundational electrophysiological research and computer modeling to laboratory testing, ultimately progressing to clinical trials.

This partnership between academia and industry enables the student to significantly impact the treatment of skeletal muscle disorders while gaining highly valuable skills and experience in research and drug development. 

Contact details

Dr James Fraser - jaf21@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

• PhD