New Experimental Medicine group looks at excitability in brain, muscle and peripheral nerve

'We currently focus on measuring excitability of neurons and muscles cells, to develop drugs in neurology, psychiatry and pain management,' says Associate Research Director Dr Jules Heuberger, who leads the new group. Excitability is the 'willingness' of nerve cells to transmit stimuli. In some disorders, an abnormal excitability has been demonstrated. Most types of epilepsy, for example, are characterised by increased excitability of the brain, while patients with major depressive disorder often have reduced brain excitability. Drugs that affect the excitability of nerve cells can be effective in a variety of conditions in neurology and psychiatry. Novel ion channel blockers that reduce the excitability of pain nerves could contribute to a better treatment of chronic pain conditions.

In recent years, CHDR has gained experience in clinical studies with measurements of excitability in the brain, in muscle and in peripheral nerves. In all studies, researchers administer a series of stimuli and then measure and analyse the pattern of responses. Heuberger: 'Our approach to measure brain excitability is to stimulate the motor cortex with a transcranial magnetic impulse, using EMG to measure the response of the targeted muscle groups. Simultaneously, we register the EEG. This combination of measurements allows us to verify whether a candidate drug for epilepsy reduces excitability in healthy participants. If this is the case, this is a strong indication that the compound could be effective in patients. We are currently conducting a study with the same compounds in patients to see how well our results in healthy subjects translate to measurements in patients.'
Through excitability studies based on direct electrical stimulation of muscles, CHDR researchers showed that a selective ion channel blocker (ClC-1 blocker) had an effect in patients with the muscle disease myasthenia gravis. 'The measurement proved more sensitive and reproducible than conventional clinical measures, where subjective assessment by the investigator and motivation of the patient plays a major role,' Heuberger says. 'Thanks in part to our results, the manufacturer has now received follow-up funding to further develop the drug for this indication.'

According to Heuberger, excitability studies in individual nerves could be very valuable, even though this approach has yet to gain popularity in the field of drug development. 'In a peripheral nerve, one can achieve more precision than in cortical stimulation,' he says. Elsewhere in this annual report, we will show how his group uses this approach in pain research.

Heuberger is proud of what has been achieved since the Experimental Medicine group was founded. 'We have made a flying start, with two sponsored studies using these techniques this year. I hope we can contribute to the development of many more new drugs in years to come, and maybe even add more tools to our experimental medicine toolbox.'