£1.6 million grant awarded to advance development of MND drug candidate

Researchers from the University of Sheffield's Institute for Translational Neuroscience (SITraN) have been awarded a £1.6 million grant from the Medical Research Council (MRC). The grant will support their partnership with Aclipse Therapeutics to advance the translational development of M102 - a drug candidate for the treatment of motor neuron disease (MND).

Neuroprotective properties of M102 were discovered by SITraN researchers in 2013. Preclinical models evidenced the potential for M102 to slow down MND progression, which affects a patient's ability to walk, talk, eat and breathe.

The drug candidate activates the NRF2 (nuclear factor erythroid 2-related factor 2) and HSF1 (Heat shock factor 1) signalling pathways, which can work in combination to protect motor neurons from injury.

M102 has the potential to significantly slow down the disease progression in both familial and sporadic MND patients. The MRC grant will allow us to develop patient stratification biomarkers that will be applied in the M102 clinical studies, potentially enabling a personalised medicine approach in MND. This means that we can identify those who do and do not respond to M102 so we can target the treatment at those MND patients who are most likely to benefit. In addition, we will conduct, in collaboration with Aclipse, all the necessary development needed to reach the clinic. "

Dr Richard Mead, Principal Investigator on the Project

Co-applicant on the project Dr Laura Ferraiuolo said: "This project will use a methodology developed by my lab team to allow us to identify gene signatures that can discriminate between responders and non-responders to selected drugs. Our future aim is to be able to identify the best drug for each patient, making a huge step forward in drug efficacy and patient wellbeing."

Co-applicant on the project Professor Dame Pamela Shaw, Director of SITraN and the NIHR Sheffield Biomedical Research Centre said: "This funding award from the MRC is wonderful news for MND patients who are in desperate need of an effective therapy to address this life-threatening neurodegenerative disease."

"Along with my SITraN colleagues, Dr Richard Mead and Dr Laura Ferraiuolo, we led the MND biology research that enabled the development of M102, including the discovery of a potential precision medicine approach for M102 in MND, so we are very appreciative that MRC's funding support will allow us to take this exciting therapeutic approach to human clinical trials."

"We greatly appreciate the support from the MRC for our vision for a novel and broad multi-disease pathomechanism approach to treating MND patients," said Raymond K. Houck, CEO of Aclipse Therapeutics.

He continued: "The MRC award, coupled with our recent FightMND grant award, accelerates M102's development into its first-in-human clinical studies and validates M102's biology and potential for a precision medicine approach for the treatment of MND.

"The research funding from these programs will be key as they will support the completion of our investigational new drug (IND)-enabling work and the regulatory filings for first-in-human studies. Importantly, M102 may have applications in a wide array of conditions associated with impaired neuronal function such as Friedreich's ataxia, Huntington's disease and Parkinson's disease."

MND - also known as Amyotrophic Lateral Sclerosis (ALS) - affects approximately 5,000 people in the UK and 25,000 people in the US; with numbers expected to rise. MND is a disorder that affects the nerves - or motor neurons - in the brain and spinal cord that form the connection between the nervous system and muscles to enable movement of the body. The messages from these nerves gradually stop reaching the muscles, leading them to weaken, stiffen and eventually waste.

Currently, there is no cure for MND and no effective treatments to halt or reverse the progression of this devastating disease.