Today we announce a new collaboration for a preclinical research study on the diabetes drug liraglutide, in the hope that positive results will lead to a clinical trial in MND. Here’s a little more about the rationale behind the study.
The idea that drugs licensed for one disease may have some use in another completely different disease is not new, but it has gained much more attention in recent years. Researchers are developing a new understanding of disease processes, leading to new ‘drug repurposing’ opportunities, with the additional potential to reduce the time and cost of drug development.
Significant advances in genetics and molecular biology in recent years have greatly increased our understanding of the pivotal, carefully balanced cellular processes that usually keep motor neurons healthy but, when disrupted, can cause a cascade of degeneration leading ultimately to their death.
The idea of exploring the potential usefulness of certain types of anti-diabetic drug goes back to research showing that diabetes is a risk factor for Alzheimer’s disease and Parkinson’s disease. The link between diabetes and MND is much less clear, but we do know that one of the long term secondary consequences of diabetes is damage to sensory and sometimes motor nerves, so at the very least we can say that diabetes is unlikely to help MND!
In treating diabetes, liraglutide and related drugs control the release of insulin by binding to a specific protein binding sites on the cell surface of the pancreas, called ‘GLP-1 receptors’. However, these receptors are also found in cells in the brain where they appear to play a role in maintaining the metabolic health of neurons. The implications for treating neurodegenerative diseases stems from research showing that activation of these receptor sites with drugs can protect neurons from damage.
Based at the University of Lancaster, Prof Christian Hölscher is one of the leading experts on the protective effects of GLP-1 receptor activation. His extensive lab-based studies in models of Alzheimer’s disease and Parkinson’s disease have been instrumental in forming the basis for emerging clinical trials in both conditions.
The level of evidence for a similar role in MND, however, is currently limited to a study of a related drug, exendin-4, which showed cellular protection in cells in culture and also improved some disease symptoms (but not overall survival) in the SOD1 mouse model of MND. Exendin-4 is not particularly good at getting from the bloodstream into the brain, which is why attention has moved to the more recently developed drug, liraglutide, known to access the central nervous system more easily and at lower doses, which would also reduce the likelihood of potential side effects.
Prof Hölscher will collaborate with Dr Richard Mead and his team at the Sheffield Institute for Translational Neuroscience, where the research studies will be carried out. It will take many months before the preclinical MND studies are completed, but in the meantime, clinical colleagues will seek to firm up plans for a clinical trial, in anticipation of promising results from the lab.
For more info on how we approach funding MND research involving animals, go to www.mndassociation.org/animalresearch.