Diabetes significantly increases the risk of dementia, by at least two- fold. However, we still do not fully understand the link between the two, and lack effective medicines to treat either condition.
Diabetes mellitus (DM) is a complex metabolic illness, affecting at least 10% of the adult population in the Maltese islands, placing Malta in the first quartile within the European region. The potential health complications of DM are multiple and devastating, and few organs are spared: heart disease, stroke, kidney failure, limb amputations, loss of sight, poor healing and increased risk of infection, and even an early death. Not least, people with DM are 2-to-5 times more prone to developing Alzheimer’s dementia (AD) – thus directly linking these two modern-age epidemics. This scenario poses a significant healthcare challenge to the National Health Service, and a colossal economic burden for the country as the number of affected people rises inexorably: cases of type-2 DM in the under-40s have increased 39% in recent years. Despite the fact that DM is a healthcare emergency, however, we still do not have the right tools to fight it. Most importantly, current medications do nothing to slow down progression of the disease. In our laboratory at the Dept. of Physiology and Biochemistry of the University of Malta (UM), we are actively working on just that: developing the drug pipeline for new innovative medicines that will have a direct impact on disease.
As Professor in Physiology and Biochemistry, I lead a team of researchers dedicated to the study of those diseases associated with the abnormal clumping of rogue proteins (known as “amyloid”) in human tissues. Amyloid clumps can form practically anywhere in the body: thus, in diabetes mellitus we find amyloid deposits in the pancreas, destroying the insulin- producing cells; whilst in Alzheimer’s, amyloid plaques develop in the brain causing loss of memory. Key questions that we are currently addressing in our research include: how do these amyloid clumps form? Why are they so damaging to the brain and the pancreas? And most importantly: can we develop new medicines that can stop amyloid from clumping in the first place, or at least reduce its harmful effects?
We have started making significant in-roads in answering these questions. For instance, in our lab, we have discovered one key mechanism of amyloid toxicity which involves damage to mitochondria, the cell’s energy powerhouses. Mitochondrial dysfunction leads to a bioenergetic collapse: hence, insulin- producing pancreatic cells die and do not release insulin; while neurons in the brain responsible for our memories are silenced. We have published this important body of research in peer-reviewed scientific journals of respected academic publishers and societies, such as: Scientific Reports (Nature Publishing Group), ACS Chemical Neuroscience (American Chemical Society), EMBO Molecular Medicine (European Molecular Biology Organisation), the Proceedings of the National Academy of Sciences of the USA, and FEBS Letters (Federation of European Biochemical Societies), among others. According to the scientometric data analysis website exaly.com, research generated from my lab has an h-index (a metric that measures both the productivity and citation impact of the publications) in the top 10% worldwide.
As mentioned, we hope to develop new medicines for treatment of diabetes and dementia. In this regards, we have forged strong international collaborations with top German research institutions: the Ludwig-Maximilian-University and the Centre for Stroke and Neurodegenerative Diseases in Munich, and the Max Planck Institute for Multidisciplinary Sciences in Göttingen, Germany. In particular, my research team at UM has contributed to studies on the compound anle138b, patented by the German biotech company MODAG GmbH, and undergoing phase-II clinical trials. Current projects involve testing anle138b and related compounds in models of DM and dementia.
It should also be mentioned that research projects have provided upskill training for (to date) 10 M.Sc. students (4 of them on internships from German, Austrian and Czech universities) and 5 Maltese Ph.D. students. Such training broadens the skillset of the students and helps them develop their transferable skills, which will ultimately allow them to operate more effectively in different work environments.
To conclude, I am enthusiastic that, with continued investment and financial support, we will persist in making internationally-recognised contributions to accelerate the development of new medicines for DM and AD. Other ‘spillover benefits’ include addressing Malta’s Research and Innovation Smart Specialisation Strategy (2021-2027), enhancing the University of Malta’s international ranking, and impacting local R&I and employment opportunities by supplying Highly Qualified Personnel for advanced medical research and pharmaceutical sectors in Malta.
“With continued investment and financial support, we will persist in making internationally-recognised contributions to medicine and advance the R&D sector in Malta .”