Researchers have decoded the signaling pathway that inhibits nerve regeneration in diabetes and developed a therapeutic peptide that offers new perspectives for the treatment and possibly prevention of diabetic nerve damage.
Nerve damage is one of the most common and at the same time most stressful complications of diabetes. Millions of patients worldwide suffer from pain, numbness or restricted mobility – not least because damaged nerve fibers do not grow back sufficiently for reasons that are still unclear. A research team led by Professor Dr. Dietmar Fischer from the Institute for Pharmacology II of the Medical Faculty of the University of Cologne and Director of the Center for Pharmacology at the University Hospital of Cologne has now identified a central mechanism that explains this limited regeneration in diabetes. Building on this, the researchers succeeded in developing a promising therapeutic approach that can increase regeneration. The results were published in the journal Science Translational Medicine under the title “Failure of nerve regeneration in mouse models of diabetes is caused by p35-mediated CDK5 hyperactivity”.
In mouse models of type 1 and type 2 diabetes mellitus, the team demonstrated that the protein molecule p35 accumulates significantly in nerve cells. This protein activates an enzyme that sets off a signaling cascade that blocks the regrowth of nerve fibers. This significantly limits the natural ability of the nerves to regenerate. Through targeted interventions in this signaling pathway – either using genetic methods or, pharmacologically, with newly developed small protein building blocks (peptides) that can be administered systemically – the scientists were able to remove the blockage. In the preclinical models, the nerve fibers then grew again at a similar rate as in healthy animals. This was accompanied by significant motor and sensory improvements.
“Our results show for the first time that nerve healing in diabetes can be brought to a level comparable to that of healthy animals if excessive activation of the signaling pathway is prevented,” says Professor Fischer. “An improvement in regeneration occurs even when diabetic neuropathy is already manifest.” A particularly promising peptide developed and patented by his working group is that it addresses the cause directly and could in principle be suitable for further development as a medication.
It is also noteworthy that the regenerative weakness caused by diabetes occurs before the onset of diabetic neuropathy – a common complication that affects almost half of all patients. Professor Fischer and his team are currently conducting another study to determine whether the discovered mechanism also directly contributes to the development of this nerve disease or whether the risk can be reduced using new treatment options.
The current study opens up new perspectives for the treatment and possibly also for the prevention of nerve damage in diabetes or diabetic neuropathy, one of the most common and currently incurable secondary diseases worldwide.
Content contact:
Professor Dr. Dietmar Fischer
Center for Pharmacology
Institute of Pharmacology II
dietmar.fischer@uni-koeln.de
Press and communication:
Dr. Anna Euteneuer
+49 221 470 1700
a.euteneuer@verw.uni-koeln.de
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