Breakthrough in Diabetic Neuropathy Research: Blocking CDK5 Hyperactivity Restores Nerve Regeneration
Diabetes frequently leads to debilitating nerve damage, causing pain, numbness, and limited mobility in millions worldwide. A key challenge in treating this condition has been understanding why damaged nerves fail to adequately regenerate. Now,researchers at the University of Cologne have pinpointed a critical mechanism behind this failure and demonstrated a promising therapeutic approach to restore nerve growth.
Led by Professor Dr. Dietmar Fischer of the Institute for Pharmacology II and the Centre for Pharmacology at the University Hospital of Cologne, the team’s findings, published in Science Translational Medicine, reveal that the protein p35 accumulates in nerve cells in both type 1 and type 2 diabetes models. This accumulation triggers hyperactivity of the enzyme CDK5, initiating a signaling cascade that effectively halts nerve fiber regrowth.
The researchers successfully bypassed this blockage through targeted interventions. Using both genetic manipulation and newly developed peptides – small protein building blocks administered systemically – they where able to reduce p35-mediated CDK5 activity. This resulted in nerve fiber regeneration rates comparable to those observed in healthy animals, accompanied by significant improvements in both motor and sensory function in preclinical models.
“Our results demonstrate, for the first time, that nerve regeneration in diabetes can be restored to levels similar to those seen in healthy individuals by preventing the excessive activation of this signaling pathway,” explains Professor Fischer. Importantly, the treatment proved effective even after diabetic neuropathy had already developed. The team has patented a especially promising peptide that directly addresses the root cause of the problem and holds potential for future drug development.
Interestingly, the study also found that this impaired regenerative capacity occurs before the onset of clinical diabetic neuropathy, suggesting a potential window for preventative intervention. Professor Fischer’s team is currently investigating whether targeting this mechanism can prevent the development of neuropathy itself.
This research offers a significant step forward in the treatment and potential prevention of nerve damage associated wiht diabetes, a widespread and currently incurable condition. the discovery of p35/CDK5 hyperactivity as a key driver of nerve regeneration failure provides a novel therapeutic target and opens new avenues for improving the lives of millions affected by diabetic neuropathy.
Original publication: Philipp Gobrecht et al.; Failure of nerve regeneration in mouse models of diabetes is caused by p35-mediated CDK5 hyperactivity; Science Translational Medicine November 2025, DOI: 0.1126/scitranslmed.adp5849.
