Next generation xCDNF - In development for early Parkinson's disease
xCDNF is an engineered derivative of the CDNF protein targeted at treating neurodegenerative diseases with systemic administration
The drug candidate CDNF, which has advanced to clinical development, is a protein that does not pass the blood-brain barrier (BBB) effectively. The BBB is a semipermeable selective border of endothelial cells that separates the brain from circulating blood.
It was recently discovered that a certain smaller fragment of the CDNF protein maintains the neuroprotective and proteostasis-modulating activity and can also pass the BBB. Based on this discovery, Herantis has launched the development of xCDNF. Current available data suggests that the biological activity of xCDNF is comparable to full-length CDNF protein and can be administered, for example, by a subcutaneous injection (similar to, e.g., insulin injections), to reach the brain tissue. Herantis has developed and optimized a panel of novel xCDNF molecules with high potency, improved metabolic stability and brain distribution properties.
While xCDNF is a novel drug candidate and will require a complete preclinical development program, its development will significantly benefit from the methods and knowledge cumulated in the development of CDNF. This suggests that the early-stage development of xCDNF may be markedly faster than it was for CDNF.
Based on the same proteostasis-modulating mechanism of action, xCDNF will be primarily developed for early Parkinson’s disease. Other synucleinopathies, like Lewy body dementia, and possibly other chronic neurodegenerative diseases will also be of interest for future development.
Herantis’ goal is to start preclinical development with xCDNF in 2021. If successful, xCDNF would have potential to become a multi-billion-euro disease-modifying CNS drug.