As published in the Journal of Pharmacology and Experimental Therapeutics, BPN14770 was found to deter the effects of amyloid beta proteins in preclinical research. This drug was discovered in collaboration by Tetra Therapeutics and the University at Buffalo, and it is under development which is hope to lead to activate mechanisms that will support nerve health and prevent dementia. Additionally these benefits may also translate to Fragile X Syndrome, developmental disabilities, and schizophrenia.
Studies suggest that Alzheimer’s disease may develop in close to 25% of healthy 80 year olds without dementia which suggests that the body may turn to compensatory mechanisms to maintain the nervous system.
“Such observations imply that Alzheimer’s pathology can be tolerated by the brain to some extent due to compensatory mechanisms operating at the cellular and synaptic levels. Our new research suggests that BPN14770 may be capable of activating multiple biological mechanisms that protect the brain from memory deficits, neuronal damage and biochemical impairments.” said Ying Xu, MD, PhD, co-lead investigator and research associate professor in the UB School of Pharmacy and Pharmaceutical Sciences.
In animals studies BPN14770 was discovered to inhibit the activity of PDE4D enzymes which play roles in memory formation, learning, neuroinflammation, and traumatic brain injury. PDE4D lowers cAMP messenger molecules that signal physiological changes such as cell division, change, migration, and death leading to physical alterations in the brain; cAMP has several beneficial functions which include improving memory; by inhibiting PDE4D the drug increases cAMP signaling which protects against toxic effects of amyloid beta.
“The role of PDE4D in modulating brain pathways involved in memory formation and cognition, and the ability of our PDE4D inhibitor to selectively enhance this process, has been well studied,” said Gurney. “We are very excited by our colleagues’ findings, which now suggest a second protective mechanism of action for BPN14770 against the progressive neurological damage associated with Alzheimer’s disease.”
“Developing effective drugs for memory deficits associated with Alzheimer’s disease has been challenging,” said O’Donnell. “BPN14770 works by a novel mechanism to increase cyclic AMP signaling in the brain, which has been shown to improve memory. The collaborative project has led to clinical trials that will begin to test its effectiveness.”
Phase 1 studies involving healthy elderly people suggest BPN14770 is of benefit to working memory, and animal studies suggest it has the potential to promote maturation of connection between neurons which are impaired in patients with Fragile X Syndrome and helps to protects these connections which are lost with Alzheimer’s disease.
“There has been enormous interest in our ongoing Phase 2 trial of BPN14770 in 255 patients with early Alzheimer’s, and we are hopeful this study will show an impact of PDE4D modulation in this disease. Topline results are expected mid-2020,” said Gurney.
