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A new drug discovered through a research collaboration between the University of Buffalo and Tetra Therapeutics could protect against memory loss, nerve damage and other symptoms of Alzheimer's disease.
Preclinical research has shown that the drug – called BPN14770 – deters the effects of beta-amyloid, a protein characteristic of Alzheimer's disease, which is toxic to nerve cells.
Recent studies show that Alzheimer's disease can develop without dementia in up to 25% of healthy 80-year-old patients, suggesting that the body could resort to compensatory mechanisms to maintain the nervous system.
BPN14770, being developed by Tetra Therapeutics, could help activate these mechanisms that promote nerve health and prevent dementia, even with progression of Alzheimer's disease.
According to the researchers, its benefits could also translate into fragile X syndrome, developmental disorders and schizophrenia.
"Such observations imply that the brain tolerates to some extent the pathology of Alzheimer's due to compensatory mechanisms operating at the cellular and synaptic levels," said Ying Xu, MD, PhD, principal investigator and associate professor of research at UB School of Pharmacy and Pharmaceutical Sciences.
"Our new research suggests that BPN14770 may be able to activate multiple biological mechanisms that protect the brain against memory deficits, neuronal damage, and biochemical alterations."
The study, published on September 5 in the journal Journal of Pharmacology and Experimental Therapeutics, was also led by James M. O Donnell, PhD, Dean and Professor at the UB School of Pharmacy and Pharmaceutical Sciences. Mark E. Gurney, PhD, President and CEO of Tetra Therapeutics, based in Grand Rapids, Michigan, collaborated on the research.
Keeping memory against toxic proteins
Research, conducted on mice, revealed that BPN14770 inhibits the activity of phosphodiesterase-4D (PDE4D), an enzyme that plays a key role in memory formation, learning, neuroinflammation and traumatic brain injuries.
PDE4D reduces adenosine cyclic monophosphate (cAMP) – a messenger molecule that signals physiological changes such as cell division, change, migration, and death – in the body, resulting in physical alterations in the brain.
cAMP has many beneficial features, including improved memory. By inhibiting PDE4D, BPN14770 increases cAMP signaling in the brain, ultimately protecting against the toxic effects of beta-amyloid.
"The role of PDE4D in modulating the brain pathways involved in memory formation and cognition, as well as the ability of our PDE4D inhibitor to selectively improve this process, has been the subject of many studies," he said. Gurney said. "We are very excited about the findings of our colleagues, who now suggest a second mechanism of BPN14770's protective action against the progressive neurological damage associated with Alzheimer's disease."
"The development of effective drugs for memory deficits associated with Alzheimer's disease has been a challenge," said O Donnell. "The BPN14770 uses a new mechanism to increase cyclic AMP signaling in the brain, which has improved memory.The collaborative project has led to clinical trials that will begin to test its efficiency."
Tetra Therapeutics is currently conducting Phase 2 clinical trials on BPN14770 in patients with early Alzheimer's disease and adults with Fragile X syndrome, a genetic disorder-causing disorder. intellectuals and development.
The results of previous phase 1 studies in healthy elderly volunteers suggest that the benefits of the drug are working or immediate memory. Animal studies have shown that BPN14770 could potentially promote maturation of connections between neurons, altered in patients with fragile X syndrome, and protect those connections, lost in patients with Alzheimer's disease.
"Our current phase 2 study on BPN14770 in 255 patients with early-onset Alzheimer's disease is of great interest, and we hope this study will show the impact of modulation. of PDE4D on this disease.The results of Topline are expected by mid-2020, "said Gurney.
The research was funded by the National Institutes of Health's Blueprint neurotherapeutic network, through the National Institute of Neurological Disorders and Stroke, the National Institute of Aging and the National Institute of Aging. mental health.
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