Alzheimer’s disease is the most common form of dementia, and it may affect nearly 76 million people worldwide by 2030. The disease is progressive and eventually ends in death. No effective treatment is currently known. A type of protein called muscarinic acetylcholine receptor forms G protein–receptor complexes in the membranes of certain brain cells and plays a role in cognitive processing. In Alzheimer’s disease, the formation of amyloid proteins may decrease the ability of these receptors to transmit signals, contributing to Alzheimer’s disease progression. Agents called muscarinic agonists activate these receptors, so they may improve cognitive function in Alzheimer’s patients. These researchers are developing a new selective muscarinic agonist for the treatment of Alzheimer’s disease. It has the potential to promote brain cell survival and prevent the formation of amyloid proteins.
Scientific Synopsis
Muscarinic agonists might be useful in treating memory and cognitive deficits associated with Alzheimer’s disease. Moreover, muscarinic agonists may have a positive impact on the progression of Alzheimer’s disease through activating α-secretase, thereby preventing the formation of toxic β-amyloid (Aβ) peptides, and promoting neuronal survival. CDD-0102 is a small molecule that selectively activates M1 muscarinic receptors, exhibits a low side effect profile at doses that enhance memory function in rodents, and displays neuroprotective effects in cell culture. Ongoing efforts are focused on completing the preclinical studies necessary for filing an Investigational New Drug (IND) application with the FDA. Support is requested to complete the synthetic scale-up chemistry and manufacture sufficient quantities for completing a phase I clinical trial.
Lead Collaborator
University of Toledo, Ohio
William S. Messer, Ph.D.
Public Health Impact
Drugs that elevate acetylcholine levels (acetylcholinesterase inhibitors), such as donepezil and rivastigmine, produce modest improvements in memory function, but they elicit unwanted side effects and have little impact on disease progression.
Selective muscarinic agonists might be useful in the treatment of memory and cognitive deficits associated with Alzheimer’s disease with a lower side effect profile and might have an impact on disease progression.
Outcomes
Work on this project is complete. The investigator successfully filed an IND application using BrIDGs data and initiated clinical testing.
Project Details
- Synthesis of Good Manufacturing Practice (GMP) and non-GMP material
- Formulation development