New Metal-Protein Attenuating Compounds with Neurotrophic Properties as a Therapeutic Strategy in Alzheimer's Disease

Alzheimer?s disease (AD) is the most common form of dementia, a devastating disease characterised by the loss of mental function. Large numbers of patients are affected by this disease worldwide, and as the world population is aging, the impact of this disease is ever increasing. None of the drugs used to treat patients at present affect significantly the disease. There is evidence that in the brain of patients with Alzheimer?s disease there is an imbalance in the activity of metals such as zinc and copper. There is a high concentration of these metals in areas of the brain affected by the disease, and it is believed that this process is responsible for brain damage. There is evidence that drugs that can bind these metals and reduce their concentration could affect beneficially the patients, and change the disease course. We know already that this new type of drug is likely to be well-tolerated, and there are already some observations which support the idea that these drugs can improve significantly the mental deterioration in patients. Our project is to develop new and improved drugs which can bind excess metals and thus reduce the toxic processes in the brain of patients with dementia. The funding will help us choose the best compound which could be tested in the next few years in patients.

Alzheimer‘s disease (AD) is the most common form of dementia, a devastating disease characterised by the loss of mental function. None of the drugs currently on the market affect significantly the disease. Anti-amyloid strategies are at the core of AD research, and it has been shown that Metal Protein-Attenuating Compounds (MPACs) which bind zinc and copper, reduce amyloid load and toxicity. Clinical trial results with MPACs which are quinoline compounds show excellent tolerability and improved cognition in AD patients and therefore show that MPACs are promising new AD drugs. Our project aims to further develop new substituted phosphonate MPACs, and facilitate the selection of a compound for Phase 1. Our proprietary non-quinoline MPAC compounds have additional and unique neurotrophic properties, which are particularly relevant in the context of AD, making these compounds better than the existing MPACs. The project will provide in vitro and in vivo efficacy data, safety, toxicity, metabolism and pharmacokinetic data, and thus facilitate the choice of a candidate compound for first studies in man.