Development of cutting-edge combination therapy using neurotrophin, anti-amyloid and galantamine therapy for Alzheimer´s disease

Alzheimmer´s disease (AD) is a complex and deadly disease.

Recent clinical trials reported beneficial effects of anti-amyloid immunotherapies on  cognitive decline, but the cognitive effects are small and clinical relevance debatable. The anti- amyloid antibody lecanemab significantly clears amyloid from the brain.

We have previously shown positive effects with drugs targeting the cholinergic system (ChEIs) and the neurotrophins (NGF).

Could a combination therapy aiming at these three targets improve behavior/memory and change biomarkers?I propose here that one solution to treat the complexity of Alzheimer ́s disease (AD) is to target several mechanisms through combination therapy using 1. Neurotrophic molecules like NGF which holds promise for effective revival of neurotrophic pathways. 2.

A base treatment with the cholinesteraseinhibitor galantamine targeting the cholinergic pathways and shown to decrease risk for severe dementia and improve survival. 3. Treatment with the anti-amyloid antibody lecanemab. To show proof of concept, the combination will be tested in an AD mouse model.

In preparation for a human trial, biomarkers in human samples will also be analyzed and epidemiology in a large population of AD patients performed to understand AD progression long-term.

If successful it can open up for a clinical trial in AD patients and thus hope for the development of a multi-mechanistic approach for AD with a potential to help millions of individuals.