Moderator of 2 Sessions
Presenter of 2 Presentations
IMMUNO AND CHOLINERGIC THERAPY: ARE THEY COMPLEMENTARY IN AD TREATMENT?
Abstract
Aims
The recent registration in the USA of three new selective anti-a-beta antibodies (aducanumab, lecanumab, and donanemab) raises the question whether their use could be associated to the well established cholinergic therapy of AD, such as cholinesterase (ChE) inhibition.
Methods
The two therapeutic approaches differ substantially from one another both in aims and in targets. However, since the clinical outcomes used in clinical trials have been similar with both approaches (CDR-SB, MMSE, ADAS-cog and ADCS-ADL ) they can be directly compared
Results
Inhibition of ChE aims to compensate for the progressive reduction of synaptic acetylcholine (ACh), due to the unrelenting disease progression, by enhancing cholinergic neurotransmission. Thus, the target is ACh itself. The aim of immunization with monoclonal antibodies against a-beta is to reduce the presence of a-beta in the brain which is presumed to be correlated to disease progression. The target is the a-beta molecule itself. Although targets and mechanisms of action are quite different, the final goal is similar i.e., a significant and long-lasting improvement of the patients’ clinical conditions. A difference between the two approaches is the stage of the disease. Immunotherapy has been applied to MCI individuals while ChE inhibition to mild -moderate or severe AD patients. Another important difference is their effect on brain volume shrinkage and side effects.
Conclusions
Given both differences and similarities of the e therapeutical approaches, an interesting question and consideration is if the combination of monoclonal immunization with ChEI treatment, would complement each other in effect and therefore represent a therapeutical advantage.