Alzheimer’s disease (AD) is a complex and poorly understood disorder that ultimately leads to neurodegeneration in patients afflicted with the disease. The pathophysiology of AD is still unknown; however, some scientists believe that viruses play a role in the development of AD, as demonstrated in a recent study.
In a study published in the June 21 issue of the journal Neuron, researchers analyzed data from postmortem brain tissue samples of people with and without AD, finding increased levels of the two Roseoloviruses, human herpesvirus 6A (HHV-6A) and human herpesvirus 7 (HHV7), demonstrating the theory that viruses may have a role in AD biology. However, researchers believe that the viral mechanisms could generate the disease but not be a main cause in AD progression.
Originally, scientists from Icahn School of Medicine at Mount Sinai, New York City, and Arizona State University, Phoenix, were looking to find evidence that drugs used to treat other diseases can be reused for the treatment of AD patients. They conducted RNA sequencing on data from three brain banks to evaluate differential viral profusion in AD and compare biological networks undiscovered in AD. Researchers, using computational tools to analyze large datasets, found that there are multiple points of overlap between virus-host interactions and genes associated with AD risk; human herpesvirus 6A and 7 were found in AD samples at levels up to twice as high as AD disease samples and the biology of AD across domains (RNA, DNA, and proteins) is influenced by multiple viruses. Furthermore, they confirmed the link between neuropathological traits of AD such as amyloid plaque density and clinical dementia rating score and viral load.
According to GlobalData’s analysis of the AD pipeline, amyloid precursor protein (amyloid beta peptide and protein) and microtubule associated protein tau (MAPT) are the major targets in focus for the development of vaccine. Out of 31 vaccines in development, 14 target amyloid precursor protein and 10 vaccines target MAPT. Capo Therapeutics is leading the development of the vaccine pipeline with seven candidates in the preclinical stage.
Currently, in the late-stage pipeline for AD, there is an interesting vaccine, CAD106, developed by Novartis. CAD106 is an active vaccination strategy that aims to elicit a strong Aβ-specific antibody response while avoiding T cell auto-immune responses. Development of vaccines against beta amyloid was undertaken for the first time in this field, with no success, by Elan Corporation with its product, AN1792, as the drug triggered meningoencephalitis. However, there were no signs of that in the CAD106 trial and positive results of safety and efficacy from Phase II study were presented at the 13th International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD) in 2017 with the title “BACE inhibitor CNP520 proposed for the Alzheimer’s prevention initiative generation study.” In November 2015, Novartis began a Phase II/III trial in partnership with the Banner Alzheimer Research Institute, which is set to run until 2023 with a five-year treatment period. This vaccine could have potential to slow the development of the disease and fill unmet medical need in AD.
The AD pipeline has been characterized by big failures, as AD drug development is considered to have the highest failure rates of all indications, more than cancer drugs. More research is needed to test these vaccine benefits in AD patients, but this new evidence can open new development opportunities for drugmakers, bringing new treatments for AD, and could be a step forward in AD research.