Question

How would you go about developing a vaccine for Alzheimer’s disease?

What would you target?

What is the evidence for this target(s)?

How would the immune system attack this target?

What are the normal physiological functions of the target?

What are the potential complications or side effects of such a vaccine?

Answer 1

The vaccine is designed to provoke an antibody response against beta amyloid, clearing it away, without triggering potentially damaging inflammation. United Biomedical used its UBITh technology to identify the peptide for the vaccine. The company packaged it in a proprietary vaccine-delivery system.

Alzheimer's disease (AD) is the most common cause of age-related cognitive decline. Both active and passive immunization paradigms have illustrated the potential to prevent and reverse established AD pathology in transgenic and non-transgenic animal models of AD. Follow-up studies have shown that changes in amyloid burden observed with immunization could rescue cognitive deficits in both young and aged mice. Despite the success of immunotherapy in animal models, clinical trials were halted early. It has become clear that more preclinical work was needed before initiating trials, as most of the adverse events observed in patients could have been predicted using animal models. Despite these setbacks, clinical trials have demonstrated the utility of amyloid-beta (Abeta) vaccination in reducing amyloid pathology and potentially reducing cognitive decline.

Clinical trials using a safer vaccine, which is potent enough to elicit a robust antibody response in the absence of encephalitis may prove effective in mitigating progressive neurodegeneration seen in AD. If so, Abeta vaccination could supplant current symptomatic treatment and represent one of the first therapeutic options for AD based on the amyloid cascade hypothesis.

lthough the exact cause of AD is not yet known, there are common features observed among affected patients, the presence of Aβ plaques being one of them and arguably the most common target for immunotherapeutic approaches. Experiments carried out by Schenk and colleagues in 1999 were the first to demonstrate that immunization with the Aβ peptide could reduce the deposit of plaques in the brain of mice genetically modified to develop AD with symptoms similar to those observed in humans

Studies performed during the last century allowed the identification of distinct features of AD, such as the accumulation of Aβ plaques in the brain, and the relationship of these deposits with the clinical manifestations. These observations opened perspectives for new therapeutic interventions for the control of the disease, particularly during the last decade. Studies focused on vaccines have advanced significantly and now represent a promising therapeutic alternative for disease control, based on the generation of antibodies against the Aβ peptide. These advances were accompanied by retreats, as in the case of the first clinical trials, that provided important lessons for researchers, who have deepened their knowledge and developed alternatives for the design of safer and more effective vaccines for the control of AD. Recently, the possibility of targeting proteins other than Aβ has been tested, and promising results are expected to be seen with the Tau protein, but clinical data are still lacking, and should be pursued in this kind of approach.