Targeting the right suspect: DNA Vaccination strategies in Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative disorders and the most common cause of dementia. It is characterized by the aggregation of amyloid β protein (Aβ) into extracellular plaques in the brain and the accumulation of neurofibrillary tangles containing tau protein within neurons. These pathological changes lead to neuronal dysfunction, as well as inflammation and neurotoxicity, all of which result in cognitive impairment affecting memory and behavior. Various therapeutic strategies have been proposed and developed in recent years to specifically target Aβ peptides in order to eliminate amyloid plaques. However, it is important to choose the right immunization strategy, i.e. to generate the immunogen most representative of the target and its effective control by the immune system .

From immunization to monoclonal antibody immunotherapy, Aβ has been central to the development of therapeutic strategies for Alzheimer’s disease. The first promising results were obtained 20 years ago with a peptide-based vaccine that generated a response against Aβ1-42. However, the combination of the 1-42 peptide and the adjuvant used to trigger a sufficiently strong immune response also increased the frequency of meningoencephalitis, a form of brain inflammation, in patients. However, other peptide-based vaccination strategies developed to avoid the Th1-stimulating region of the Aβ1-42 peptide lacked clinical effectiveness. Currently, monoclonal antibody-based immunotherapies targeting the Aβ1-42 peptide have all resulted in inconclusive or mixed results ,.

New immunization strategies have also shown promising results. Among them, Lambracht-Washington et al. recently used a DNA immunization formulation encoding Aβ1-42 in the well-established 3xTg-AD transgenic mouse model. This active immunotherapy strategy was associated with an overall improvement in the various parameters assessed in their study (proinflammatory genes, Ab and Tau accumulation). This alternative immunization method had the advantage of avoiding Th1 stimulation while generating antibodies that efficiently recognized Aβ1-42 present in amyloid plaques (,,). Although other strategies for treating Alzheimer’s disease have yet to be developed, there is still hope for an effective anti-Aβ1-42 strategy, as long as we target the right “suspect” and generate the right immune response.

At MediMabs, we provide a thorough analysis of your target to find and propose the best strategies for your project. Whether you need to develop a vaccination strategy, a de novo monoclonal or polyclonal antibody, or need one of our commercially available antibodies, we will help you find the right service or product for your needs.

Written by
MédiMabs’ Team
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