Increasing endogenous degradation of amyloid beta as a treatment strategy for Alzheimer’s disease

Alzheimer’s disease (AD) is caused by increased levels of amyloid beta (aβ) in the brain, leading to the formation of toxic aggregates.

Endogenous aβ is degraded by neprilysin, and in AD patients, neprilysin levels are lower and thus a likely cause of AD.

Somatostatin (SST), which is also reduced in AD patients, promotes the production of neprilysin, both intracellularly and extracellularly. The overall aim of this study is to develop a therapeutic strategy that will prevent all aβ aggregates to form. More specifically this will be done by delivering SST to the brain, either by protein therapy or gene therapy.

Protein therapy: We have developed an efficient blood brain barrier (BBB) transporter that enables brain delivery of proteins which normally wouldn’t be able to cross the BBB (like SST).

Here, we will investigate if SST linked to our BBB transporter can reduce aβ levels and pathology in mice models of AD.

Gene therapy: Recently, strains of adeno- associated viruses (AAV) that efficiently can pass the BBB have been developed.

We have generated such an AAV with a SST gene, and we will evaluate if this can reduce aβ levels and pathology in mice models of AD. Cognitive studies.

With the most promising strategy from 1 or 2 we will do behavioral studies to study the effect the treatment has on cognition.Current AD treatments only alleviate symptoms. However, enhancing the degradation of aβ have the potential to stop the cognitive decline in AD.