SFRP1 as a Therapeutic Target and Diagnostic/Prognostic Factor in Alzheimer’s Disease

2020, 2022

2022

Patients with Alzheimer’s disease (AD) present with a disease-dependent increase in the brain expression of a small glial-derived secreted protein named SFRP1, which interacts with harmful amyloid products (among the culprit of the pathology) and downregulates an enzyme that prevents their generation. Neutralization of SFRP1 activity in mice counteracts several of the pathological traits of the disease when administered at early stages of the disease. We have now begun to explore further the potential of immunoglobulin-based SFRP1 neutralization as a therapeutic strategy for AD. Our studies so far indicate that the treatment does not produce evident side effects even after three months of treatment. It also shows effectiveness when the animals with a consolidated pathology are treated. In contrast to this encouraging data, we have determined that plasma levels of SFRP1 cannot be used as a reliable diagnostic factor for AD, as we had initially postulated.

2020

There is increasing evidence that Alzheimer’s disease not only involves neurons, but also other cell types present in the brain, such as glial cells. Understanding glial cells’ contribution to the pathology therefore promises conceptual advances and, at the same time, offers an important window of opportunity for identifying new therapeutic targets. We recently have shown that patients with Alzheimer’s disease present a disease-dependent increase in the brain expression of a small glial-derived secreted protein named SFRP1, which interacts with harmful amyloid products (the accumulation of which is thought to be among the culprits of the pathology), and down-regulates an enzyme that prevents their generation. Studies in mouse models showed that neutralization of SFRP1 activity counteracts several of the pathological traits of the disease. We now wish to obtain preclinical evidence that this strategy is effective against Alzheimer’s disease progression—and safe, so that treatment will have no relevant side effects. We also will explore whether the presence of SFRP1 in the serum may be predictive of disease progression. We expect this study will provide the necessary information to translate a novel therapeutic target and possibly an additional diagnostic tool for AD to the clinic.


Funding to Date

$345,000

Focus

Biomarkers/Diagnostics/Studies of Risk & Resilience, Foundational

Researchers

Paola Bovolenta, Ph.D.


Pilar Esteve, Ph.D.