Samantha Prins successfully defends her PhD thesis

On 05 April 2023, Samantha Prins successfully defended her PhD thesis titled ‘Healthy elderly in clinical trials - how to define preclinical Alzheimer’s disease for clinical trial participation’ at Leiden University.

With a growing elderly population worldwide, the occurrence of Alzheimer’s disease (AD) and thus the need for suitable treatment is also increasing. Currently only symptomatic treatment is available for AD patients. Despite the completion of more than a hundred phase 3 clinical trials, only one (possibly) disease modifying compound has been approved by the FDA. Potential reasons for this include the fact that many different pathophysiological changes play a role in the development of AD, and targeting just one of those may not influence the development or progression of AD sufficiently to slow disease progression, or the fact that not all patients with AD have the same alterations in AD related biomarkers. In addition, the timing of the initiation of treatment in patients with AD is also of great importance. Starting treatment in AD patients with irreversible neurological damage may lead to a negative clinical trial even though the compound demonstrated positive results in an earlier phase of the disease at which less structural damage is observed. The correct selection of trial participants is therefore of great importance. Pathophysiological changes such as Aβ formation and tau aggregation are already present and measurable up to 20 years before clinical disease onset and early intervention might prevent or delay a subject to become clinical. Drug development in AD is shifting its attention from performing trials in patients with clinically overt AD to subjects in the preclinical phase, prior to widespread brain damage and clinical symptoms of the disease have occurred, in the hope that this will lead to positive results.

In her thesis, Samantha describes several studies in healthy elderly subjects, subjects with preclinical AD and subjects with neurodegenerative diseases that were all aimed at gaining a better understanding of the difference between these subject groups and a better characterization of potential candidates for clinical trial participation in (preclinical) AD. In these studies, different biomarkers were investigated to gain more insight into healthy elderly, elderly with preclinical AD and patients with AD, in order to better understand the course over time of AD biomarkers as the disease progresses and to better select the optimal potential clinical trial participants for new disease modifying treatments being developed for AD. You can read Samantha’s thesis here.

Samantha was supervised by promotors Prof. dr. G.J. Groeneveld and Prof. dr. J.M.A. van Gerven and co-promotor dr. Laura Borghans.