Elucidating epigenetic mechanisms as a cause of Post-Finasteride Syndrome

Announced in November 2021, this study has been fully funded as of January 2022. Sample collection has begun as of February 2023. We anticipate sample collection, culturing, and basic AR expression analysis to take up most of 2023.

The Institute for Human Genetics at the University Medical Center Schleswig-Holstein will be building on the important results from Baylor College of Medicine. These landmark findings demonstrated significant deregulation of gene expression in PFS patient tissue which correlated to observed biological differences in patients and their self-reported symptoms. While Baylor’s results indicate a what, we now need to expand into the why with more modern investigative techniques.

The objective of this research is to investigate induced epigenetic changes, including altered methylation in the AR regulatory region, or alterations to the chromatin landscape, which may underlie a pathologically changed sensitivity to androgens and the widespread dysregulation of gene expression discovered in Baylor’s research. Elucidation and understanding of disease mechanisms is a necessary step in identifying potential treatments of Post-Finasteride Syndrome.

In this study, researchers will use state-of-the-art high throughput sequencing to investigate potential changes in the spatial organisation of chromatin. Chromatin structure is a key component in gene expression, and identifying changes could provide key insights into the pathological drivers underlying altered gene expression in Post-Finasteride Syndrome.

This investigation is crucial as identification of driving epigenetic changes will allow for accurate modelling of Post-Finasteride Syndrome in animals. Such modelling will help us understand the core pathomechanism and hopefully identify targets for therapeutic treatments of PFS to benefit you or your loved one.

The scientists involved in conducting this research have world leading expertise. The supervising lead has diagnosed a molecular level androgen insensitivity driven by epigenetics as opposed to code variation. Another scientist lending his collaborative input has published in Cell reports evidence that overexpression of the AR is able to drive genome-wide chromatin relaxation and gene expression alteration in refractory prostate cancer. Finally, sequencing and interpretation expertise will be lent by a professor who reviewed the state of the art in structural and quantitative chromosomal rearrangements, their analysis, and role in disease in Nature reviews.