Ongoing Projects
Investigating genetic factors involved in the development and onset of Post-Finasteride Syndrome
Tampere University in Finland will begin investigating possible genetic factors involved in developing Post-Finasteride Syndrome. This research will continue building upon 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 need to continue expanding into the why with more modern investigative techniques.
These efforts, combined with those already underway at The Institute for Human Genetics in Germany, hope to provide a more complete understanding of PFS, and why some patients experience persistent and severe health problems after discontinuing finasteride.
In this study, researchers will use a technique known as Whole Genome Sequencing (WGS) to analyse a cohort of PFS patients, looking for potential genetic factors that may predispose patients to developing the disease. The aims of investigating possible genetic factors involved in PFS are:
to understand the genetic predisposition to develop PFS
to understand why some individuals are affected and some are not
to prioritise genes implicated in the onset of the most common phenotypes
Understanding possible genetic factors involved in Post-Finasteride Syndrome could provide another path to accurate disease modelling in animals. Insights uncovered through research into patient genetics, along with potential insights from our existing line of scientific investigation, can contribute to establishing a disease model, with the objective of understanding the core pathomechanism and hopefully, an eventual target for precision medicine treatment of PFS.
An understanding of the predisposition will also:
clearly establish which consumers are at risk of developing PFS
help clinicians diagnose PFS faster and more accurately
Specifically, this study will use WGS to analyse the entire genome of 150 PFS patients compared to a group of healthy controls. WGS in principle allows the detection of disease relevant genomic variants beyond the exome such as DNA structural alterations, deep intronic variants, variants in non-coding regions, or repeat expansions and may improve variant calling in homologous sequences. It represents a novel, distinct diagnostic tool that targets genes and goes beyond the coding region and allows elucidation of established and novel non-coding genomic diseases.
The researchers involved in this project are accomplished in their fields and have a genuine interest in the disease. After extensive consultation and collaboration on our previous project, they are also aware of the multisystemic nature of PFS and other key peculiarities involved. The supervising lead, Dr Alfonso Urbanucci, has previously 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. Collaborative input will be provided by Professor Johanna Schleutker, an accomplished geneticist.
Elucidating epigenetic mechanisms as a cause of Post-Finasteride Syndrome
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, Dr Nadine Hornig, has diagnosed a molecular level androgen insensitivity driven by epigenetics as opposed to code variation. Another scientist lending his collaborative input, Dr Alfonso Urbanucci, 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.