Work on “Primary Sclerosing Cholangitis” (PSC)
Research goals (in order of decreasing importance):
- Finding an effective and convenient treatment that stops disease activity in myself
- Develop and offer a treatment to the public
- Advance the knowledge around PSC
Circumstances warrant that I will sacrifice scientific rigor and depth of my investigation for speed and clinical relevance in my research.
PSC is likely a multifactorial disease similar to other autoimmune diseases. My theory is that all PSC patients lack one or more essential microbial strains. The dysbiosis that follows leads to an abnormal bile metabolism, with one or more of the abnormal metabolites being responsible for the immune attack to the bile duct epithelium. This theory is advanced based on the 3 following observations:
- The microbiota is a complex microcosm and can be compared to our human society where a certain heterogeneity is required for a stable environment
- Fecal Transplant (adding bacteria from a healthy donor) temporarily improves the liver health status
- Vancomycin (eliminating some bacterial strains) temporarily improves the liver health status
Main research interests:
- I am looking at an array of bacterial metabolites with particular focus on metabolites of bacteria sensitive to the antibiotic vancomycin. These suspect metabolites inhibit the transformation of dopamine to epinephrine, so I am also looking at dopamine and epinephrine markers as well. I want to understand if there are metabolites that are elevated or decreased in PSC patients and if any of these metabolites correlate with disease activity and disease progression.
- In the same research context I am very interested in comparing before and after results of the analysis described in the first point as well as microbiome sequencing results in patients undergoing FMT or Vancomycin intervention.
- Backwards engineer why healthy fecal matter works when it works, isolate the strains responsible for the positive effect as much as possible starting from healthy fecal matter, with the ultimate goal of producing an effective therapy, more convenient than FMT.
Metabolites I am interested in (organic acids in urine):
- Clostridia bacteria markers: 4-hydroxyphenylacetic acid, 3-(3-hydroxyphenyl)-3-hydroxypropionic acid (HPHPA), 4-Cresol, 3-Indoleacetic acid
- Clostridia metabolites inactivate dopamine beta-hydroxylase (see Fig. below): Homovanillic acid (HVA), Vanillylmandelic acid (VMA) and HVA/VMA ratio
- (Intestinal inflammation, tryptophan metabolites (see Fig. below): 5-hydroxyindoleacetic acid (5-HIAA), Quinolinic acid (QIA) and QIA/5-HIAA ratio)
What does the research infrastructure look like:
I am currently working on this. I would like to involve my PSC Facebook Group with over >200 patients (as of Mar 2018) to source money and subjects for my research. I am considering carrying out my research based in Barcelona, ES, where I am looking for an optional research partner that can offer a laboratory.
I document my research journey publicly in the following youtube video playlist:
Thank you, Davide