Statins may be efficient treatment for clients with ulcerative colitis.
There might be good news for the nearly 1 million people fighting ulcerative colitis, a kind of inflammatory bowel condition with no real treatment: Statins, a typically prescribed cholesterol-lowering drug, appear to be an effective, if unforeseen, treatment for the condition, according to a brand-new Stanford Medicine study.
Presently, the only lines of defense versus ulcerative colitis are anti-inflammatory drugs, which do not constantly work, and a colectomy, the surgical elimination of part or all of the colon. Finding another alternative is significant, stated Purvesh Khatri, PhD, associate teacher of medicine and of biomedical data science, who led the research.
” About 30% of ulcerative colitis patients ultimately have to undergo a colectomy as a last resort. Its an extreme measure; youre removing part of your body,” stated Khatri. “So we believed, Can we use readily available information to see whether drugs that are already approved by the FDA can be repurposed to better treat these patients?”.
From there, it was matter of determining how particular drugs impacted the gene activity associated with ulcerative colitis. The concept was to find the drugs that seemed to reverse the gene signature associated with ulcerative colitis. If clients with ulcerative colitis had a dip in the activity of gene A and B, the group looked for drugs that increased activity in those genes. After cross-referencing the speculative and genomic sets of information, the group determined three drugs that effectively reversed the gene signature of ulcerative colitis. Statins are among the most commonly prescribed drugs in the United States, so it appeared reasonable to believe that a reasonably big number of clients with ulcerative colitis might also be taking statins to assist handle their cholesterol.
Ulcerative colitis triggers swelling and ulcers in the bowel, leaving patients susceptible to a range of unpleasant signs, consisting of stomach discomfort, blood in the stool, irregularity and fatigue. The condition, while not life threatening, can be severely debilitating, particularly if anti-inflammatory medications do not work.
By using openly offered datasets of anonymized client health information, consisting of genomic and prescription information, Khatri and his team found a connection in between a handful of drugs and decreased symptoms of ulcerative colitis. As it turned out, atorvastatin, sold under the brand name Lipitor, was one of the top performers, substantially decreasing the rate of surgical treatment for ulcerative colitis, the need for anti-inflammatory medication, and hospitalization rates.
A paper explaining the research study was published on September 16, 2021, in the Journal of the American Medical Informatics Association. Khatri is the senior author. Graduate trainees Lawrence Bai and Madeline Scott are co-lead authors.
Evaluating genes and drugs effects on them.
Khatri and his team started their research study by analyzing openly readily available genomic information from hundreds of clients with ulcerative colitis who had actually gone through a colon biopsy, a somewhat typical practice that helps physicians diagnose the disease and its severity. Particularly, Khatri and his team were searching for specific genomic “signatures,” or patterns of gene activity, that appeared to continue many patients with the condition.
” We looked at nationwide and worldwide data, and we found a disease signature that was robust throughout all the datasets regardless of whether the client was experiencing a flare in illness,” Khatri said.
From there, it was matter of identifying how certain drugs impacted the gene activity associated with ulcerative colitis. If clients with ulcerative colitis had a dip in the activity of gene A and B, the team looked for drugs that increased activity in those genes.
Statins emerge.
After cross-referencing the genomic and experimental sets of data, the group identified 3 drugs that effectively reversed the gene signature of ulcerative colitis. “The very first two were chemotherapy drugs, which naturally you wouldnt recommend to somebody due to major adverse effects, however the third was a statin. Statins are generally safe enough that some doctors joke they ought to be put in the water,” Khatri said.
The next action would normally be to set up a scientific trial. Ever the data enthusiast, Khatri took a different approach. Statins are among the most commonly recommended drugs in the United States, so it seemed reasonable to think that a relatively big number of patients with ulcerative colitis might likewise be taking statins to help manage their cholesterol. Rather of turning to a clinical trial, the group turned to information from electronic health records. “We were able to see if they had ulcerative colitis, if they were on statins and whether they d needed a colectomy,” Khatri said.
People with ulcerative colitis who were taking statins, no matter their age, had about a 50% decrease in colectomy rates and were less likely to be hospitalized. In addition, ulcerative colitis clients who were taking statins were prescribed other anti-inflammatory medications at a lower rate.
While its not totally understood how statins quell symptoms of the disease, Khatri said they are known to have some sort of general anti-inflammatory capability.
” At this point, one could argue that this information reveals a strong adequate connection to begin recommending statins for ulcerative colitis,” Khatri said. “I think were practically there. We require to verify the results a bit more stringently before moving it into the clinic.”.
The other advantage of the research study, Khatri stated, is that it supplies a framework for how to suss out drugs that are already in circulation and repurpose them to deal with other illness. The system, he said, is rife with potential, particularly for autoimmune diseases.
Reference: “Computational drug repositioning of atorvastatin for ulcerative colitis” by Lawrence Bai, Madeleine K D Scott, Ethan Steinberg, Laurynas Kalesinskas, Aida Habtezion, Nigam H Shah and Purvesh Khatri, 16 September 2021, Journal of the American Medical Informatics Association.DOI: 10.1093/ jamia/ocab165.
Other Stanford co-authors are graduate students Ethan Steinberg and Laurynas Kalesinskas; teacher of medicine Aida Habtezion, MD; and teacher of medicine and of biomedical information science Nigam Shah, MD, PhD.
The research was supported by the National Institutes of Health (grants 1U19AI109662, U19AI057229 and 5R01AI125197), the Stanford University Medical Scientist Training Program, the Bill and Melinda Gates Foundation, the Department of Defense, and the Ralph & & Marian Falk Medical Research Trust.