Gout (gotta, in italian) is a form of arthritis caused by a buildup of uric acid crystals around the joints. The body produces uric acid as it breaks down purines, one of building block of nucleic acids. Uric acid levels in the blood rise (hyperuricemia) with gout, and hardened accumulations of the crystals (tophi) may also form under the skin around affected joints. Studies have linked gout with chronic inflammation and obesity, two conditions that contribute to metabolic syndrome. Metabolic syndrome is a group of factors that increase the risk of diabetes, heart disease and stroke. Gout is a dangerous and underdiagnosed condition. However, the definition of metabolic syndrome does not include gout, although it is a severe and common metabolic disorder potentially leading to chronic kidney disease (CKD). New research suggests that an individualized probiotic therapy regimen may improve symptoms of gout, gout-related kidney disease and other signs of metabolic syndrome. The study is being presented at the American Physiological Society (APS) “Aldosterone and ENaC in Health and Disease: The Kidney and Beyond Conference” in Estes Park, Colorado.
Rostyslav Bubnov, PhD, of the Zabolotny Institute of Microbiology and Virology, National Academy of Sciences of Ukraine, and first author of the study, whith his team studied the effects of probiotic therapy on adults with obesity, gout and gout-related kidney disease. Past research suggests that probiotics decrease inflammation in the body and improve poor sugar and uric acid metabolism that contribute to the development of gout. The type of probiotics prescribed was personalized to each volunteer based on his or her symptoms. The researchers administered the standard minimum probiotic recommended dosage (100 million colony-forming units). After 10 days of probiotic therapy, the volunteers’ health improved. They experienced lower blood pressure, reduced abdominal fat with weight loss, normal uric acid and creatinine levels in the blood along with lesser tophi size. Beside, ecography approach detected decreased lesion size and scar tissue on the kidneys. The team believs that individualized probiotic therapy (with over-the-counter supplements and yogurt) is effective to treat hyperuricemia and can successfully restore function and structure of the damaged kidney in gout.
Gout therapy usually uses inhibitors of xanthine oxidase, the historical prototype being allopurinol, a derivative of inosine. Treatment with two common FDA-approved gout medications have been found to cause rapid death to the parasites that cause elephantiasis. Researchers at the Uniformed Services University (USU) have discovered that sulfinpyrazone and probenecid, two old drugs used regularly for gout, have a lethal effect in vitro on the parasitic worms that cause lymphatic filariasis. This disease is a highly prevalent and morbid roundworm infection that is present throughout the tropics. The infection causes genital and lower extremity swelling that, in its most severe form, is called elephantiasis. Current global efforts to eradicate lymphatic filariasis are limited by a lack of medications that can kill the adult stages of the worm when given as a short course. Using the molecular approach called siRNA inhibition, by which scientists can stop the production of one protein at a time, Dr. Alexander Flynn and colleagues at USU identified the enzyme (UDP-glucuronosyltransferase, UDPGT) within the intestinal tract of filarial worms as being essential for adult worm survival.
A similar result was obtained by another team in 2014, with the discovery that this same enzyme was essential fo the parasite Haemonchus contortus (barber’s pole worm) to be resistant to against the drug naphtalophos. Indeed, enhanced killing of the worm was seen if naphtalphos was co-administered with UDPGT inhibitors like 5-nitrouracyle, probenecid and sulpfinpyrazone. Because these gout medications are generic and are generally safe (probenecid is a pregnancy category B drug, which is the same as penicillin), they may be able to kill the adult stages in infected people. Army Major Alexander Flynn, Chief of the Microbiology Hub Kericho, Medical Research Directorate – Africa/Kenya believes that if studies in humans show an ability of these medications to kill adult filarial worms, this discovery could accelerate efforts to eliminate lymphatic filariasis: He commented: “This study suggests that probenecid and sulfinpyrazone, two generally safe medications that have been long-used for gout, may be able to kill adult filarial parasites in infected individuals. If future studies show efficacy in pre-clinical and clinical studies, this discovery could help global efforts to eliminate elephantiasis.”
Another (for sure not the last) example of drug repurposing that will accelarate clinical trials allowing to waste precious time, resources and lives.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialista in Biochimica Clinica.
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