New Drugs to Treat Gout Coming Soon

by Thilaka Ravi on  March 20, 2013 at 7:51 AM Drug News   - G J E 4
Development of new drugs to treat gout, a painful inflammation that results from a buildup of uric acid around joints, could emerge from findings following a recently published Loyola University Chicago Stritch School of Medicine study.
New Drugs to Treat Gout Coming Soon
New Drugs to Treat Gout Coming Soon

The study, led by Liang Qiao, MD, and his colleagues and collaborators, was published March 19 in the journal Nature Communications.

Gout is caused by a buildup of uric acid around joints, typically the big toe, knee or ankles. The immune system revs up to attack uric acid salt crystals, and this immune response causes painful inflammation.

The innate immune response is mainly activated by calcium that enters a macrophage immune cell through an opening called the calcium channel. There are several types of calcium channels. Researchers found that a particular type of calcium channel, called TRPM2, is responsible for initiating the immune response. (TRPM2 stands for transient receptor potential melastatin 2.)

In lab mice, study collaborators from Japan knocked out a gene that is responsible for this calcium channel. Qiao's team then exposed these "knockout" mice and a comparison group of normal mice to uric acid salt crystals and to a liposome, a compound that also causes inflammation. They found that inflammation was significantly lower in the knockout mice that lacked the TRPM2 calcium channel. They therefore concluded that disabling the TRPM2 calcium channel could be key to reducing painful inflammation from gout.

The next step will be to design a compound that would block the TRPM2 calcium channel, and then test how well this compound reduces inflammation in an animal model.

The study's findings might also apply to Alzheimer's disease and arteriosclerosis (hardening of the arteries). These two diseases, like gout, have been linked to inflammation. And it is possible that the TRPM2 calcium channel may be key to initiating the inflammatory response in these two diseases as well. But this has not been proven yet, Qiao said.

The study also could aid in the development of new vaccines. Researchers elsewhere are studying whether liposomes could serve as more effective adjuvants in new vaccines. (An adjuvant is the component in a vaccine that stimulates the immune system to attack a pathogen such as a virus or bacterium). The Loyola study found that only liposomes with either a positive or a negative electric charge are effective in stimulating the immune system.

Liposomes with a neutral charge did not stimulate the immune system.

Qiao, senior author of the study, is a professor in the Department of Microbiology and Immunology at Loyola University Chicago Stritch School of Medicine. Co-authors of the study are Zhenyu Zhong (first author, significant contributor), Yougang Zhai, Shuang Liang and Renzhi Han, all of Loyola University Chicago; Yasou Mori of Kyoto University in Japan; and Fayyaz S. Sutterwala of the University of Iowa.

Source: Eurekalert

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One of the arthritic diseases is gout in which sodium urate crystals are deposited in cartilage, especially in the feet. 90% of victims are men, perhaps because men are more likely to come in contact with lead, a kidney poison. The crystals are thought to be ingested by white blood cells and produce inflammation by rupture of the lysosome sacs and release of their contents Urate is the major end product of purine [nucleoproteins] degradation in higher primates in contrast to most other mammals because of the genetic silencing of hepatic oxidative enzyme uricase. The kidney plays the dominant role in urate excretion, with the intestines accounting for about one third as much. Lin has statistical evidence linking gout to lead poisoning. The lead poisoning makes the aldosterone system insensitive to potassium concentration and increases the potassium content of the blood plasma. The blood lead content is no indicator of toxicity and the status must be obtained with an EDTA mobilization test. Lead level in the body is significantly correlated with urate excretion and gout. Ethylenediaminetetraacetic acid chelator of lead has successfully increased uric acid excretion. Fluoride increase lead intake. Other poisons than lead may move one a little closer to gout also, such as timalol combined with hydrochlorothiazide and amiloride (a diuretic. I also suspect that toluol or some other chemical in acrylic automobile enamel may be able to trigger gout. I have heard of a doctor who gave his patients potassium losing diuretics and thus triggered an attack of gout. By adding a potassium supplement he was able to remove the gout. A medical doctor has used potassium supplements for gout. Gout can be triggered by the same agents that cause potassium losses such as fasting, surgery, and potassium losing diuretics [Rodman]. A potassium deficiency can increase urate levels in the blood [Davis] Urate kidney stones form during gout in a 10-30% of cases [Colton]. Making the urine less acid with potassium citrate or sodium bicarbonate is a current treatment for kidney stones [Shekarriz] [Rodman]. Potassium citrate has been successfully used to eliminate urate stones and sodium bicarbonate did not prevent their formation [Pak]. I have rapidly removed gout symptoms by large potassium bicarbonate supplements several times. Potassium bicarbonate may be obtained from organizations selling it as a wine additive.
isoptera Monday, July 15, 2013

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