GOUT Disease and New Research Treatment

Gout is chronic ancient and painful disease usually affecting the big toe or joints of the instep, ankles, heels, knees, wrists, fingers and elbows, primarily more men than women. 1 In the United States, estimated two million to three million people have gout. 3 Gout is attributed to an increase in Uric acid in the body. Many foods contain a high or low concentration of substance called purines. In the human body, purines breakdown to form uric acid (Except in mammals an enzyme called uricase breaks down purines, then are easily removed from the body. 7)."Normally, uric acid is dissolved in the blood and passed through the kidneys into the urine, where it is eliminated." 2 Any excess amount of uric acid is passed through the intestines, where bacteria works to break it down. 7 When the kidneys do not eliminate the uric acid as result of abnormal concentration in the blood (hyperuicemia), sodium monourate crystals form and accumulate in joint fluid and joint coverings leading to inflammation or swelling (pain) known as gout.(Normal concentration of uric acid is below 6.8 mg/dL (miligrams/deciliter) compared to abnormal concentration level above 7 mg/dL. 7). 1 Most common acid crystal deposits formulate in the big toe, causing pain, swelling, redness and stiffness, besides other joint locations. "Gout occurs in 8.4 of every 1,000 people." Underneath the skin appears as lumps or accumulation of deposits of uric acid (called tophi). Also, uric acid crystals can accumulate in the kidneys. 2

Gout is attributed by one of many factors, but certainly eating more high-purine foods (liver, mushroom, beef (fillet) fish (sardines in oil, and tuna), and crispbread 4) compared to eating less prine foods such as vegetables (broccoli, spinach, potatoes, carrots, etc 4) contribute to lower uric acid level, manageable for the kidneys to eliminate. 2 Also, other related causes of gout include stressful events, hereditary connection, ("Twenty percent of people with gout have a family history of the disease".), more common in men than women (More frequently among men between 40 - 50 years old. Women primarily after menopause develop signs and symptoms of gout.5), Increase weight risks developing gout, excessive alcoholic consumption, exposure to lead in the environment, and health related problems including renal failure or insufficiency (Common in older people when kidneys are unable to eliminate waste products), high blood pressure, Kelley-Seegmiller syndrome or Lesch-Nyhan syndrome (Elimination or insufficient quantity of enzyme which controls the level of uric acid), and taking medications that increase uric acid (Aspirin, diuretics, nicotine acid (niacin), levodopa (Larodopa) and cyclosporine (Sandimmune, Neoral - "a medication that suppresses the body's immune system".)). Organ transplant patients are more likely to be susceptible to this disease. When painful episodes of gout occur is usually experienced for three to ten days without treatment. "The next attack may not occur for months or even years. 2

Diagnosis of gout is confirmed through an invasive procedure that extracts fluid from an affected joint through a needle and examined under a microscope for the presences of monosodium urate crystals. Blood test for gout is often inaccurate, because in a healthy person who does not have gout may indicate elevated levels of Uric acid. 6 Those that have arthritis, five percent of cases attributed to gout. The disease has four stages of development. Least non symptomatic has elevated levels of uric acid in the blood requiring no treatment and worst stage is chronic tophaceous gout which is most debilitating, sustainable perhaps longer than ten years, permanent kidney and joint damage but fortunately most people have received treatment before reaching this severe stage. 2

Currently medications is available to treat gout (Such as generic colchicine, and Non-steroidal anti-flmammatory drugs such as "aspirin like". 6 Also prescribed Zyloprim which controls the rate the body produces uric acid 2.), however must be tailored according to each patient tolerance for side effects and medical conditions including impaired kidney function, ulcer disease or use of blood thinners. Besides proper diet and elimination / reduction of drinking alcohol is recommended. Also, adjusting or changing medications can alter the painful symptoms of gout. Gout is forcibly controllable if strict life style changes are adhered too. 6

Being evaluated (October 2008) in a phase three human trial study, Savient Pharmaceuticals (Public trading company on the NASDAQ Exchange - SVNT 11) drug pegloticase, treat serious cases of gout. 8 Pegloticase is the newest drug to treat chronic gout in the past forty years. 12 The new drug has shown to lower the level of uric acid among patients who have received the intravenous pegloticase injection within six hours. In 2008, researchers informed those attending the American College of Rheumatolgoy in San Francisco, a research study confirmed pegloticase kept levels of uric acid down at least six months in forty percent of patients. 8 The research study participants were mostly men average age fifty-five. Those in the group study who were administered more frequently (four times a week) eight milligrams of pegloticase experienced the greatest improvement in their disease and improved physical function (9): Including being able to wear normal shoes and use their fingers normally again. 12

Lead Investigator Dr. John S. Sundy, an associate professor of medicine at Duke University Medical Center said (published in American College of Rheumatolgy news release): "Therefore, these findings are exciting, because they show that pegloticase was able to reduce urate levels and improve clinical outcomes in subjects with gout who had exhausted all available treatment options." 9 Pegloticase compared to current drug treatment allopurinol ("a drug that decreases the production of urate by inhibiting another enzyme, xanthine oxidase." 12) to treat gout, about 500,000 gout patients in the United States would likely benefit from this new drug treatment, unable to tolerate (up to five percent 12) or respond well to current treatment (8), including life threatening adverse reaction. 12

Several financial analysts on Wall Street are concerned Pegloticase may not get Food and Drug Administration approval for sale and distribution expected in 2009. The concern cardiovascular adverse side effects of Pegloticase seen during the development stages of the drug and clinical evaluation may complicate the risk reward outcome. During clinical evaluation program of Pegloticase reported seven deaths attributed to heart-related issues, however according to Savient Pharmaceuticals does not believe deaths are drug related. Savient said in a statement: "The emerging safety profile of long-term pegloticase (Puricase) therapy is consistent with that observed in the six month double-blind studies, who no apparent new safety concerns related to long-term exposure." 10

References:

1.) What is Gout? - http://www.allaboutarthritis.com/AllAboutArthritis/layoutTemplates/html/en/contentdisplay/document.jsp?docID=condition/arthritis/clinicalArticle/gout_what_is_it.xml

2) Gout, Causes, Diagnosis and Treatment - http://www.news-medical.net/encyclopedia/Gout_Causes_Diagnosis_Treatments

3.) New drug may treat gout, U.S. researchers find - http://www.reuters.com/article/healthNews/idUSTRE49P2ID20081026?feedType=RSS&feedName=healthNews

4.) Which Foods are Low in Purines - http://www.gout-diet-tips.com/foods_high_in_purines/

5.) BONES JOINTS AND MUSCLES - http://www.mayoclinic.com/health/gout/DS00090/DSECTION=risk-factors

6.) GOUT - http://www.rheumatology.org/public/factsheets/diseases_and_conditions/gout.asp?aud=pat

7.) Gout - http://www.umm.edu/patiented/articles/what_gout_000093_1.htm

8.) New drug may treat gout, U.S. researchers find - http://www.reuters.com/article/healthNews/idUSTRE49P2ID20081026?feedType=RSS&feedName=healthNews

9.) Drug Improves Outcome for Gout Patients - http://www.healthscout.com/news/1/620653/main.html

10.) AP Savient shares fall over gout drug safety concerns - http://biz.yahoo.com/ap/081027/savient_mover.html?.v=1

11.) SAVIENT PHARMACEUTICALS, INC - http://www.savientpharma.com/

12.) Puricase, First New Drug Treatment Approach for Gout in 40 Years, Could Potentially Revolutionise Treatment for Some - http://www.medicalnewstoday.com/articles/47230.php