Gout
Gout is a complex form of arthritis characterized by the deposition of urate crystals in the joints and surrounding tissues. Our company is at the forefront of gout drug and therapy development services, offering innovative solutions to tackle this debilitating disease.
Introduction to Gout
Gout is a type of inflammatory arthritis caused by the accumulation of uric acid in the body. Uric acid is a byproduct of purine metabolism, and when its levels become elevated, it can lead to the formation of urate crystals. These crystals trigger an immune response, resulting in the characteristic symptoms of gout, including intense joint pain, swelling, redness, and heat.
- Elevated levels of uric acid can arise from various factors, including overproduction or underexcretion. The enzyme xanthine oxidase plays a vital role in the production of uric acid by converting hypoxanthine and xanthine into uric acid. Therefore, targeting xanthine oxidase represents a promising strategy for gout therapeutics.
- Another target of interest is the urate transporter URAT1, responsible for the reabsorption of uric acid in the kidneys. Inhibiting URAT1 can enhance uric acid excretion, thereby reducing its levels in the body. Additionally, pro-inflammatory cytokines, such as interleukin-1 beta (IL-1β), have been implicated in gout pathogenesis, making them potential targets for therapy development.
Fig.1 Therapeutic strategies for gout. (Pillinger M. H., et al., 2020)
Drug Discovery and Development for Gout
Small molecule drugs have long been the mainstay of gout treatment. A notable example is febuxostat, which acts as a selective inhibitor of xanthine oxidase. By inhibiting this key enzyme involved in uric acid production, febuxostat effectively lowers serum urate levels. Additionally, targeted therapies have emerged as a promising avenue for managing gout. Biologic agents, like pegloticase, offer a focused mechanism of action by directly degrading uric acid. Pegloticase is a recombinant uricase enzyme that converts uric acid into a more soluble compound called allantoin. As a result, the body can easily eliminate the excess uric acid.
Our company is actively involved in the development of novel therapies for gout. Our dedicated team of researchers and scientists work tirelessly to identify new targets, develop small molecule drugs, and explore innovative approaches for targeted therapy development. To learn more about how we can assist you, please click the links below.
Our Services
At our company, we are committed to advancing gout diagnostics and therapy development. Our state-of-the-art diagnostic development services enable accurate and timely identification of gout, facilitating early drug screening and therapeutic development.
Through meticulous breeding and phenotyping, we develop animal models that mimic key aspects of gout, including hyperuricemia, crystal deposition, and joint inflammation. These models enable researchers to gain valuable insights into disease mechanisms, test the efficacy of drug candidates, and assess their safety profiles before advancing to clinical trials.
Animal Models
A prominent animal model offered by our company is the potassium oxylate-induced hyperuricemia model. Potassium oxonate, a uricase inhibitor, is administered to rodents to mimic hyperuricemia observed in humans. By inhibiting the uricase enzyme, which converts uric acid into a more soluble compound for excretion, potassium oxonate increases uric acid levels.
At our company, we also offer a combination model that combines the potassium oxonate-induced hyperuricemic model with the MSU crystals-induced gouty arthritis animal model. This model enables researchers to assess both hyperuricemia and inflammation parameters simultaneously, providing a comprehensive understanding of the disease.
Another valuable service offered by our company is the MSU crystals-induced gouty arthritis animal model. Monosodium urate (MSU) crystals play a pivotal role in the development of gout. In this model, MSU crystals are injected into the joints of animals, leading to an inflammatory response resembling gouty arthritis.
Understanding the impact of diet on hyperuricemia is crucial in gout research. Our company's diet-induced hyperuricemia model provides a valuable tool for investigating the effects of a high-purine diet on the development of hyperuricemia. Mice are fed a diet rich in purine-containing foods, such as animal meats and seafood, to induce hyperuricemia.
In Vitro Models
One of the key services provided by our company is the development of a monosodium urate crystals (MSU)-induced oxidative stress model. In this model, monocytes are exposed to MSU crystals to induce oxidative stress and evaluate the effects of potential therapies. The intracellular production of reactive oxygen species (ROS), a hallmark of oxidative stress, is measured to assess the antioxidant properties of test compounds.
Our preclinical research services encompass a wide range of evaluations, including pharmacokinetics, pharmacodynamics, and toxicity studies, ensuring that potential therapies meet the highest standards of safety and efficacy. In addition to the services and models listed above, we also provide customized services and disease model development services to meet your specific needs. If you are interested in our services, please don't hesitate to contact us.
Reference
- Pillinger M. H., and Mandell B.F., "Therapeutic approaches in the treatment of gout." Seminars in Arthritis and Rheumatism. Vol. 50. No. 3. WB Saunders, 2020.