Targeting Urate Transporters & Uricase

What is the connection between hyperuricemia and the development of various diseases?

Why Gout?

Humans and other higher primates lack/lost the enzyme, Uricase, which would otherwise have broken down Uric Acid to water-soluble, easily-excretable Allantoin.

Couple this with a set of highly conserved genes coding for a host of urate transporters at our kidneys and intestines, the majority of which are hell-bent to reabsorb rather than to excrete uric acid, the default position is to accumulate uric acid. As such, the main cause of Gout is the under-excretion of uric acid rather than its over-production.

So, developing Gout is mainly genetic. Which means dietary manipulation alone is not likely to "cure" Gout. The fact is, no more than a third of our daily uric acid production is from what we consume. Nevertheless, diet still plays a role, given that humans are the only uricase-deficient primates to develop spontaneous Gout. And a high sugar (fructose especially) diet appears to be most incriminating.

Going forward, new therapeutics focusing on "draining the swamp" should prove more effective in the treatment of Gout, especially if we are unable to modify our lifestyle to reduce toxic dumping.

Pharmacodynamic and Pharmacokinetic Study of Verinurad in Adult Male Subjects with Mild, Moderate, and Severe Renal Impairment: A Phase 1, Open-Label Study

Background/Purpose: Verinurad (RDEA3170) is a high-affinity, selective URAT1 inhibitor in development for the treatment of gout and asymptomatic hyperuricemia. This Phase 1, single-dose, open-label study investigated the pharmacodynamics (PD), pharmacokinetics (PK), and safety of oral verinurad in a...

Selecta Biosciences, Inc. (NASDAQ SELB), a clinical-stage biopharmaceutical company developing a novel class of targeted antigen-specific immune therapies, toda

When the need arises to reduce serum uric acid rapidly, such as in impending acute kidney failure or when all-else-fails, only Uricase can cut it.

Unfortunately, as this enzyme is commercially derived by recombinant DNA technology from non-human sources, it is immunogenic, which will eventually render it ineffective or allergenic.

Will pegylating it (coating a drug to confer "stealth") and combining it with an immune-dampening drug help?

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