Ranirestat is an aldose reductase inhibitor

Aldose reductase inhibitor

Aldose reductase inhibitors are a class of drugs being studied as a way to prevent eye and nerve damage in people with diabetes.-Mechanism:Their target, aldose reductase, is an enzyme that is normally present in many other parts of the body, and catalyzes one of the steps in the sorbitol pathway...

 being developed for the treatment of diabetic neuropathy

Diabetic neuropathy

Diabetic neuropathies are neuropathic disorders that are associated with diabetes mellitus. These conditions are thought to result from diabetic microvascular injury involving small blood vessels that supply nerves in addition to macrovascular conditions that can culminate in diabetic neuropathy...

 by Dainippon Sumitomo Pharma

Dainippon Sumitomo Pharma

is a pharmaceutical company based in Japan.The original Dainippon Pharmaceuticals was established in 1885 by Nagayo Sensai, a graduate of Tekijuku – the first private medical school in Japan established by Ogata Kōan. It was set up as a wholly private company invested by a number of people in...

 and PharmaKyorin. It has been granted orphan drug

Orphan drug

An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...

 status. The drug is to be used orally.

Trials

A Canadian Phase III clinical trial

Clinical trial

Clinical trials are a set of procedures in medical research and drug development that are conducted to allow safety and efficacy data to be collected for health interventions...

 has been completed. Phase III trials in Europe and the US started in in June 2009 and are expected to complete in April 2013.

Mechanism of action

Ranirestat is aldose reductase inhibitor that acts by reducing sorbitol accumulation in cells. Aldose reductase is an enzyme that catalyzes one of the steps in sorbitol (polyol

Polyol

A polyol is an alcohol containing multiple hydroxyl groups. In two technological disciplines the term "polyol" has a special meaning: food science and polymer chemistry.- Polyols in food science :...

) pathway which is responsible for formation of fructose from glucose. Aldose reductase activity is increased, parallel to glucose blood levels, in tissues that are not insulin sensitive, including lenses, peripheral nerves and renal glomeruli. Sorbitol does not diffuse through cell membranes easily and therefore accumulates in these tissues, causing osmotic damage, leading to retinopathy and neuropathy.

Efficacy

Results from a Canadian double-blind, placebo-controlled biopsy Phase III clinical trial, involving total of 549 patients with diabetic sensorimotor polyneuropathy (DSP) randomly assigned to treatment with placebo or 10, 20, or 40 mg/day ranirestat for 52 weeks, showed that ranirestat appears to have effect on motor nerve function in mild to moderate DSP, but failed to show statistically significant difference in sensory nerve function. Efficacy of ranirestat was evaluated by nerve conduction studies, the modified Toronto Clinical Neuropathy Score (mTCNS), and quantitative sensory tests (QSTs).

See also

• Tolrestat
  Tolrestat
  Tolrestat is an aldose reductase inhibitor which was approved for the control of certain diabetic complications.While it was approved for marketed in several countries, it failed a Phase III trial in the U.S. due to toxicity and never received FDA approval. It was discontinued by Wyeth in 1997...
  
  , also a aldose reductase inhibitor, which was withdrawn from market in 1997 due to the risk of severe liver toxicity