Ranirestat (also known as AS-3201) is an
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 ...
being developed for the treatment of
diabetic neuropathy
Diabetic neuropathy is various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic c ...
by
Dainippon Sumitomo Pharma
is a pharmaceutical company based in Japan. Its headquarters are in Chuo-ku, Osaka.
The original Dainippon Pharmaceuticals (Dainippon Seiyaku) was established in 1885 by Nagayo Sensai, a graduate of Tekijuku – the first private medical school ...
and
PharmaKyorin. It has been granted
orphan drug
An orphan drug is a pharmaceutical agent developed to treat medical conditions which, because they are so rare, would not be profitable to produce without government assistance. The conditions are referred to as orphan diseases.
The assignment of ...
status. The drug is to be used orally.
Trials
A Canadian Phase III
clinical trial
Clinical trials are prospective biomedical or behavioral research studies on human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel vaccines, drugs, dietar ...
has been completed. Phase III trials in Europe and the US started 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
In organic chemistry, a polyol is an organic compound containing multiple hydroxyl groups (). The term "polyol" can have slightly different meanings depending on whether it is used in food science or polymer chemistry. Polyols containing two, thr ...
) 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 (INN) (AY-27773) 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 an ...
, also an aldose reductase inhibitor, which was withdrawn from market in 1997 due to the risk of severe liver toxicity
References
Aldose reductase inhibitors
Orphan drugs
Pyrrolopyrazines
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