-eh-known, trade names Catena
, among others) is a drug
that was initially developed by Takeda Pharmaceutical Company
for the treatment of Alzheimer's disease
and other cognitive
defects. This has been met with limited success. The Swiss company Santhera Pharmaceuticals
has started to investigate it for the treatment of neuromuscular diseases
. In 2010, early clinical trial
s for the treatment of Friedreich's ataxia
and Duchenne muscular dystrophy
have been completed. the drug is not approved for these indications in North America or Europe, but it is approved for the treatment of Leber's hereditary optic neuropathy
(LHON) in Europe.
Chemically, idebenone is an organic compound
of the quinone
family. It is also promoted commercially as a synthetic analog
of coenzyme Q10
Indications that are or were approved in some territories
Nootropic effects and Alzheimer's disease
Idebenone improved learning and memory in experiments with mice. In humans, evaluation of Surrogate endpoint
s like electroretinography
, auditory evoked potential
s and visual analogue scale
s also suggested positive nootropic
effects, but larger studies with hard endpoints are missing.
Research on idebenone as a potential therapy of Alzheimer's disease
have been inconsistent, but there may be a trend for a slight benefit. In May 1998, the approval for this indication was cancelled in Japan due to the lack of proven effects. In some European countries, the drug is available for the treatment of individual patients in special cases.
Friedreich's ataxia (Sovrima)
Preliminary testing has been done in humans and found idebenone to be a safe treatment for Friedreich's ataxia (FA), exhibiting a positive effect on cardiac hypertrophy
and neurological function. The latter was only significantly improved in young patients. In a different experiment, a one-year test on eight patients, idebenone reduced the rate of deterioration of cardiac function, but without halting the progression of ataxia
The drug was approved for FA in Canada in 2008 under conditions including proof of efficacy in further clinical trials. However, on February 27, 2013, Health Canada announced that idebenone would be voluntarily recalled as of April 30, 2013 by its Canadian manufacturer, Santhera Pharmaceuticals, due to the failure of the drug to show efficacy in the further clinical trials that were conducted. Voluntary Withdrawal of Catena from the Canadian Market
In 2008, the European Medicines Agency
(EMA) refused a marketing authorisation for this indication. As of 2013 the drug was not approved for FA in EuropeMargaret Wahl for Quest Magazine, MAY 28, 2010. FA Research: Idebenone Strikes Out Again
nor in the US, where there is no approved treatment. NINDS Fact Sheet
Indications being explored
Duchenne muscular dystrophy (Catena)
After experiments in mice and preliminary studies in humans, idebenone has entered Phase II clinical trials in 2005 and Phase III trials in 2009.
Leber's hereditary optic neuropathy (Raxone)
Leber's hereditary optic neuropathy
(LHON) is a mitochondrially inherited (mother to all offspring) degeneration of retinal ganglion cells (RGCs) and their axons that leads to an acute or subacute loss of central vision; this affects predominantly young adult males. Santhera completed a Phase III clinical trial in this indication in Europe with positive results, and submitted an application to market the drug to European regulators in July 2011. In January 2013, the request for marketing authorisation was refused by the EMA.
Other neuromuscular diseases
Phase I and II clinical trials for the treatment of MELAS
(mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes) and primary progressive multiple sclerosis
are ongoing .
Idebenone is claimed to have properties similar to CoQ10 in its antioxidant
properties, and has therefore been used in anti-aging
on the basis of free-radical theory
. Clinical evidence for this use is missing. It has been used in topical
applications to treat wrinkle
In cellular and tissue models, idebenone acts as a transporter in the electron transport chain
and thus increases the production of adenosine triphosphate
(ATP) which is the main energy source for cells, and also inhibits lipoperoxide
formation. Positive effects on the energy household of mitochondria has also been observed in animal models. Clinical relevance of these findings has not been established.
Idebenone is well absorbed from the gut but undergoes excessive first pass
metabolism in the liver, so that less than 1% reach the circulation. This rate can be improved with special formulations ( suspension
s) of idebenone and by administering it together with fat food; but even taking these measures bioavailability
still seems to be considerably less than 14% in humans. More than 99% of the circulating drug are bound to plasma protein
s. Idebenone metabolites include glucuronide
s and sulfate
s, which are mainly (~80%) excreted via the urine.