Temsirolimus, designated Orphan Drug for the treatment of adrenoleukodystrophy
CIBERER | Wednesday, June 15, 2016
The European Medicines Agency (EMA) has appointed a molecule, Temsirolimus, as an orphan drug for the treatment of adrenoleukodystrophy, a rare disease neurometabolic origin that affects the nervous system and the adrenal glands manifestations of varying severity that can reach be fatal. Temsirolimus is a molecule that prevents power failure and slows progression of motor deficits in animal models of X-linked adrenoleukodystrophy, which could be useful for the treatment of patients affected by this disorder.
Studies on the possible application of this orphan drug for the treatment of X-adrenoleukodystrophy, which have so far limited to animal models of disease medicine, have been developed by the U759 CIBERER led by Dr. Aurora Pujol in the IDIBELL of U721 Barcelona and led by Dr. Erwin Knecht in the IPPC Valencia. This orphan medicinal product is sponsored by the CIBER.
Temsirolimus is a molecule that inhibits the activity of an enzyme, the target of rapamycin in mammalian cells (mTOR), involved in the negative control of autophagy. Autophagy is one of the mechanisms of self-protection of stressed cells used to resolve difficult situations, eliminating altered components, generating energy and cell metabolism adapting to each situation. Temsirolimus can activate autophagy, which is inhibited in adrenoleukodystrophy, so that the accumulation of oxidized proteins, energy failure and other disturbances that are important in the progression of this disease are avoided, and contributes to that slow down the progression of axonal degeneration and associated motor deficits.
Adrenoleukodystrophy, also known as adrenoleukodystrophy with linkage to X (X-ALD) chromosome is a neurometabolic disorder inheritance linkage to X recessive, caused by mutations in the gene ABCD1 . It affects mostly men, although some women carriers can have milder forms of the disease. Adrenoleukodystrophy has in Europe an estimated prevalence of 0.35 people per 10,000 population.
This condition causes the accumulation of fatty acids of very long chain, especially in the nervous system and the adrenal glands. This disrupts normal cellular activity in these body parts.
There are three different types of the disease with varying degrees of severity. The most severe, infantile cerebral adrenoleukodystrophy, affects only children and is associated with behavioral disorders such as inattention or hyperactivity. The disease is degenerative brain destroying myelin and leads to suffer quadriplegia and dementia. Since the manifestation of the disease, its progression is usually rapid and leads to the death of children between 5 and 10 years old. In the second form, adrenomyeloneuropathy, symptoms appear between 20 and 30 years. Patients have stiffness and spasticity in the legs, and slowly progresses to leave patients unable wheelchair. The milder form of the disease presents with primary adrenocortical insufficiency, although almost all patients develop neurological symptoms as adults. The risks of disease are chronic weakness and even death by demyelination.
Benefits of orphan designation
The designation as an orphan drug by the EMA has advantages such as receiving a marketing authorization for 10 years that can not be marketed similar products, power available protocols and complimentary scientific council or at a reduced cost, and exemption from payment for designation. In addition, entities that develop orphan drugs have access to specific EU subsidies and programs of member states