From molecular to clinical bases in neurometabolic illnesses

Mitochondrions are the factories that produce the energy (ATP) that our cells need to function, and also most of the free radicals (ROS) that can destroy these cells if they are not properly neutralised. In the most common neurodegenerative diseases, such as Alzheimer's, Parkinson's and multiple sclerosis, defects in mitochondrial function have been found to be linked with the degeneration of axons. In our laboratory we are currently researching the interrelation of the two factors in a rat model of adrenoleukodystrophy, a rare disease of the nervous system caused by the loss of function by a fatty acid transporter from the peroxisome. We have demonstrated that these fatty acids are harmful to mitochondrions, and end up damaging axons. Several preclinical tests with antioxidants and mitochondrial protectors have proved effective, by compensating for the oxidative damage, mitochondrial function and energy deficiency, as well as the axonal damage and associated motor deficit. We have translated these results into two pioneering phase II clinical tests for adrenoleukodystrophy patients; these tests are currently in progress and may have implications for the most common degenerative diseases that use altered metabolic channels.