I-3 Treatment of CPT2 deficiency with bezafibrate

Other potential modes of metabolic therapy include: 1.Supplementation of the missing compound, e.g. CoQ10 which is effective only in primary Q10 deficiency and is given to most patients with mitochondrial disorders even if deficiency is not tested; 2. Pharmacologically increasing the oxidative capacity of muscle (by giving various ‘cocktails’ of oxygen species scavengers that include: carnitine, vitamin C, riboflavin, and extra creatine); 3. Changing the diet composition in order to increase the availability of compensatory fuel sources (e.g. sucrose or a carbohydrate rich diet given before exercise in MacArdle’s disease). Because of the rarity of metabolic myopathies no proper double blind studies were performed to assess these therapeutic modalities. Hereditary inclusion body myopathy (HIBM) is a destructive muscle disease due to mutations in GNE, an enzyme in the synthetic pathway of sialic acid. Part of the pathogenic mechanism is thought to be sialylation deficiency so correcting it may affect the disease course. Providing orally a metabolic intermediate that is downstream to the defective site in the sialic acid pathway (e.g. ManNac) or sialic acid itself was shown to be effective in a mouse model of HIBM. With these considerations in mind, planned therapy of this progressive metabolic myopathy is now reaching human trials. Human and animal toxicity studies with various compounds are now in progress.