PPARα receptors were identified as potential targets for pharmacological therapy of CPTII and VLCAD deficiencies. PPARα is a transcription factor, belonging to the superfamily of steroid-thyroid hormone receptors, which is able to modify CPT2 and VLCAD gene expression (Lemberger et al, 1996). Djouadi et al. established that administration to control mice of a CPT I inhibitor (etomoxir) causes a feedback induction of PPARα target genes involved in fatty acid oxidation such as medium-chain acyl-CoA dehydrogenase and acyl-CoA oxidase genes (Djouadi et al, 1998). PPARα was also shown to regulate the constitutive expression of the CPT2 gene and protein in the adult mouse heart and liver and to mediate up-regulation of CPT2 gene in response to fibrates in mouse liver (Aoyama et al, 1998, Watanabe et al, 2000). In humans, the "fibrate" class of hypolipidaemic drugs (clofibrate, bezafibrate, gemfibrozil, etc…) are specific ligands of PPARα and the interaction with PPARα forms the molecular basis of therapeutic effects of these drugs (Vamecq et al, 1999). The research group of Bastin J and Djouadi F hypothesized that the hypolipidemic drug bezafibrate, acting as an activator of PPARα, might stimulate FAO in CPT II and VLCAD-deficient cell lines. Bezafibrate treatment of fibroblasts from four CPT II-deficient patients with the "adult" form of the disease was shown 1) to increase the amount of CPT2 mRNA (+ 47 % to + 66 %) and the residual CPT II enzyme activity (+ 54 % to + 135 %) in a time- and dose-dependant manner, and 2) to normalize 3H-palmitate and 3H-myristate oxidation rates. Conversely, bezafibrate did not correct FAO in two patients with the "infantile" form of CPTII deficiency (Djouadi et al, 2003). Since the clinical expression of the "adult" form of CPT2 deficiency is restricted to skeletal muscle, the effect of fibrates was tested on FAO in muscle samples from such patients. After being provided with muscle samples from patients with the "adult" form of CPTII deficiency followed at the Institute of Myology (P. Laforêt, B. Eymard), it has been shown that myoblasts from these biopsies exhibited a 40 % decrease in FAO compared to control cells (Djouadi et al, 2003). Moreover, pretreatment of CPTII-deficient myoblasts with bezafibrate restored FAO to normal levels (Bastin et al, 2003).