DWQA QuestionsCategory: QuestionsDifference between bezafibrate and REN 001
Ann asked 3 years ago
Could you explain the difference between the mechanisms of action of REN 001 and bezafibrate in the treatment of LC-FAOD, in relation to their specificity on PPAR receptors?
Thank you in advance
replied 3 years ago

Ann, Contol of genes is accomplished through specialized DNA signals called a promotor. This squeeze recognizes equally specialized proteins that turn on all genes controlled by a promotor. Many drugs and non-medical chemicals have developed to mimic the action of those proteins and thus turn on the same set of genes. One such promotor goes by the initials PPAR, but it has several variations identified by Greek letters (alpha, delta, gamma) that respond to a different extent to each of these chemicals. Most of the genes involved in mitochondrial energy metabolism, including fatty acid oxidation are controlled by the PPAR delta promotor. Bezafibrate is a drug that has a relatively broad action and stimulates all of the PPAR promotors to some extent. This has the effect of increasing the production of fatty acid oxidation proteins, but the effect is limited because as the dose is increased, other unwanted actions also occur. As a result, the clinical efficacy of this drug has been limited in clinical trials studying it’s use in fatty acid oxidation disorders. REN-001 is much more specific for PPAR delta and therefore has a much larger effect on energy genes, including fatty acid oxidation, then bezafibrate. Thus, it should, in theory, be more effective than bezafibrate to treat fatty acid oxidation disorders. Indeed my lab has reported such an effect in cells form patients with fatty acid oxidation disorders at the annual INFORM meeting. REN001 is now in clinical trials to see if this difference translates into clinical improvement in patients. Anyone interested in participation in the trial can check the details and participating sites at clinicaltrials.gov. Hope this helps. Dr. Vockley