Nrf2 is decreased in FRDA cells. PTC-743 (formerly EPI-743) is being developed by PTC Therapeutics. PTC-743 is a para-benzoquinone and targets the NAD(P)H dehydrogenase (quinone 1) (NQO1) enzyme to increase the biosynthesis of glutathione. Retrotope is advancing RT001. RT001 is a deuterated synthetic homologue of ethyl linoleate, an essential omega-6 polyunsaturated fatty acid which is one of the major components of lipid membranes, particularly in mitochondria. Oxidation  damage might be reduced if the polyunsaturated fatty acids in the lipids were made more rigid and less susceptible to oxidation by the replacement of hydrogen atoms with the heavy hydrogen isotope deuterium. Modulation of frataxin controlled metabolic pathways
Dimethyl fumarate has been shown to increase frataxin levels in FRDA cells, mouse models, and humans. DMF showed an 85% increase in frataxin expression over 3 months in multiple sclerosis . Frataxin replacements or stabilizers
EPO mimetics are orally available peptide imitations of erythropoietin. They are small molecules erythropoietin receptor agonists designed to activate the tissue-protective erythropoietin receptor. Etravirine, an antiviral drug used to treat HIV, was found in a drug repositioning screening to increase frataxin levels in peripheral cells. Fratagene Therapeutics is developing a small molecule called RNF126 to inhibit an enzyme which degrades frataxin. Increase frataxin gene expression
Resveratrol might improve mitochondrial function. Nicotinamide (vitamin B3) was found effective in preclinical FRDA models and well tolerated. An RNA-based approach might unsilence the FXN gene and increase the expression of frataxin. Non-coding RNA (ncRNA) could be responsible for directing the localized epigenetic silencing of the FXN gene.
A rickettsiosis is a disease caused by intracellular bacteria. Cause
Rickettsioses can be divided into a spotted fever group (SPG) and typhus group (TG).In the past, rickettsioses were considered to be caused by species of Rickettsia. However, scrub typhus is still considered a rickettsiosis, even though the causative organism has been reclassified from Rickettsia tsutsugamushi to Orientia tsutsugamushi.Examples of rickettsioses include typhus, both endemic and epidemic, Rocky Mountain spotted fever, and Rickettsialpox. Organisms involved include Rickettsia parkeri.Many new causative organisms have been identified in the last few decades. Most are in the genus Rickettsia, but scrub typhus is in the genus Orientia. Diagnosis
No rapid laboratory tests are available to diagnose rickettsial diseases early in the course of illness, and serologic assays usually take 10–12 days to become positive. Research is indicating that swabs of eschars may be used for molecular detection of rickettsial infections. Treatment
Doxycycline has been used in the treatment of rickettsial infection. References
External links
 Media related to Rickettsioses at Wikimedia Commons