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| Formula | C27H45NO |
| Molar mass | 399.65 g·mol−1 |
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Olesoxime (TRO19622) is an experimental drug formerly under development by the now-defunct French company Trophos as a treatment for a range of neuromuscular disorders. It has a cholesterol-like structure and belongs to the cholesterol-oxime family of mitochondrial pore modulators.
Research
In preclinical studies, the compound displayed neuroprotective properties by promoting the function and survival of neurons and other cell types under disease-relevant stress conditions. It did so through interactions with two components of the mitochondrial permeability transition pore (mPTP), VDAC and TSPO. In preclinical studies on Huntington's disease, the disease-attenuating effects of olesoxime were attributed to modulating the activity of calcium-dependent proteases called calpains.
A 2009–2011 phase 3 clinical trial in amyotrophic lateral sclerosis did not demonstrate an increase in survival. A 2011–2013 trial in spinal muscular atrophy (SMA) indicated that the compound may prevent deterioration of muscle function. In 2015, the entire olesoxime programme was purchased by Hoffmann-La Roche for €120 million with a view to developing a treatment for SMA. However, in June 2018, faced with technical and regulatory challenges and competition from a potentially more effective drug nusinersen, Roche halted further development of olesoxime.
Further reading
- Rovini A, Carré M, Bordet T, Pruss RM, Braguer D (September 2010). "Olesoxime prevents microtubule-targeting drug neurotoxicity: selective preservation of EB comets in differentiated neuronal cells". Biochemical Pharmacology. 80 (6): 884–94. doi:10.1016/j.bcp.2010.04.018. PMID 20417191.
- Xiao WH, Zheng FY, Bennett GJ, Bordet T, Pruss RM (December 2009). "Olesoxime (cholest-4-en-3-one, oxime): analgesic and neuroprotective effects in a rat model of painful peripheral neuropathy produced by the chemotherapeutic agent, paclitaxel". Pain. 147 (1–3): 202–9. doi:10.1016/j.pain.2009.09.006. PMC 2787910. PMID 19833436.
- Bordet T, Buisson B, Michaud M, Abitbol JL, Marchand F, Grist J, Andriambeloson E, Malcangio M, Pruss RM (August 2008). "Specific antinociceptive activity of cholest-4-en-3-one, oxime (TRO19622) in experimental models of painful diabetic and chemotherapy-induced neuropathy". The Journal of Pharmacology and Experimental Therapeutics. 326 (2): 623–32. doi:10.1124/jpet.108.139410. PMID 18492948. S2CID 33726393.
External links
- cholest-4-en-3-one, oxime at the U.S. National Library of Medicine Medical Subject Headings (MeSH)'