Olesoxime

Olesoxime (TRO19622) is the lead compound of Trophos' proprietary cholesterol-oxime compound family of mitochondrial pore modulators. ^[1]

It is a molecule that has a cholesterol-like structure and displays strong neuroprotective properties. TRO19622 is as effective as a cocktail of three neurotrophic factors in keeping motor neurons alive in culture.^{[citation needed]}

Preclinical studies have demonstrated that the compound promotes the function and survival of neurons and other cell types under disease-relevant stress conditions through interactions with the mitochondrial permeability transition pore (mPTP).^[2]

Olesoxime has successfully completed phase I studies in healthy volunteers and phase Ib studies in Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy patients. These clinical trials showed that the product is well tolerated and has an excellent safety profile. They also showed that once-a-day oral dosing achieves the predicted exposure levels, required for efficacy, based on preclinical models.^{[3] [4]}

Drug interaction studies with riluzole, the only registered treatment for ALS, showed no interaction of TRO19622 on riluzole pharmacokinetics.

Olesoxime (TRO19622) is currently being developed for the treatment of two motor neuron diseases: Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA).

References

1. ^ http://www.ukmi.nhs.uk/applications/ndo/record_view_open.asp?newDrugID=5002
2. ^ Bordet, Thierry; Buisson, Bruno; Michaud, Magali; Drouot, Cyrille; Galéa, Pascale; Delaage, Pierre; Akentieva, Natalia P.; Evers, Alex S. et al. (2007). "Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis". The Journal of pharmacology and experimental therapeutics 322 (2): 709–20. doi:10.1124/jpet.107.123000. PMID 17496168. 
3. ^ "Effect of TRO19622 in the Treatment of Patients With Chemotherapy Induced Peripheral Neuropathy". ClinicalTrialsFeeds.org. 05 February 2010. http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00876538. Retrieved 3 October 2010. 
4. ^ "Safety and Efficacy of TRO19622 as add-on Therapy to Riluzole Versus Placebo in Treatment of Patients Suffering From Amyotrophic Lateral Sclerosis (ALS)". ClinicalTrialsFeeds.org. May 2010. http://clinicaltrialsfeeds.org/clinical-trials/show/NCT00868166. Retrieved 3 October 2010. 

Further reading

• Rovini, Amandine; Carré, Manon; Bordet, Thierry; Pruss, Rebecca M.; Braguer, Diane (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, Wen Hua; Zheng, Felix Y.; Bennett, Gary J.; Bordet, Thierry; Pruss, Rebecca M. (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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2787910. 
• Bordet, Thierry; Buisson, Bruno; Michaud, Magali; Abitbol, Jean-Louis; Marchand, Fabien; Grist, John; Andriambeloson, Emile; Malcangio, Marzia et al. (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. 
• Bordet, Thierry; Buisson, Bruno; Michaud, Magali; Drouot, Cyrille; Galéa, Pascale; Delaage, Pierre; Akentieva, Natalia P.; Evers, Alex S. et al. (2007). "Identification and characterization of cholest-4-en-3-one, oxime (TRO19622), a novel drug candidate for amyotrophic lateral sclerosis". The Journal of pharmacology and experimental therapeutics 322 (2): 709–20. doi:10.1124/jpet.107.123000. PMID 17496168.