Chemistry:Leriglitazone
Leriglitazone is a PPAR-gamma agonist and metabolite of the glitazone pioglitazone.[1] It is an active metabolite of pioglitazone, and a selective peroxisome proliferator-activated receptor gamma (PPARγ) agonist that crosses the blood-brain barrier (BBB).[1] Lerigltazone has been reported to have an antioxidant and neuroprotective activity in the central nervous system by modulating critical pathways involved in cerebral adrenoleukodystrophy progression and consequently decreasing neuroinflammation, enhancing BBB integrity, promoting myelination and improving mitochondrial function.[1]
The most common side effects in children were weight increase, eyelid edema, leukopenia, and neutropenia.[1]
History
The benefits of leriglitazone were shown in an open-label study which measured the effects of leriglitazoneon disease progression prior to hematopoietic stem cell transplantation (HSCT), in boys aged 2 to 12 years old with cerebral adrenoleukodystrophy.[1]
Society and culture
Legal status
In January 2024, the European Medicines Agency (EMA) recommended the refusal of the marketing authorization for leriglitazone (Nezglyal) requested by Minoryx Therapeutics S.L.[1] In May 2024, the EMA confirmed its recommendation to refuse marketing authorization for leriglitazone.[1]
In July 2026, the Committee for Medicinal Products for Human Use of the EMA adopted a positive opinion recommending the granting of a marketing authorization under exceptional circumstances for the medicinal product Nezglyal, intended for the treatment of cerebral adrenoleukodystrophy.[1] The applicant for this medicinal product is Minoryx Therapeutics.[1][2][3]
References
- ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Nezglyal EPAR". 25 January 2024. https://www.ema.europa.eu/en/medicines/human/EPAR/nezglyal. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- ↑ "Nezglyal (leriglitazone) receives a positive CHMP opinion for the treatment of cerebral Adrenoleukodystrophy (cALD), a rare neurodegenerative disease". Minoryx official website (Press release). 24 July 2026. Retrieved 10 September 2026.
- ↑ "Minoryx and Neuraxpharm complete enrolment in leriglitazone pivotal Phase 3 trial (CALYX) in adult patients with cerebral Adrenoleukodystrophy (cALD)". Minoryx (Press release). 9 September 2026. Retrieved 10 September 2026.
Further reading
- Musokhranova, Uliana; Grau, Cristina; Vergara, Cristina; Rodríguez-Pascau, Laura; Xiol, Clara; Castells, Alba A.; Alcántara, Soledad; Rodríguez-Pombo, Pilar et al. (26 October 2023). "Mitochondrial modulation with leriglitazone as a potential treatment for Rett syndrome". Journal of Translational Medicine 21 (1): 756. doi:10.1186/s12967-023-04622-5. ISSN 1479-5876. PMID 37884937.
- Pandolfo, Massimo; Reetz, Kathrin; Darling, Alejandra; Rodriguez de Rivera, Francisco Javier; Henry, Pierre-Gilles; Joers, James; Lenglet, Christophe; Adanyeguh, Isaac et al. (December 2022). "Efficacy and Safety of Leriglitazone in Patients With Friedreich Ataxia: A Phase 2 Double-Blind, Randomized Controlled Trial (FRAMES)". Neurology: Genetics 8 (6). doi:10.1212/NXG.0000000000200034. PMID 36524101.
- Pizcueta, Pilar; Vergara, Cristina; Emanuele, Marco; Vilalta, Anna; Rodríguez-Pascau, Laura; Martinell, Marc (6 February 2023). "Development of PPARγ Agonists for the Treatment of Neuroinflammatory and Neurodegenerative Diseases: Leriglitazone as a Promising Candidate". International Journal of Molecular Sciences 24 (4): 3201. doi:10.3390/ijms24043201. ISSN 1422-0067. PMID 36834611.
- Rodríguez-Pascau, Laura; Vilalta, Anna; Cerrada, Marc; Traver, Estefania; Forss-Petter, Sonja; Weinhofer, Isabelle; Bauer, Jan; Kemp, Stephan et al. (2 June 2021). "The brain penetrant PPARγ agonist leriglitazone restores multiple altered pathways in models of X-linked adrenoleukodystrophy". Science Translational Medicine 13 (596). doi:10.1126/scitranslmed.abc0555. PMID 34078742. https://zenodo.org/record/6419212.
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