Targeting NLRP3 Inflammasome With Nrf2 Inducers in Central Nervous System Disorders

Tastan B, Arioz BI, Genc S.;Frontiers in Immunology. 2022 ;13:865772. DOI: 10.3389/fimmu.2022.865772. PMID: 35418995; PMCID: PMC8995746. 

 In this review, current knowledge on NLRP3 inflammasome activation and Nrf2 pathways is presented; the relationship between NLRP3 inflammasome signaling and Nrf2 pathway, as well as the pre/clinical use of Nrf2 activators against NLRP3 inflammasome activation in disorders of the central nervous system, are thoroughly described. Cumulative evidence points out therapeutic use of Nrf2 activators against NLRP3 inflammasome activation or diseases that NLRP3 inflammasome contributes to would be advantageous to prevent inflammatory conditions; however, the side effects of these molecules should be kept in mind before applying them to clinical practice.

Phase IA Study of AAVrh.10hFXN Gene Therapy for the Cardiomyopathy of Friedreich's Ataxia

ClinicalTrials.gov Identifier: NCT05302271; Recruitment Status : Recruiting; First Posted : March 31, 2022 Sponsor: Weill Medical College of Cornell University 

The purpose of this study is to test the safety and preliminary efficacy of AAVrh.10hFXN to treat the cardiomyopathy associated with Friedreich's ataxia (FA). AAVrh.10hFXN is a serotype rh.10 adeno-associated virus gene transfer vector coding for Frataxin (FXN). The drug is administered intravenously. This is a phase 1, open label, dose escalation study with a total of 10 participants. Drug: Prednisone, all participants will remain immunosuppression therapy with prednisone for a total of 14 weeks.

Friedreich’s ataxia-associated childhood hypertrophic cardiomyopathy: a national cohort study

Norrish G, Rance T, Montanes E, et al.; Archives of Disease in Childhood 2022;107:450-455. 

This is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly.