Various preclinical studies have shown the feasibility and efficacy of utilizing NPs for gene delivery in PD models
& Chen, T
In light of these preclinical results, standard and specialized neurologic and audiologic safety assessments and adjudication of events were conducted across the ALLEGRO program.25 Clinical data from the integrated safety analysis, including adjudicated events deemed possible neurologic or audiologic events of interest, showed no evidence of neurotoxicity with ritlecitinib treatment.25 Most AEs associated with neurologic events of interest such as dysesthesia, hyperesthesia, hypoesthesia, and paresthesia were mild in severity, considered by investigators to be unrelated to treatment, and resolved spontaneously.25 In a placebo-controlled phase 2a clinical safety study specifically evaluating potential neurologic/neuroaudiologic effects of ritlecitinib in adults with AA using BAEP assessments and intraepidermal axon histology, no notable effects were observed on nerve fiber counts, intraepidermal axon inflammation, or integrity of the human brainstem auditory pathway as assessed by BAEP.25 These data support that the dog finding of axonal dystrophy is not clinically relevant in humans.25 Laboratory assessments Ritlecitinib was associated with early, dose-dependent decreases in lymphocyte counts
Researchers designing combination protocols typically run controls with each compound in isolation alongside the combination arms to distinguish additive from synergistic effects and to identify which compound is driving each observed outcome
Li J, Liu F, Wang H et al (2010) Systematic mapping and functional analysis of a family of human epididymal secretory sperm-located proteins
Recent evidence has suggested that GPx1 and c-Src tyrosine kinases participate in the phosphorylation of IB which, in response to hypoxia, leads to the activation of NF-B elevated in hydrogen peroxide-treated embryonic fibroblasts [50]
