title: NP001 regulation of macrophage activation markers in ALS: a phase I clinical and biomarker study.
abstract: This is a phase I, placebo-controlled, single ascending dose safety and tolerability study of NP001 in patients with ALS. NP001 is a novel regulator of inflammatory macrophages and monocytes. As ALS progression is thought to be related to neuroinflammation, an additional objective of the study was to assess the effects of NP001 administration on monocyte activation markers. Thirty-two ALS patients were enrolled and received either placebo (eight) or one of four (six at each dose) ascending single i.v. doses (0.2, 0.8, 1.6 and 3.2 mg/kg NP001). Patients were monitored for safety, and blood monocyte immune activation markers CD16 and HLA-DR were assessed pre- and 24 h post-dosing. Changes from baseline were calculated. Results showed that NP001 was generally safe and well tolerated. Importantly, a single dose of NP001 caused a dose-dependent reduction in expression of monocyte CD16, a marker of monocyte activation/inflammation. Additionally, monocyte HLA-DR expression was also decreased in those patients with elevated values at baseline. In conclusion, these data indicate that NP001 has an acute effect on inflammatory monocytes in ALS patient blood. The potential for modulation of inflammation in the context of ALS disease progression will require further study with long-term follow-up.
authors.affiliation: California Pacific Medical Center , San Francisco.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Miller
authors.forename: Rongzhen
authors.initials: R
authors.lastname: Zhang
authors.forename: Gilbert
authors.initials: G
authors.lastname: Block
authors.forename: Jonathan
authors.initials: J
authors.lastname: Katz
authors.forename: Richard
authors.initials: R
authors.lastname: Barohn
authors.forename: Edward
authors.initials: E
authors.lastname: Kasarskis
authors.forename: Dallas
authors.initials: D
authors.lastname: Forshew
authors.forename: Vidhya
authors.initials: V
authors.lastname: Gopalakrishnan
authors.forename: Michael S
authors.initials: MS
authors.lastname: McGrath
mesh_terms: D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000188:drug therapy*; D000704:Analysis of Variance; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D002712:Chlorides / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D017452:Receptors, IgG / Q000378:metabolism; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D002712:Chlorides; D006684:HLA-DR Antigens; D017452:Receptors, IgG; C001599:chlorite
keywords: ALS; NP001; inflammation; macrophage; monocyte