title: ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density.
abstract: Small nerve fiber loss and damage (SNFLD) is a frequent complication of sarcoidosis that is associated with autonomic dysfunction and sensory abnormalities, including pain syndromes that severely degrade the quality of life. SNFLD is hypothesized to arise from the effects of immune dysregulation, an essential feature of sarcoidosis, on the peripheral and central nervous systems. Current therapy of sarcoidosis-associated SNFLD consists primarily of immune suppression and symptomatic treatment; however, this treatment is typically unsatisfactory. ARA 290 is a small peptide engineered to activate the innate repair receptor that antagonizes inflammatory processes and stimulates tissue repair. Here we show in a blinded, placebo-controlled trial that 28 d of daily subcutaneous administration of ARA 290 in a group of patients with documented SNFLD significantly improves neuropathic symptoms. In addition to improved patient-reported symptom-based outcomes, ARA 290 administration was also associated with a significant increase in corneal small nerve fiber density, changes in cutaneous temperature sensitivity, and an increased exercise capacity as assessed by the 6-minute walk test. On the basis of these results and of prior studies, ARA 290 is a potential disease-modifying agent for treatment of sarcoidosis-associated SNFLD.
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Albert
authors.initials: A
authors.lastname: Dahan
authors.affiliation: Araim Pharmaceuticals, Ossining, New York, United States of America.
authors.forename: Ann
authors.initials: A
authors.lastname: Dunne
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Swartjes
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Paolo L
authors.initials: PL
authors.lastname: Proto
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Lara
authors.initials: L
authors.lastname: Heij
authors.affiliation: Department of Neurology, St. Antonius Hospital, Nieuwegein, the Netherlands.
authors.forename: Oscar
authors.initials: O
authors.lastname: Vogels
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Monique
authors.initials: M
authors.lastname: van Velzen
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Elise
authors.initials: E
authors.lastname: Sarton
authors.affiliation: Department of Anesthesiology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Niesters
authors.affiliation: Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martijn R
authors.initials: MR
authors.lastname: Tannemaat
authors.affiliation: Araim Pharmaceuticals, Ossining, New York, United States of America Department of Internal Medicine, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Anthony
authors.initials: A
authors.lastname: Cerami
authors.affiliation: Araim Pharmaceuticals, Ossining, New York, United States of America.
authors.forename: Michael
authors.initials: M
authors.lastname: Brines
mesh_terms: D003315:Cornea / Q000187:drug effects* / Q000294:innervation; D004334:Drug Administration Schedule; D004916:Erythromelalgia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D005080:Exercise Test; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009412:Nerve Fibers / Q000187:drug effects / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage / Q000627:therapeutic use*; D012507:Sarcoidosis / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology
chemical_list: D009842:Oligopeptides; C576178:cibinetide