ARA 290 improves symptoms in patients with sarcoidosis-associated small nerve fiber loss and increases corneal nerve fiber density

Mol Med. 2013 Nov 8;19(1):334-45. doi: 10.2119/molmed.2013.00122.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cornea / drug effects*
  • Cornea / innervation
  • Drug Administration Schedule
  • Erythromelalgia / drug therapy*
  • Erythromelalgia / etiology
  • Erythromelalgia / pathology
  • Exercise Test
  • Female
  • Humans
  • Injections, Subcutaneous
  • Male
  • Microscopy, Confocal
  • Middle Aged
  • Nerve Fibers / drug effects
  • Nerve Fibers / pathology
  • Oligopeptides / administration & dosage
  • Oligopeptides / therapeutic use*
  • Sarcoidosis / complications*
  • Sarcoidosis / drug therapy*
  • Sarcoidosis / pathology

Substances

  • Oligopeptides
  • cibinetide