title: Therapy with eculizumab for patients with CD59 p.Cys89Tyr mutation.
abstract: OBJECTIVE
  The objective of this work was to report on the outcome of eculizumab treatment in pediatric patients with recurrent acute predominantly motor, demyelinating neuropathy with conduction block, and chronic hemolysis attributed to p.Cys89Tyr mutation in the CD59 gene.
  
  
  METHODS
  Four patients were recruited from our new registry of patients with homozygosity for the p.Cys89Tyr mutation on CD59. Participants received repeated intravenous eculizumab. In this 24-month open-label phase IIa study, we aimed to determine whether eculizumab reduces chronic hemolysis, and cumulative doses of steroids and intravenous immunoglobulin (IVIG), and ameliorates neurological deficits, compared to pretreatment status. Treatment response was evaluated every 2 to 4 weeks over 104 weeks and included examination with gross motor scoring by American Spinal Injury Association Impairment Scale and Inflammatory Neuropathy Cause and Treatment disability score, laboratory examination, well-being [12-item Short Form Health Survey; SF-12]). Neurological relapses and cumulative dose of IVIGs and/or corticosteroids before and after treatment were documented. Red blood cells (RBCs) and neutrophils were stained to evaluate C5b-9 deposition. ClinicalTrials.gov: NCT01579838.
  
  
  RESULTS
  Dramatic and significant neurological amelioration in the upper limbs and trunk with more-modest amelioration in the lower limbs was observed in all patients. Corticosteroid and IVIG treatment was completely stopped. No patient relapsed during treatment despite infections, and there were no hospital admissions. Decreased C3bi and C5b-9 deposition on RBCs and neutrophils was documented (p < 0.0001). The SF-12 health questionnaires indicated significant improvement (p < 0.003).
  
  
  CONCLUSIONS
  Eculizumab was safely administered to these patients. Marked clinical improvement suggests that eculizumab may be a life-saving treatment for patients with acute predominantly motor, demyelinating neuropathy with conduction block, and secondary axonal damage attributed to primary p.Cys89Tyr mutation in the CD59 gene. Ann Neurol 2016;80:708-717.
authors: Rheumatology Research Center and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Dror
authors: D
authors: Mevorach
authors: Rheumatology Research Center and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Inna
authors: I
authors: Reiner
authors: Rheumatology Research Center and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Amir
authors: A
authors: Grau
authors: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Uri
authors: U
authors: Ilan
authors: Department of Pediatrics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Yackov
authors: Y
authors: Berkun
authors: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Asaf
authors: A
authors: Ta-Shma
authors: Monique and Jacques Roboh Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Orly
authors: O
authors: Elpeleg
authors: Neuropediatric Unit, Soroka Medical Center, Beer Sheba, Israel.
authors: Zamir
authors: Z
authors: Shorer
authors: Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Simon
authors: S
authors: Edvardson
authors: Rheumatology Research Center and Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
authors: Adi
authors: A
authors: Tabib
mesh_terms: D000743:Anemia, Hemolytic / Q000150:complications*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000494:pharmacology*; D018957:CD59 Antigens / Q000235:genetics*; D002675:Child, Preschool; D005260:Female; D006456:Hemoglobinuria / Q000150:complications*; D006461:Hemolysis / Q000187:drug effects*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D011129:Polyradiculoneuropathy / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D012042:Registries; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018957:CD59 Antigens; C051590:CD59 protein, human; C481642:eculizumab