title: Intra-erythrocyte infusion of dexamethasone reduces neurological symptoms in ataxia teleangiectasia patients: results of a phase 2 trial.
abstract: BACKGROUND
  Ataxia Teleangiectasia [AT] is a rare neurodegenerative disease characterized by early onset ataxia, oculocutaneous teleangiectasias, immunodeficiency, recurrent infections, radiosensitivity and proneness to cancer. No therapies are available for this devastating disease. Recent observational studies in few patients showed beneficial effects of short term treatment with betamethasone. To avoid the characteristic side effects of long-term administration of steroids we developed a method for encapsulation of dexamethasone sodium phosphate (DSP) into autologous erythrocytes (EryDex) allowing slow release of dexamethasone for up to one month after dosing. Aims of the study were: the assessment of the effect of EryDex in improving neurological symptoms and adaptive behaviour of AT patients; the safety and tolerability of the therapy.
  
  
  METHODS
  Twenty two patients (F:M=1; mean age 11.2 ± 3.5) with a confirmed diagnosis of AT and a preserved or partially supported gait were enrolled for the study. The subjects underwent for six months a monthly infusion of EryDex. Ataxia was assessed by the International Cooperative Ataxia Rating Scale (ICARS) and the adaptive behavior by Vineland Adaptive Behavior Scales (VABS). Clinical evaluations were performed at baseline and 1, 3, and 6 months.
  
  
  RESULTS
  An improvement in ICARS (reduction of the score) was detected in the intention-to-treat (ITT) population (n=22; p=0.02) as well as in patients completing the study (per protocol PP) (n=18; p=0.01), with a mean reduction of 4 points (ITT) or 5.2 points (PP). When compared to baseline, a significant improvement were also found in VABS (increase of the score) (p<0.0001, ITT, RMANOVA), with statistically significant increases at 3 and 6 months (p<0.0001). A large inter-patient variability in the incorporation of DSP into erythrocytes was observed, with an evident positive effect of higher infusion dose on ICARS score decline. Moreover a more marked improvement was found in less neurologically impaired patients. Finally, a 19 month-extension study involving a subgroup of patients suggested that Erydex treatment can possibly delay the natural progression of the disease.EryDex was well tolerated; the most frequent side effects were common AT pathologies.
  
  
  CONCLUSIONS
  EryDex treatment led to a significant improvement in neurological symptoms, without association with the typical steroid side effects.
  
  
  BACKGROUND
  Current Controlled Trial 2010-022315-19SpA.
authors.forename: Luciana
authors.initials: L
authors.lastname: Chessa
authors.affiliation: Department of Pediatrics and Child Neurology and Psychiatry, Sapienza Università di Roma, via dei Sabelli 108, 00185 Roma, Italy. vincenzo.leuzzi@uniroma1.it.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Leuzzi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.forename: Annarosa
authors.initials: A
authors.lastname: Soresina
authors.forename: Roberto
authors.initials: R
authors.lastname: Micheli
authors.forename: Daniela
authors.initials: D
authors.lastname: D'Agnano
authors.forename: Tullia
authors.initials: T
authors.lastname: Venturi
authors.forename: Anna
authors.initials: A
authors.lastname: Molinaro
authors.forename: Elisa
authors.initials: E
authors.lastname: Fazzi
authors.forename: Mirella
authors.initials: M
authors.lastname: Marini
authors.forename: Pierino
authors.initials: P
authors.lastname: Ferremi Leali
authors.forename: Isabella
authors.initials: I
authors.lastname: Quinti
authors.forename: Filomena Monica
authors.initials: FM
authors.lastname: Cavaliere
authors.forename: Gabriella
authors.initials: G
authors.lastname: Girelli
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Pietrogrande
authors.forename: Andrea
authors.initials: A
authors.lastname: Finocchi
authors.forename: Stefano
authors.initials: S
authors.lastname: Tabolli
authors.forename: Damiano
authors.initials: D
authors.lastname: Abeni
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
mesh_terms: D000293:Adolescent; D001260:Ataxia Telangiectasia / Q000188:drug therapy*; D002648:Child; D003907:Dexamethasone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018450:Disease Progression; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male
chemical_list: C004180:dexamethasone 21-phosphate; D003907:Dexamethasone