Positive effect of erythrocyte-delivered dexamethasone in ataxia-telangiectasia. Issue 3 (June 2015)

• Record Type: Journal Article
• Authors: Leuzzi, Vincenzo; Micheli, Roberto; D'Agnano, Daniela; Molinaro, Anna; Venturi, Tullia; Plebani, Alessandro; Soresina, Annarosa; Marini, Mirella; Ferremi Leali, Pierino; Quinti, Isabella; Pietrogrande, Maria C.; Finocchi, Andrea; Fazzi, Elisa; Chessa, Luciana; Magnani, Mauro
• Is Part Of: Neurology. Volume 2:Issue 3(2015)
• Publication Date: 2015-06
• Subjects: Neuroimmunology -- Periodicals; Neurology -- Periodicals; 616.8
• DOI: 10.1212/NXI.0000000000000098
• Languages: English
• ISSNs: 2332-7812

Abstract

Abstract : Objective: Ataxia-telangiectasia (AT) is a rare, devastating neurodegenerative disease presenting with early-onset ataxia, oculocutaneous telangiectasia, immunodeficiency, radiosensitivity, and proneness to cancer. In a previous phase 2 study, we showed that 6 monthly infusions of autologous erythrocytes loaded with dexamethasone (EryDex; EryDel, Urbino, Italy) were effective in improving neurologic impairment in young patients with AT. The present article reports the results of the extension of this study for an additional 24-month period. Methods: After the end of the first trial, 4 patients continued to be treated with monthly EryDex infusions for an additional 24 months, and their clinical outcome was compared with that of 7 age-matched patients who stopped the treatment after the first 6 infusions. The protocol included serial assessment of ataxia (by International Cooperative Ataxia Rating Scale) and adaptive behavior (by Vineland Adaptive Behavior Scales) and clinical and laboratory tests revealing treatment- and steroid-dependent adverse effects, if present. Results: Patients in the extended study experienced a continuous neurologic improvement with respect to their pretreatment status, whereas controls showed a progressive neurologic deterioration (according to the natural history of the disease) after the discontinuation of the treatment. The delivery system we adopted proved to be safe and well-tolerated, and none of the side effects usually associated with the chronic administration of corticosteroids were observed during the entire trial. Conclusions: These promising preliminary results call for a large-scale controlled study on protracted treatment of patients with AT with dexamethasone-loaded erythrocytes.