Algorithm for the Early Diagnosis and Treatment of Patients with Cross Reactive Immunologic Material-Negative Classic Infantile Pompe Disease: A Step towards Improving the Efficacy of ERT

• DOI: 10.1371/journal.pone.0067052
• Publication Date: 2013-06-25T21:08:19Z
• Authors: Suhrad G. Banugaria; Sean N. Prater; Trusha T. Patel; Stephanie M. DeArmey; Christie Milleson; Kathryn B. Sheets; Deeksha S. Bali; Catherine W. Rehder; Julian A. J. Raiman; Raymond A. Wang; Francois Labarthe; Joel Charrow; Paul Harmatz; Pranesh Chakraborty; Amy S. Rosenberg; Priya S. Kishnani
• Keywords: Murine-Derived; Male; Time Factors; General Science & Technology; Science; 610; Immunoglobulins; Cross Reactions; Antibodies; Antibodies, Monoclonal, Murine-Derived; 03 medical and health sciences; Rare Diseases; 0302 clinical medicine; Clinical Research; 616; Monoclonal; Humans; Enzyme Replacement Therapy; Pediatric; Immunosuppression Therapy; Clinical Laboratory Techniques; Glycogen Storage Disease Type II; Prevention; Q; R; Infant, Newborn; Evaluation of treatments and therapeutic interventions; Infant; Newborn; 3. Good health; Early Diagnosis; Methotrexate; Treatment Outcome; 6.1 Pharmaceuticals; Medicine; Female; Safety; Rituximab; Immunosuppression; Algorithms; Research Article

Objective Although enzyme replacement therapy (ERT) is a highly effective therapy, CRIM-negative (CN) infantile Pompe disease (IPD) patients typically mount strong immune response which abrogates the efficacy of ERT, resulting in clinical decline and death. This study was designed to demonstrate that tolerance induction (ITI) prevents or diminishes development antibody titers, better outcome compared CN IPD treated with ERT monotherapy. Methods We evaluated safety, feasibility algorithm accurately identify minimize delays between CRIM status determination initiation an ITI regimen (combination rituximab, methotrexate IVIG) concurrent ERT. Clinical laboratory data including measures analysis for were analyzed Results Seven identified started on Median time from diagnosis commencement 0.5 months (range: 0.1–1.6 months). At baseline, all had significant cardiomyopathy but one required respiratory support. The safely tolerated seven cases. Four never seroconverted remained antibody-free. One patient died failure. Two another course regimen. In addition their improvement, titers observed these much lower than those seen monotherapy patients. Conclusions appears safe efficacious holds promise altering natural history by increasing efficacy. An such as this substantiates benefits accelerated management patients, thus, further supporting importance early identification treatment newborn screening IPD.