The availability of enzyme replacement therapy (ERT) with algucosidase alfa (rhGAA, Myozyme, Lumizyme) has been commercially available since 2006 and, in general, has improved the natural history for patients with Infantile Pompe Disease (IPD). Cross Reactive Immunologic Material (CRIM) status is a well-appreciated factor influencing clinical outcomes, as patients who are characterized as CRIM-negative (CN) with no residual GAA enzyme activity are at risk to develop a strong immune response against rhGAA resulting in clinical decline and ultimately death despite continued ERT. Additionally, a subset of CRIM-positive (CP) patients also develope high sustained antibody titers (HSAT). We have developed and demonstrated the success of immune modulation prophylactically in CN patients prior to starting ERT, as well as for CN and CP patients in the entrenched setting after the development of HSAT. With such advances in treatment IPD patients are living longer, transforming the clinical course of Pompe disease as we know it. Further investigation is needed to characterize the emerging natural history of IPD survivors and assess the efficacy of immune tolerance induction (ITI) and suppression algorithms. With supplemental support from Genzyme Corporation and the Alice &YT Chen Pediatrics Genetics &Genomics Research Center, continuation of this observational study [LDN6709;Duke IRB Pro00001562] aims to 1) explore clinical response to treatment in CP and CN IPD patients receiving ERT with and without immune suppression regimens through prospective and retrospective data collection;2) continue to correlate GAA genotype with CRIM status in association with immune responses;and 3) assess efficacy of immune modulation prophylactically in CN IPD, suppression of HSAT in the entrenched setting, as well as assess prophylactic ITI for CP IPD. Continued long-term clinical data collection will help us to gain a better understanding of natural history and treatment outcomes in IPD, which is expected to guide the use or development of new therapeutic interventions for the next generation of IPD patientsthe importance of which is underscored by the advent of newborn screening for IPD.
ERT is a highly effective treatment for patients with IPD;however, some patients develop a strong immune response resulting in significant clinical decline or death despite continued ERT. This research aims to assess various treatment approaches to improve the clinical outcomes and quality of life of not only IPD patients, but also patients with other lysosomal storage disorders similarly treated with therapeutic proteins.
|Ou, Li; Przybilla, Michael J; Whitley, Chester B (2018) Metabolomics profiling reveals profound metabolic impairments in mice and patients with Sandhoff disease. Mol Genet Metab :|
|McIntosh, Paul T; Hobson-Webb, Lisa D; Kazi, Zoheb B et al. (2018) Neuroimaging findings in infantile Pompe patients treated with enzyme replacement therapy. Mol Genet Metab 123:85-91|
|Nestrasil, Igor; Ahmed, Alia; Utz, Josephine M et al. (2018) Distinct progression patterns of brain disease in infantile and juvenile gangliosidoses: Volumetric quantitative MRI study. Mol Genet Metab 123:97-104|
|Ou, Li; Przybilla, Michael J; Koniar, Brenda et al. (2018) RTB lectin-mediated delivery of lysosomal ?-l-iduronidase mitigates disease manifestations systemically including the central nervous system. Mol Genet Metab 123:105-111|
|Desai, Ankit K; Walters, Crista K; Cope, Heidi L et al. (2018) Enzyme replacement therapy with alglucosidase alfa in Pompe disease: Clinical experience with rate escalation. Mol Genet Metab 123:92-96|
|Sindelar, Miriam; Dyke, Jonathan P; Deeb, Ruba S et al. (2018) Untargeted Metabolite Profiling of Cerebrospinal Fluid Uncovers Biomarkers for Severity of Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2, Batten Disease). Sci Rep 8:15229|
|Shapiro, Elsa G; Whitley, Chester B; Eisengart, Julie B (2018) Beneath the floor: re-analysis of neurodevelopmental outcomes in untreated Hurler syndrome. Orphanet J Rare Dis 13:76|
|Ou, L; Przybilla, M J; Whitley, C B (2018) SAAMP 2.0: An algorithm to predict genotype-phenotype correlation of lysosomal storage diseases. Clin Genet 93:1008-1014|
|Eisengart, Julie B; Rudser, Kyle D; Xue, Yong et al. (2018) Long-term outcomes of systemic therapies for Hurler syndrome: an international multicenter comparison. Genet Med 20:1423-1429|
|Kazi, Zoheb B; Desai, Ankit K; Troxler, R Bradley et al. (2018) An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease. Genet Med :|
Showing the most recent 10 out of 118 publications