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.
|Mauer, Michael; Glynn, Emily; Svarstad, Einar et al. (2014) Mosaicism of podocyte involvement is related to podocyte injury in females with Fabry disease. PLoS One 9:e112188|
|Rumsey, Robin K; Rudser, Kyle; Delaney, Kathleen et al. (2014) Acquired autistic behaviors in children with mucopolysaccharidosis type IIIA. J Pediatr 164:1147-1151.e1|
|Schiffmann, Raphael; Forni, Sabrina; Swift, Caren et al. (2014) Risk of death in heart disease is associated with elevated urinary globotriaosylceramide. J Am Heart Assoc 3:e000394|
|Polgreen, Lynda E; Thomas, William; Fung, Ellen et al. (2014) Low bone mineral content and challenges in interpretation of dual-energy X-ray absorptiometry in children with mucopolysaccharidosis types I, II, and VI. J Clin Densitom 17:200-6|
|Polgreen, Lynda E; Thomas, William; Orchard, Paul J et al. (2014) Effect of recombinant human growth hormone on changes in height, bone mineral density, and body composition over 1-2 years in children with Hurler or Hunter syndrome. Mol Genet Metab 111:101-6|
|Stevenson, David A; Rudser, Kyle; Kunin-Batson, Alicia et al. (2014) Biomarkers of bone remodeling in children with mucopolysaccharidosis types I, II, and VI. J Pediatr Rehabil Med 7:159-65|
|Prater, Sean N; Banugaria, Suhrad G; Morgan, Claire et al. (2014) Letter to the Editors: Concerning "CRIM-negative Pompe disease patients with satisfactory clinical outcomes on enzyme replacement therapy" by Al Khallaf et al. J Inherit Metab Dis 37:141-3|
|Schiffmann, Raphael; Mayfield, Joan; Swift, Caren et al. (2014) Quantitative neuroimaging in mucolipidosis type IV. Mol Genet Metab 111:147-51|
|Wang, Raymond Y; Braunlin, Elizabeth A; Rudser, Kyle D et al. (2014) Carotid intima-media thickness is increased in patients with treated mucopolysaccharidosis types I and II, and correlates with arterial stiffness. Mol Genet Metab 111:128-32|
|Ahmed, Alia; Whitley, Chester B; Cooksley, Renee et al. (2014) Neurocognitive and neuropsychiatric phenotypes associated with the mutation L238Q of the *-L-iduronidase gene in Hurler-Scheie syndrome. Mol Genet Metab 111:123-7|
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