Pompe disease (Glycogen storage disease type II;MIM 232300) is a classical lysosomal storage disorder that causes death in the first year of life for patients with the infantile form due to a progressive cardiomyopathy leading to cardiorespiratory failure. Myozyme (alglucosidase alpha, recombinant human acid alpha-glucosidase/GAA, rhGAA) was approved in April 2006 as a treatment for Pompe Disease. The availability of ERT with Myozyme has improved the outcome of most patients with Pompe disease;however, a subset of infantile Pompe patients responds poorly to ERT, subsequently dying from cardiorespiratory failure. Poorly-responding Pompe disease patients generally lack residual GAA expression and these patients are cross-reacting immune material-negative (CRIM-negative).
The Aims of this proposal would evaluate these rare CRIM-negative Pompe disease patients on ERT +/- immune suppression, by enrolling them in a prospective/retrospective natural history study through the Lysosomal Disease Network. Subjects would be enrolled from the Network and data collected regarding a number of clinical endpoints to determine the natural history of this disorder. Enrollment will include patients for whom a poor clinical response to current therapy is predicted. Patients studied will be all infantile crossreacting immune material (CRIM)-negative Pompe disease patients on a clinical protocol starting enzyme replacement therapy (ERT) with or without immune suppression. They will be compared to data obtained from infantile CRIM-positive Pompe disease patients started on ERT at similar ages and also enrolled in the protocol monitoring history and outcome of the disease on ERT.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54NS065768-05
Application #
8545229
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$71,904
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Type
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Schneider, Joseph; Burmeister, Lynn A; Rudser, Kyle et al. (2016) Hypothyroidism in late-onset Pompe disease. Mol Genet Metab Rep 8:24-7
Polgreen, Lynda E; Vehe, Richard K; Rudser, Kyle et al. (2016) Elevated TNF-α is associated with pain and physical disability in mucopolysaccharidosis types I, II, and VI. Mol Genet Metab 117:427-30
Shapiro, Elsa G; Rudser, Kyle; Ahmed, Alia et al. (2016) A longitudinal study of emotional adjustment, quality of life and adaptive function in attenuated MPS II. Mol Genet Metab Rep 7:32-9
Dyke, J P; Sondhi, D; Voss, H U et al. (2016) Brain Region-Specific Degeneration with Disease Progression in Late Infantile Neuronal Ceroid Lipofuscinosis (CLN2 Disease). AJNR Am J Neuroradiol 37:1160-9
Najafian, Behzad; Tøndel, Camilla; Svarstad, Einar et al. (2016) One Year of Enzyme Replacement Therapy Reduces Globotriaosylceramide Inclusions in Podocytes in Male Adult Patients with Fabry Disease. PLoS One 11:e0152812
Shapiro, E; King, K; Ahmed, A et al. (2016) The Neurobehavioral Phenotype in Mucopolysaccharidosis Type IIIB: an Exploratory Study. Mol Genet Metab Rep 6:41-47
Rappaport, Jeff; Manthe, Rachel L; Solomon, Melani et al. (2016) A Comparative Study on the Alterations of Endocytic Pathways in Multiple Lysosomal Storage Disorders. Mol Pharm 13:357-68
Ahmed, Alia; Shapiro, Elsa; Rudser, Kyle et al. (2016) Association of somatic burden of disease with age and neuropsychological measures in attenuated mucopolysaccharidosis types I, II and VI. Mol Genet Metab Rep 7:27-31
Karimian, Zahra; Whitley, Chester B; Rudser, Kyle D et al. (2016) Delayed Infusion Reactions to Enzyme Replacement Therapies. JIMD Rep :
Kazi, Zoheb B; Prater, Sean N; Kobori, Joyce A et al. (2016) Durable and sustained immune tolerance to ERT in Pompe disease with entrenched immune responses. JCI Insight 1:

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