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Project Details
Description
The mucopolysaccharidoses are monogenic, heritable disorders of lysosomal malfunction that cause
progressive multi-system organ damage. Early on, it was thought that the physical manifestations of MPS
commenced in childhood, but we now know that glycosaminoglycan deposition begins in utero and that
treatment beginning early in life, even infancy, does not ameliorate the burden of disease. Importantly, while
the primary effects of disease vary by genetic subtype—for example MPS I, II, and III come with a significant
cognitive impact, while MPS IV and VI, have central nervous system involvement that does not include
cognition—all of the MPS disorders, regardless of central nervous system burden, comprise significant skeletal
and organ deficits that results in lifelong disability; and that this disability exists regardless of treatment.
Current therapies have shown some effect in ameliorating the devastating brain disease, but have had little
somatic effect—especially as it relates to skeletal (bone) and cardiac (valve) involvement. As treatment
options for the MPS conditions continue to grow, and expand to include gene therapy, a systematic, thorough
categorization of disease effect across the lifetime individuals with MPS is more relevant than ever. Adding to
the need for early, longitudinal, descriptive data is the advent of newborn screening for MPS I to the panels in
several states. Those identified via a newborn screening present a unique opportunity to collect data from
individuals with MPS I beginning at birth. This data, in conjunction with that collected by our research team
over the last 10 years, provides the richest, most complete dataset available against which to measure new
therapy. Adding to the dataset in the ways described here, will lead to specific recommendations on how to
proceed therapeutically, after a diagnosis (via newborn screening or otherwise) for any MPS condition. The
Lysosomal Disease Network structure allows us to incorporate data from Centers of Excellence geographically
dispersed across the US and Canada to collect cross-tabulated data from the widest possible patient
population that: 1. Quantifies abnormalities and rates of progression in neurodevelopment by disease subtype,
2. Characterizes social, emotional, and behavioral profiles; correlated with treatment by disease subtype, 3.
Determines abnormalities in brain morphometry and white matter microstructure to define developmental
pathways by disease subtype, 4. Quantifies the burden of physical disability across organ systems and how
those disabilities impact development and psychosocial function, 5. Assess the full impact of MPS on skeletal
and cardiac systems across treatment modalities, and 6. Identify the incidence pattern of disease expression of
infants with Hurler syndrome identified by newborn screening, and how current stem cell transplant leads to
disease-related morbidity and mortality. Every aim presented will be evaluated in context with each other to
provide detailed, multi-dimensional data designed to define systematic burden as a measure for future therapy.
Status | Finished |
---|---|
Effective start/end date | 8/1/19 → 7/31/22 |
Funding
- National Institute of Neurological Disorders and Stroke: $449,649.00
- National Institute of Neurological Disorders and Stroke: $434,230.00
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Projects
- 1 Active
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Lysosomal Disease Network
Whitley, C. B., Ballon, D. J., Bjoraker, K. J., Cathey, S. S., Chen, A. H., Cloyd, J. C., Crystal, R. G., Grabowski, G. A., Kishnani, P. S., Kishnani, P. S., Langan, T. J., Levy, P., Mauer, M. S., Mink, J. W., Najafian, B., Patterson, M. C., Polgreen, L. E., Schiffmann, R. & Shapiro, E. G.
National Institute of Neurological Disorders and Stroke
9/30/09 → 7/31/24
Project: Research project