An observational study in Mucopolysaccharidosis Type I, sponsored by University of Minnesota. Completed at 1 site in United States. Open to participants aged 6 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2019-11-01.
Sponsored by University of Minnesota · Observational
Neuroinflammation and oxidative stress have been shown to be present in persons with mucopolysaccharidosis type I (MPS I), but their effect on disease severity and disease progression is unknown. The investigator intends to employ brain magnetic resonance spectroscopy (MRS), a non-invasive technique, along with analysis of neuroinflammation and oxidative stress biomarkers in the blood, to measure and determine the level of oxidative stress and neuroinflammation, and their impact on clinical variability in MPS I patients.
Persons with MPS I have a wide range of clinical manifestations including central nervous system (CNS) impairment. The role of neuroinflammation and oxidative stress is one avenue of investigation which may clarify the broad neurological impairment in MPS I. Finding biomarkers that accurately describe the underlying and ongoing brain pathology is a key not only to understanding the disease, but also to understanding the possibility of new therapeutic approaches for MPS I patients.
The investigator will compare patients with Hurler syndrome, and Hurler-Scheie or Scheie syndrome, with healthy controls. There will be 10 participants in each group, resulting in a total of 30 participants. Within the Hurler-Scheie or Scheie syndrome group, the investigator will examine the association of clinical severity with the proposed measures. These findings might help determine whether hematopoietic cell transplantation (HCT), which is the treatment for Hurler syndrome patients, results in decreased oxidative stress and neuroinflammation as compared to Hurler-Scheie or Scheie syndrome patients, who are treated by enzyme replacement therapy (ERT). Additionally, these findings might help determine whether therapies directed at reducing neuroinflammation and oxidative stress in MPS I could enhance neurological outcomes.
Study hypothesis: neuroinflammation and oxidative stress are present in MPS I subjects and are reflective of disease severity.
150 studies on the registry are indexed under Neuroinflammatory Diseases; 70 are open to participants now.
This study's enrollment of 30 is below the median of 100 across 52 observational studies indexed under Neuroinflammatory Diseases.
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20 subjects who have MPS I and are 6 years of age or older will be recruited for this study: 10 with severe MPS I (post-HCT Hurler syndrome); and 10 with attenuated MPS I (Hurler Scheie or Scheie syndrome, and receiving ERT).
In addition, 10 normal healthy controls, 6 years of age or older, will be recruited for this study.
MPS I participants must meet the following:
Healthy control participants must meet all of the following:
Exclusion Criteria:
Persons who have any of the following will not be enrolled in this study:
Participants who have MPS IH, also called Hurler syndrome
Participants who have either MPS IHS or MPS IS. MPS IHS is also called Hurler-Scheie syndrome. MPS IS is also called Scheie syndrome.
Age-matched healthy controls
Brain Magnetic Resonance Imaging/Magnetic Resonance Spectroscopy (MRI/MRS)
In a single session, each participant will undergo unsedated brain magnetic resonance imaging/magnetic resonance spectroscopy (MRI/MRS) to determine the presence and extent of any brain neuroinflammation. These data will be acquired on the 7-Tesla Siemens Prisma scanner at the Center for Magnetic Resonance Research (CMRR) at the University of Minnesota in Minneapolis.
Time frame: 1 day -Single encounter during an appointment which is set at time of study enrollment.
Presence and Level of Neuroinflammatory Biomarker MIP-1alpha
The presence of macrophage inflammatory protein (MIP)-1α (MIP-1alpha) will be determined; and if present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Regulated and Normal T cell Expressed and Secreted (RANTES)
The presence of 'regulated and normal T cell expressed and secreted' (referred to as RANTES), alternatively also known as chemokine (C-C motif) ligand 5, or CCL5, will be determined. If present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Tumor Necrosis Factor Alpha (TNF-α)
The presence of tumor necrosis factor alpha (TNF-α) will be determined. If present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interferon-gamma (IFN-γ)
The presence of interferon-gamma (IFN-γ) will be determined. If present, the level of this autoinflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 1 beta (IL1β)
The presence of interleukin 1 beta (IL1β) will be determined. If present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 2 (IL2)
The presence of interleukin 2 (IL2) will be determined. If present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Interleukin 8 (IL8)
The presence of interleukin 8 (IL8), alternatively referred to as chemokine (C-X-C motif) ligand 8, or CXCL8, will be determined. If present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Total Glutathione
The presence of total glutathione will be determined. If present, the level of this antioxidant will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Determination of Blood Glutathione Redox Ratio
The blood glutathione redox ratio will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Superoxide Dismutase (SOD)
The presence of superoxide dismutase (SOD) will be determined. If present, the level of this antioxidant will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of 8-isoprostane
The presence of 8-isoprostane will be determined. If present, the level of this inflammatory biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Levels of Thiobarbituric Acid Reactive Substances (TBARS)
The presence of thiobarbituric acid reactive substances (TBARS), which are biomarkers of the damage produced by oxidative stress, will be determined. If present, the levels of these biomarkers will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of 4-hydroxynonenal (4-HNE)
The presence of 4-hydroxynonenal (4-HNE) will be determined. If present, the level of this oxidative stress biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Presence and Level of Catalase
The presence of catalase will be determined. If present, the level of this oxidative stress biomarker will be determined.
Time frame: 1 day -Single blood draw performed at the same time as the single neuroimaging encounter.
Plan to share: Yes — De-identified individual data is input to the NIH-funded Rare Diseases Clinical Research Network's Data Management \& Coordinating Center ("DMCC"). Eventually this data will become part of the database of Genotypes and Phenotypes ("dbGaP"), which is part of the National Center for Biotechnology Information, U.S. National Library of Medicine.
Supporting information: Study protocol, Csr
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