MRS to Determine Neuroinflammation and Oxidative Stress in MPS I

University of Minnesota (UMN)

Status: Completed

Conditions: Mucopolysaccharidosis Type I

Study type: Observational

Funder types: Other; NETWORK; NIH

Identifiers

NCT03576729

U54NS065768 (U.S. NIH Grant/Contract)

STUDY00003680

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 30 patients

Sex: All

Ages: 6+ years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

MPS I participants must meet the following:

1. Diagnosis of Hurler syndrome, OR Hurler-Scheie syndrome, OR Scheie syndrome
2. 6 years of age or older at time of screening

Healthy control participants must meet all of the following:

1. Absence of neurological disorder
2. 6 years of age or older at time of screening

Exclusion criteria

Persons who have any of the following will not be enrolled in this study:

1. Any surgically implanted pacemaker
2. Any indwelling electronic device, including programmable shunts
3. Orthodontic braces, unless non-metallic
4. Other implanted metal in the body other than titanium
5. An inability or unwillingness to complete an MRI/MRS because of low cognitive function or behavioral dysregulation
6. Pregnancy

Trial design

30 participants in 3 patient groups

Hurler syndrome participants

Description:

Participants who have MPS IH, also called Hurler syndrome

Hurler-Scheie/Scheie participants

Description:

Participants who have either MPS IHS or MPS IS. MPS IHS is also called Hurler-Scheie syndrome. MPS IS is also called Scheie syndrome.

Healthy Controls

Description:

Age-matched healthy controls