Intrathecal enzyme replacement for Hurler syndrome: biomarker association with neurocognitive outcomes.
Genet Med
; 21(11): 2552-2560, 2019 11.
Article
in En
| MEDLINE
| ID: mdl-31019279
ABSTRACT
PURPOSE:
Abnormalities in cerebrospinal fluid (CSF) have been reported in Hurler syndrome, a fatal neurodegenerative lysosomal disorder. While no biomarker has predicted neurocognitive response to treatment, one of these abnormalities, glycosaminoglycan nonreducing ends (NREs), holds promise to monitor therapeutic efficacy. A trial of intrathecal enzyme replacement therapy (ERT) added to standard treatment enabled tracking of CSF abnormalities, including NREs. We evaluated safety, biomarker response, and neurocognitive correlates of change.METHODS:
In addition to intravenous ERT and hematopoietic cell transplantation, patients (N = 24) received intrathecal ERT at four peritransplant time points; CSF was evaluated at each point. Neurocognitive functioning was quantified at baseline, 1 year, and 2 years posttransplant. Changes in CSF biomarkers and neurocognitive function were evaluated for an association.RESULTS:
Over treatment, there were significant decreases in CSF opening pressure, biomarkers of disease activity, and markers of inflammation. Percent decrease in NRE from pretreatment to final intrathecal dose posttransplant was positively associated with percent change in neurocognitive score from pretreatment to 2 years posttransplant.CONCLUSION:
Intrathecal ERT was safe and, in combination with standard treatment, was associated with reductions in CSF abnormalities. Critically, we report evidence of a link between a biomarker treatment response and neurocognitive outcome in Hurler syndrome.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Injections, Spinal
/
Mucopolysaccharidosis I
/
Enzyme Replacement Therapy
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Language:
En
Journal:
Genet Med
Journal subject:
GENETICA MEDICA
Year:
2019
Document type:
Article
Affiliation country:
Estados Unidos