Rare Disease Report

Positive Results Found in Study of GAGs in Leukocytes in MPS VI Patients

FEBRUARY 27, 2018
Mathew Shanley
Yesterday, positive outcomes were reported from a biomarker study evaluating intracellular glycosaminoglycans (GAGs) levels in leukocytes as a disease activity biomarker in MPS VI.

The biomarker study, conducted at UCSF Benioff Children’s Hospital in Oakland, California and analyzed by the Greenwood Genetic Center Biochemical Genetics Laboratory in South Carolina, has supported the development of a new and robust quantification method of intracellular heparin sulfate (HS), chondroitin sulfate (CS) and dermatan sulfate (DS) in leukocytes (lekoGAGs).

MPS VI, commonly referred to as Maroteaux-Lamy syndrome, is a lysosomal disorder due to a deficiency in or complete absence of the arylsulfatase B enzyme, which can lead to a toxic accumulation of GAGs. The most common symptoms of the condition include: coarse facial features, corneal clouding, joint abnormalities and skeletal malformations, hepatosplenomegaly, and hearing loss.

Current standard-of-care for MPS VI is the ERT galsulfase (Naglazyme), but patients can also be treated with hematopoietic stem cell transplant (HSCT).

The study, led by Dr Paul R. Harmatz, enrolled 12 subjects, including 6 MPS VI patients between the ages of 6 and 14 years who have been treated with galsulfase for 10 ± 3.1 years, and 6 age-matched control subjects not diagnosed with MPS.

Harmatz and his team of researchers measured urinary GAGs (uGAGs) and leukoGAGs and discovered that all MPS VI patients receiving enzyme replacement therapies (ERTs) have total uGAGs higher than the upper limit of normal and leukoGAGs above control subjects values.

The most profuse GAG components in MPS VI patients receiving ERT are DS and CS in urine and CS in leukocytes, respectively, both of which can be reduced with odiparcil, which is in development by the French biopharmaceutical company Inventiva and was granted orphan drug designation by the U.S. Food and Drug Administration (FDA) in August.

"The high level of leukoGAG in patients receiving ERT is a clear signal of the limitations of this therapeutic strategy,” said Dr Paul R. Harmatz, the principal investigator of this study in a press release. “Our ability to use a new and robust quantification method to measure intracellular HS/CS/DS will enrich our analysis of the Phase IIa iMProveS trial and are suggestive of the high medical need that can be addressed by odiparcil."

Additionally, the study results provided data on the arylsufatase B activity in leukoGAGS, and showed that 60 minutes after completion of galsulfase infusion, enzyme activity is increased nearly 8 times from baseline. The CS content in leukoGAGs, however, remains more than 12-fold above baseline.

For more stories pertaining to lysosomal storage diseases, follow Rare Disease Report on Facebook and Twitter.
 

Stay informed on the latest rare disease news and developments by signing up for our newsletter.
Copyright © RareDR 2013-2018 Rare Disease Communications. All Rights Reserved.