Glutamate dehydrogenase (GLDH) can be a specific biomarker of liver injury in patients with Duchenne muscular dystrophy (DMD), according to results from a phase 2 clinical trial that were published in the journal Biomarkers in Medicine.
There is an unmet need for biomarkers of disease progression in DMD as well as a lack of biomarkers to monitor the health of patients’ livers, the authors said.
DMD patients are prone to drug-induced liver injury but serum enzymes such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), which are commonly used as markers of liver injury, are not suitable in DMD. They are secreted from skeletal muscles and are already elevated in these patients.
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The aim of the study was to evaluate the use of GLDH and cardiac troponin I as safety biomarkers. Muscle injury panel (sTnI, FABP3, CK muscle type, and Myl3) and creatine kinase (CK) were evaluated as biomarkers of muscle health.
Francesco Muntoni, professor of pediatric neurology at the University College London Institute of Child Health and Great Ormond Street Hospital for Children in the UK led a team of researchers. They collected data during a phase 2 trial of domagrozumab in ambulatory males with DMD, aged from 6 to less than 16 years.
They found that there was no strong correlation between GLDH and ALT or AST and CK. This suggested that GLDH levels were not affected by muscle injury. They concluded that GLDH may be a more specific biomarker to monitor liver injury in patients with DMD than ALT.
“Elevations observed in cardiac troponin I did not predict a greater decline in cardiac function by left-ventricular ejection fraction,” the authors said. “CK correlated significantly with sTnI, FABP3, CK muscle type, and Myl3.”
They suggested that muscle injury panels do not seem to be more sensitive than CK in detecting muscle injury in DMD patients.
GLDH is a mitochondrial enzyme that is emerging as a liver biomarker specific to injury. It converts glutamate into α-ketoglutarate and is primarily found in liver cells and almost none in skeletal muscles. Preclinical studies have demonstrated the specificity of GLDH for liver injury.
Wagner KR, Guglieri M, Ramaiah SK, et al. Safety and disease monitoring biomarkers in Duchenne muscular dystrophy: results from a Phase II trial. Biomark Med. Published online September 17, 2021. doi: 10.2217/bmm-2021-0222