Muscle Waste Product Creatinine Might Be Used as SBMA Biomarker, Study Reports

Muscle Waste Product Creatinine Might Be Used as SBMA Biomarker, Study Reports
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Creatinine as a biomarker

Blood levels of a waste product from muscle metabolism could be used to see how spinal and bulbar muscular atrophy (SBMA) develops before symptoms appear, a Japanese study reports.

The research on the waste product, creatinine, appeared in the journal Neurology. The title of the article is “Biomarker-based analysis of preclinical progression in spinal and bulbar muscular atrophy.

Scientists have been trying to find biomarkers that can spot neurodegenerative disorders before symptoms appear. The work has led to promising biomarkers for Alzheimer’s and Huntington’s disease.

But little research has been done on biological changes over time that occur before neurodegenerative disease symptoms show up. SBMA is a neurodegenerative disease caused by a mutation of the androgen receptor gene.

The Japanese researchers had previously reported a link between levels of the creatinine that kidneys secrete to the blood and the severity of movement problems once SBMA symptoms appear. But the team had not looked at how creatinine levels change before symptoms show up.

They wondered if tracking changes in biochemical levels and body measurements before SBMA symptoms appeared could shed light on how it develops. They focused on changes before and after the start of patients’ muscle weakness.

The team used statistical methods to predict changes in disease markers. Then they  compared the forecasts with changes in healthy men and in ALS and Parkinson’s patients. In addition, they analyzed the link between patients’ creatinine blood levels and the start of their symptoms.

Their study between October 2014 and October 2017 involved 40 men with SBMA, 25 with ALS, 20 with Parkinson’s, and 48 healthy controls. The SBMA patients, whose bulbar and limb muscles had weakened, were followed for a mean of 17.3 years, including 11.4 years before symptoms appeared.

A key finding was a 10-year decrease in blood creatinine levels before symptoms appeared. The mean creatinine level was almost two-thirds lower in SBMA patients when symptoms appeared than it was in healthy controls.

Before symptoms showed up, SBMA patients also displayed a tendency toward increased blood levels of the enzymes alanine transaminase and aspartate transaminase, which can indicate liver damage. No changes were observed in ALS or Parkinson’s patients.

The start of SBMA symptoms had little effect on the rate at which patients’ creatinine was decreasing, the researchers reported. Two reasons why creatinine levels drop are loss of muscle mass and a decrease in levels of a creatinine precursor known as creatine.

The SBMA patients did not have changes in body mass after developing muscle weakness, however.

“Our results thus indicate that serum creatinine level is a potential biomarker for evaluating disease progression during the preclinical [pre-symptom] stage of SBMA,” the researchers wrote.

Doctors use blood creatinine levels to assess a number of health concerns, so the test’s availability is not a problem, the researchers said.

Because SBMA is a hereditary disease, “monitoring the serum creatinine level for individuals at risk of developing SBMA enables the detection of preclinical disease progression and therapeutic intervention,” they said.

The team said more studies need to be done to confirm their results.

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