Identifying blood biomarkers that reflect the metabolic changes occurring in people with amyotrophic lateral sclerosis (ALS) may be among the most promising approaches to diagnosing patients in the early stages of disease, sometimes years before motor symptoms appear, a review study suggests.
The study, “Importance of the serum biochemical parameters as potential biomarkers for rapid diagnosis and evaluating preclinical stage of ALS,” was published in the journal Medical Hypotheses.
ALS is neurological condition that causes damage to motor neurons, which are the nerve cells controlling voluntary movement. These neurons are progressively lost over the course of disease, causing motor symptoms that usually start as problems in speech and swallowing, muscle weakness, and stiffness, and eventually progresses to paralysis and extreme difficulty in swallowing or breathing.
Since symptoms of ALS overlap with those of many other neurological disorders, patients with the condition often need multiple rounds of testing before receiving a definite diagnosis of ALS, which can be delayed by more than a year.
That’s why there is a need for biomarkers that facilitate diagnosis and help identify these patients in the early stages, when treatments are most effective.
Metabolic changes in ALS seem to start before motor neurons are lost, suggesting that alterations in specific molecules of the metabolism — such as proteins, fats, or carbohydrates — may be helpful in diagnosing the condition.
While many biomarkers have been proposed, researchers believe that protein biomarkers in the blood would be the least costly and easiest to test, allowing for routine measurements that could identify patients before symptom onset.
“Overall, establishing biomarkers especially protein-based ones are necessary for accurate, cheap and rapid diagnosis for patients with ALS to prolong survival and develop therapeutic approaches at the pre-clinical stage,” the researchers wrote.
Duygu Aydemir and Nuriye Nuray Ulusu, professors at the Koç University, School of Medicine, and investigators at the Koç University Research Center for Translational Medicine, in Turkey, suggested cholesterol, creatinine, and albumin as the most promising blood biomarkers for detecting early metabolic changes in ALS patients.
Each of these biomarkers reflects specific changes that happen in ALS patients, such as muscle waisting (creatinine), increased inflammation (albumin), as well as increased fatty acid oxidation and decreased fat storages (cholesterol). Changes in the latter have been observed at least one decade before ALS diagnosis.
The researchers propose that these biomarkers can be used for the diagnosis of ALS “even in the pre-clinical stages of disease,” which may improve patients’ diagnosis, prognosis and assessment of therapies’ effects.
But the researchers advise that “further investigations related to indicated serum biochemical parameters should be performed via animal and human tests to be sure whether they can be used for ALS diagnosis and progression and in the preclinical phases.”
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