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Can Cell-Free DNA Spot It Early?


Simple blood test using cell-free DNA may enable faster, more accurate ALS diagnosis and earlier treatment.

A new study has revealed that a noninvasive blood test analyzing cell-free DNA could significantly improve the speed and accuracy of diagnosing amyotrophic lateral sclerosis (ALS ) (1 Trusted Source
Innovative Blood Test Shows Potential for Early ALS Detection

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By detecting fragments of DNA released from dying cells, this approach may help neurologists distinguish ALS from other neurological disorders and identify the disease earlier, allowing for timelier interventions and potentially longer survival.

The research, published in Genome Medicine, is the first to evaluate cell-free DNA as a biomarker for ALS.

Understanding ALS and Its Urgency for Early Detection

Commonly known as Lou Gehrig’s disease, amyotrophic lateral sclerosis (ALS) is a rare and currently incurable neurodegenerative disease that causes the loss of motor neurons in the brain and spinal cord.

ALS onset typically begins in patients who are 50-70 years old, with life expectancy being only two to five years after initial diagnosis, according to the National Institutes of Health. While ALS is rare in people ages 40 or younger, earlier diagnosis can provide higher life expectancy, thus prompting neurologists to find a way to better predict onset and disease intensity.

The Need for Reliable ALS Biomarkers

“There is an urgent need for a biomarker in ALS to diagnose patients more quickly, support clinical trials and monitor disease progression,” said the study’s lead author Dr. Christa Caggiano, a postdoctoral fellow at UCLA Health’s Neurology Department. “Our study presents cell-free DNA, combined with a machine learning model, as a promising candidate to fill this gap.”

Cell-Free DNA May Hold the Key

Caggiano and fellow UCLA Health researchers, along with their collaborators at the University of Queensland, tested cell-free DNA as an ALS biomarker because it releases from dying cells in different body tissues affected by the disease and has distinct signatures.

These signatures are caused by the natural process of DNA methylation, which occurs when a methyl group molecule attaches to DNA and helps to regulate expression of genes.

ALS leads to changes both in the amount of cell-free DNA released from degenerating cells as well as patterns of methylation.

In the study, Caggiano tested this method on two groups of ALS patients and healthy participants. Computer models tested to see if these DNA signals could predict which patients had ALS and who was healthy. The test was able to significantly discriminate between ALS patients and healthy participants and was able to provide insights into disease severity.

“Our model test could not only distinguish ALS patients from healthy individuals but also from those with other neurological conditions, which is a challenge for current ALS biomarkers,” Caggiano said. “We hope this could lead to faster diagnoses and better predictions of patient outcomes.”

A Broader View of ALS Beyond Nerve Cells

Caggiano said an advantage of this test is that it examines cell-free DNA from several tissue types and not just nerve cells. The test was able to pick up signals from dying muscle tissue and inflammation, suggesting that ALS may also affect muscle tissues and immune cells.

While the biomarker test shows promise, Caggiano said larger studies with more diverse participants and testing methods are needed before it can be relied on in clinical settings.

UCLA Health is currently conducting a larger trial in conjunction with other research institutions to attempt to validate this biomarker test.

Reference:

  1. Innovative Blood Test Shows Potential for Early ALS Detection – (https://bioengineer.org/innovative-blood-test-shows-potential-for-early-als-detection/)

Source-University of California – Los Angeles Health Sciences

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