Could a New ALS Blood Test Reform Diagnosis?

Karena Peterson, 9/29/24

When a patient is diagnosed with Amyotrophic Lateral Sclerosis, or ALS, they are given a dire prognosis with devastatingly no cure. As this neurodegenerative disorder progresses, the patient will switch from experiencing early symptoms, such as weakness in arms and legs and trouble with speech, to more severe symptoms of breathing difficulties, weight loss, and inability to stand. As the symptoms get more severe, the life expectancy for the patient will drastically shorten, being around 3-5 years after an ALS diagnosis, though it can vary. While medications do exist, they can only slow the inevitable progression of the disease, or partially reduce nerve damage. These medications cannot cure or eradicate damage that has already been dealt. Thus, there is a need for early diagnosis; catching the disease as soon as possible allows for the earliest treatment, and delay of symptoms, as possible. Yet, the identification of ALS can take up to a year of a magnitude of various tests. So, when there are not just one, but two, new, promising research publications, they hold a lot of prospects.

Why There is a Need

Looking at current diagnosis methods, it is apparent why these new research results hold so much significance. Usually, a combination of family history, genetic testing, imaging biomarkers, and many specialist opinions are used. However, the diagnosis process can take a long period of time, seemingly longer when each day further deteriorates a patient's condition. Additionally, it can be difficult to find results during the patient's life, as some (but notably, few) diagnosis methods are invasive and risky.

Tau and TDP-43 Biomarkers

TDP-43, or transactive response DNA binding protein of 43 kDa, is a protein involved in gene expression regulation, found in the cell’s nucleus. Tau is a protein that is a structural component of all cells- including neurons. Tau has already been linked in the past with dementia. Now, it appears the levels of tau and TDP-43 in vesicles, or tiny lipid sacs, within the bloodstream can not only help diagnose ALS, but also frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP). These are all neurodegenerative diseases, with severe, debilitating prognoses.

Typically, brain tissue has to be examined for tau and TDP-43, making diagnoses by these proteins difficult. Yet, this study on this non-invasive testing, conducted with 991 individuals (some of which with the three listed diseases, and others a control group of healthy patients) may change this fact.

While this will work well in helping narrow down the causes of the symptoms- symptoms that usually apply to many conditions, further complicating the matter, experts do not predict this test to replace a clinical diagnosis. This diagnosis tool will, however, assist in reducing the possibilities.

Overall, these blood biomarkers create a better, and hopefully faster way of diagnosing not just ALS, but two other neurological diseases, leading to quicker research progression, treatment, and diagnosis.

MicroRNA

MicroRNA is a type of RNA that is smaller than many other types. These can bind to messenger RNA to block them from making proteins, and, with this recent research, speed diagnosis of ALS.

Through a series of research experiments, scientists from Brian Chemistry Labs, a non-profit institute, have found a unique fingerprint of eight microRNA sequences within the bloodstream. These are distinct and can help identify ALS.

An issue that also occurs with diagnosing ALS- outside of delays- is misdiagnoses. The rate of which ALS is misdiagnosed as other diseases that share similar properties is up to 68%. However, these biomarkers are able to distinguish patients of ALS from patients with similar conditions, Primary Lateral Sclerosis and Parkinson’s Disease, with an overall accuracy of up to 98%.

Similar to the first, this isn’t meant to replace clinical tests, but rather act as a quick secondary test to confirm diagnosis. This can provide confirmatory information quickly, helping to speed diagnosis. The organization is currently working on a patent and ensuring it is available for FDA approval. Assuming the best-case scenario, developing and marketing will only take 18 months, bringing this new research closer.

Overall

Currently, diagnosing ALS can be tricky, with misdiagnosis and long processes lengthening the matter. However, usage of blood biomarkers, tau, TDP-43, and microRNA, can change that. These tests are promising, but it is important to note that there are still issues and steps that need to be taken before they can be commonly used by doctors. Still, these non-invasive blood tests hold the future of a quicker, more accurate diagnosis of Amyotrophic Lateral Sclerosis.

Sources

ALS Association, "Obtaining an ALS Diagnosis"

https://www.als.org/navigating-als/resources/obtaining-als-diagnosis

Biomed Central, "TDP-43 Pathology in Alzheimer’s Disease"

https://molecularneurodegeneration.biomedcentral.com/articles/10.1186/s13024-021-00503-x

Brain Communications, "A microRNA diagnostic biomarker for amyotrophic lateral sclerosis"

https://academic.oup.com/braincomms/article/6/5/fcae268/7754324?login=false

Cleveland Clinic, "Amyotrophic Lateral Sclerosis"

https://my.clevelandclinic.org/health/diseases/16729-amyotrophic-lateral-sclerosis-als

Healthline, "Understanding Tau Protein and Its Role in Alzheimer’s Disease"

https://www.healthline.com/health/alzheimers/tau-protein-in-alzheimers-disease

Medical Life Sciences News, "Simple blood test will help neurologists to make a definitive and rapid diagnosis of ALS"