Health

Diagnostic marker found for deadly brain dise

Photo: Kanta Horie, PhD, (left) and Chihiro Sato, PhD, discuss data at the Tracy Family SILQ Center at Washington University School of Medicine in St. Louis. Sato and Hori led a team that discovered a biomarker for a rare and fatal brain disease known as corticobasal degeneration (CBD). The biomarker could accelerate efforts to develop treatments for CBD.
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Credit: Matt Miller/University of Washington

Zooming in on a single disease and studying it extensively is often the most productive path to finding cures. But there’s no easy way to distinguish between people who have any of the primary taupathies — a group of rare brain diseases characterized by rapidly worsening problems with thinking and movement — because the symptoms are so similar. As a result, most studies of Taupathy protopathies have included a combination of these diseases, even though researchers know that the diseases differ in important ways and may require different treatments.

Now, however, researchers at Washington University School of Medicine in St. Louis have found a biomarker that identifies with up to 89% accuracy people with a primary comorbidity called cortical-basal degeneration (CBD). The researchers said that traditional diagnostic methods for CBD are only 25% to 50% accurate.

The scientists said the biomarker could be developed into a tool for screening potential volunteers for CBD research studies and clinical trials and, eventually, to identify people who could benefit from CBD therapies.

The study was published on November 24 in Nature medicine.

“Before, the only way to find out which primary taupathy was a person had to wait until they died and then examine the person’s brain under a microscope,” said co-senior author Chihiro Sato, PhD, assistant professor of neurology. “The patient comes in with stiffness, balance issues, speech and memory problems, and it could be CBD, but it could also be progressive supranuclear palsy (PSP), Alzheimer’s disease, or other diseases. This biomarker can identify people with CBD.” reliably, which means we can use it to enroll people in clinical trials. And, in the future, it may be the key to starting treatment.”

CBD is one of about two dozen brain diseases that are considered tauopathies because they share one crucial feature: toxic tau clumps in the brain. Individual taupopathies involve different subtypes of tau and show different patterns of damage to brain cells and tissues. The different sets of symptoms of Taupopathy overlap, making it difficult for doctors to distinguish one from the other. This complicates efforts to study them and find a cure.

Taupopathies are classified as either primary or secondary, depending on when the tau tangle appears in the course of the disease. In primary tauinopathies, tau tangles form initially, apparently on their own. In secondary taupopathies, tangles do not form until other changes have occurred in the brain. For example, in Alzheimer’s disease, the most common secondary tauopathy, amyloid-beta protein builds up in the brain for years before tau tangles appear.

In 2020, Kanta Hori, associate professor of neuroscience and first author on the current paper, developed a highly sensitive technique for detecting specific parts of tau in the cerebrospinal fluid that surrounds the brain and spinal cord. Horry and colleagues used this technique to identify a new form of tau in Alzheimer’s patients, and showed that the level of new tau in cerebrospinal fluid indicates the stage of the disease, and tracks the amount of tau tangles in the brain.

As part of this study, Horie, Sato, and their colleagues–including co-senior author Randall G. Bateman, MD, Charles F. and Joanne Knight Distinguished Professor of Neurology–used this technique to search for distinct forms of tau associated with primary Taupopathies. . To ensure that study subjects were accurately classified, Hori, Sato, and Bateman collaborated with co-authors Adam Boxer, MD, PhD, Salvatore Spina, MD, PhD, and Lorne VanDeVried, MD, PhD, all in the Department of Neuroscience at UCSD. , San Francisco. The team examined brain tissue and cerebrospinal fluid from people who died of dementia and movement disorders, and their specific illnesses were confirmed at autopsy. The study population included subjects with one of five primary comorbid diseases – CBD; PSP. frontotemporal lobar degeneration with microtubule-associated tau protein (FTLD-MAPT) mutations; agyrophilic grain disease. and Pick’s disease – as well as Alzheimer’s disease and dementia unrelated to tau. For comparison, they also examined samples from people without dementia.

Two specific forms of tau — the microtubule-binding region (MTBR)-275 and MTBR-tau 282 — were unusually high in the brains and low in the cerebrospinal fluid of patients with CBD and a subset of FTLD-MAPT. Further investigation showed that these forms of tau differentiate people with CBD from those with other primary taupathies by 84% to 89%, depending on the disease.

“Even if there is an experimental drug available that specifically targets the tau variant of CBD, it is very difficult to test without a biomarker,” Horry said. “A trial may fail even when a drug works if the population is heterogeneous. Trials of drugs that specifically target the tau type of CBD could be improved by correctly enrolling diagnosed patients. Having a biomarker opens the way for drug companies to improve trials.” Clinical and Accelerating Research toward CBD Therapies.”

Several experimental drugs targeting tau are in the pipeline. Most are designed with Alzheimer’s patients in mind, but they may be effective as treatments for primary Taupathy. The researchers said that Horry’s technique could be used to find biomarkers for other primary taupopathies, opening the door for more clinical trials.

“CBD patients and families urgently need effective therapies, but it has been challenging to organize clinical trials for this deadly disease,” Boxer said. Until now, we did not have a specific biomarker to accurately diagnose patients. This new biomarker also opens the door to testing several new tau-directed therapies for CBD, as it may allow us to directly measure the ability of these therapies to lower toxic tau protein levels in patients’ brains.”


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Source: news.google.com

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