Pharmaceutical and biotech researchers convened last week to discuss their latest work on targeting neurodegenerative diseases
With all the news this year alone on progress being made with diagnostic testing for Alzheimer’s disease, clinical laboratory professionals will be interested to know that drug discovery efforts to combat neurogenerative diseases are also at a heightened pitch.
Last week at the one-day Neuroimmunology in Drug Discovery forum in Boston, scientists learned about the latest advances in therapeutic research to better treat Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. As the treatments advance, demand for them will increase, which goes hand-in-hand with medical lab testing to detect signs of these illnesses.
The concern is urgent. The US Food and Drug Administration (FDA) noted that 10% of people age 65 and older have Alzheimer’s disease, and that number could double by 2050. The FDA recently cleared the first in vitro diagnostics device that tests blood to diagnose Alzheimer’s, and other IVD manufacturers and clinical labs are working on other Alzheimer’s tests, Dark Daily reported.
“It’s looking quite promising for NLRP3 inhibitors,” said Cheryl Leyns, PhD, associate principal scientist in discovery neuroscience at Merck Research Laboratories, in discussing how mutations of the NLRP3 protein can lead to neurodegenerative diseases. (Photo copyright: ELRIG.)
Much of the discussion at the Neuroimmunology in Drug Discovery forum centered on the idea that neuroinflammation—in other words, inflammation of the brain or spinal cord—starts well before neurodegenerative diseases arise. Neuroinflammation can accelerate Parkinson’s disease and other neurodegenerative disorders, said Cheryl Leyns, PhD, associate principal scientist, neuroimmunology, at Merck Research Laboratories in Boston, who spoke at the event.
From that perspective, drug discovery researchers are on the prowl for these early signs of future problems.
Leyns discussed NLRP3, a protein that aids the body’s inflammation process. A mutation of NLRP3 can lead to inflammatory problems, making the protein a prime target for researchers. “We have been interested, in the biopharma space, in the potential of NLRP3 inhibitors,” she noted.
Older Immune Systems Are Susceptible
While many in the public correctly associate Alzheimer’s with a person being outwardly older, a lesser-known aspect is that the body’s immune system also ages, becoming more susceptible over time to chronic inflammation.
Wailings’ assertion was not rhetorical. She pointed to numbers which showed scholarly research that involved the terms “inflammation,” “neurodegeneration,” and “aging” was only about 17% of the total amount of journal articles that addressed the first two terms, but which did not include “aging.”
As the pharmaceutical, biotech, and medical fields move aggressively forward to defend people against neurodegenerative diseases like Alzheimer’s, clinical laboratory scientists should take comfort that diagnostic testing trends are solidly in the mix.
Therapeutic advances, along with increased options for testing, show promising signs that patients and their caregivers will have more tools to use in the battle against these illnesses.
Study is expected to result in new clinical laboratory test biomarkers based on proteins shown to be associated with specific diseases
In January, the UK Biobank announced the launch of the “world’s most comprehensive study” of the human proteome. The study focuses on proteins circulating throughout the human body. Researchers involved in this endeavor hope the project will transform disease detection and lead to clinical laboratory blood tests that help diagnosticians identify illnesses earlier than with conventional diagnostics.
Building on the results of a 2023 pilot project that studied “the effects of common genetic variation on proteins circulating in the blood and how these associations can contribute to disease,” according to a UK Biobank news release, the 2025 UK Biobank Pharma Proteomics Project (UKB-PPP) plans to analyze up to 5,400 proteins in 600,000 samples to explore how an individual’s protein levels changes over time and how those changes may influence the existence of diseases in mid-to-late life.
The specimens being analyzed include 500,000 samples extracted from UK Biobank participants and an additional 100,000 set of second samples taken from volunteers up to 15 years later.
“The data collected in the study will allow scientists around the world to conduct health-related research, exploring how lifestyle, environment, and genetics lead through proteins to some people developing particular diseases, while others do not,” Sir Rory Collins, FMedSci FRS, professor of medicine and epidemiology at University of Oxford and principal investigator and chief executive of the UK Biobank, told The Independent.
“That will allow us to identify who it is, who’s likely to develop disease well before they do, and we can then look at ways in which to prevent those conditions before they develop,” he added.
“It really might be possible to develop simple blood tests that can detect disease much earlier than currently exists,” said Naomi Allen, MSc, DPhil (above), chief scientist for UK Biobank and professor of epidemiology at Oxford Population Health, University of Oxford, in an interview with The Independent. “So, it adds a crucial piece in the jigsaw puzzle for scientists to figure out how disease develops and gives us firm clues on what we can do to prevent and treat it.” Clinical laboratories may soon have new test biomarkers that help identify proteins associated with specific diseases. (Photo copyright: UK Biobank.)
Developing New Protein-based Biomarkers
A proteome is the entire set of proteins expressed by an organism, cell, or tissue and the study of the proteome is known as proteomics. The proteome is an expression of an organism’s genome, but it can change over time between cell types and growth conditions.
The human genome contains approximately 20,000 genes and human cells have between 80,000 and 400,000 proteins with specific cells having their own proteomes. Proteomics can help ascertain how proteins function and interact with each other and assist in the identification of biomarkers for new drug discoveries and development.
“This is hugely valuable, because it will enable researchers to see how changes in protein levels within individuals over mid- to late-life influence the development of a whole range of different diseases,” said Naomi Allen, MSc, DPhil, chief scientist for UK Biobank and professor of epidemiology at the Oxford Population Health, University of Oxford, in The Independent. “It will accelerate research into the causes of disease and the development of new treatments that target specific proteins associated with those diseases.
“The pilot data is already showing that specific proteins are elevated in those who go on to develop many different types of cancers up to seven years before a clinical diagnosis is made. And for dementia, up to 10 years before clinical diagnosis is made,” she added.
According to the project’s website, the UK Biobank’s proteomics dataset will allow researchers to:
Examine proteomic and genetic data from half a million people to provide a more detailed picture of the biological processes involved in disease progression.
Examine how and why protein levels change over time to understand age-related changes in healthy individuals.
Utilize proteomic data together with imaging data to understand disease mechanisms.
“Data from the pilot study has shown that specific proteins are substantially elevated in individuals with autoimmune conditions like multiple sclerosis and Crohn’s disease and so on,” Allen noted. “So, you can see how a simple blood test could be used to complement existing diagnostic measures in order to diagnose these types of diseases more accurately and perhaps more quickly.”
An Invaluable Resource of Knowledge
The initial UK Biobank started in 2006 and, to date, has collected biological and medical data from more than half a million individuals. The subjects of the UKB-PPP study are between the ages of 40 and 69 and reside in the UK. The database is globally accessible to approved researchers and scientists engaging in research into various diseases.
The full dataset of the latest research is expected to be added to the UK Biobank Research Analysis Platform by the year 2027. The newest study is backed by a consortium of 14 pharmaceutical firms.
Allen also noted that evidence from the research has emphasized how some drugs may be useful in treating a variety of conditions.
“Some proteins that are known to be important for immunity are related to developing a range of psychiatric conditions like schizophrenia, depression, bipolar disorder and so on,” she told The Independent. “And given there are drugs already available that specifically target some of these proteins that are used for other conditions, it presents a real opportunity for repurposing those existing drugs for these neuropsychiatric conditions.”
This type of comprehensive study of the human proteome may have a great impact on patient diagnosis and treatment once the study is completed and the results are disclosed.
“The data will be invaluable. The value of the data is infinite,” Collins told The Independence.
Since it is clinical laboratories that will be engaged in testing for proteins that have become associated with specific diseases, this new UK Biobank study has the potential to expand knowledge about useful protein markers for both diagnosis and therapeutic solutions (prescription drugs).
Findings may lead to new clinical laboratory biomarkers for predicting risk of developing MS and other autoimmune diseases
Scientists continue to find new clinical laboratory biomarkers to detect—and even predict risk of developing—specific chronic diseases. Now, in a recent study conducted at the University of California San Francisco (UCSF), researchers identified antibodies that develop in about 10% of Multiple Sclerosis (MS) patients’ years before the onset of symptoms. The researchers reported that of those who have these antibodies, 100% develop MS. Thus, this discovery could lead to new blood tests for screening MS patients and new ways to treat it and other autoimmune diseases as well.
The UCSF researchers determined that, “in about 10% [of] cases of multiple sclerosis, the body begins producing a distinctive set of antibodies against its own proteins years before symptoms emerge,” Yahoo Life reported, adding that “when [the patients] are tested at the time of their first disease flare, the antibodies show up in both their blood and cerebrospinal fluid.”
That MS is so challenging to diagnose in the first place makes this discovery even more profound. And knowing that 100% of a subset of MS patients who have these antibodies will develop MS makes the UCSF study findings quite important.
“This could be a useful tool to help triage and diagnose patients with otherwise nonspecific neurological symptoms and prioritize them for closer surveillance and possible treatment,” Colin Zamecnik, PhD, scientist and research fellow at UCSF, told Yahoo Life.
“From the largest cohort of blood samples on Earth, we obtained blood samples from MS patients years before their symptoms began and profiled antibodies against self-autoantibodies that are associated with multiple sclerosis diagnosis,” Colin Zamecnik, PhD (above), scientist and research fellow at UCSF, told Yahoo Life. “We found the first molecular marker of MS that appears up to five years before diagnosis in their blood.” These findings could lead to new clinical laboratory tests that determine risk for developing MS and other autoimmune diseases. (Photo copyright: LinkedIn.)
UCSF Study Details
According to the MS International Foundation Atlas of MS, there are currently about 2.9 million people living with MS worldwide, with about one million of them in the US. The disease is typically diagnosed in individuals 20 to 50 years old, mostly targeting those of Northern European descent, Yahoo Life reported.
To complete their study, the UCSF scientists used the Department of Defense Serum Repository (DoDSR), which is comprised of more than 10 million individuals, the researchers noted in their Nature Medicine paper.
From that group, the scientists identified 250 individuals who developed MS, spanning a period of five years prior to showing symptoms through one year after their symptoms first appeared, Medical News Today reported. These people were compared to 250 other individuals in the DoDSR who have no MS diagnosis but who all had similar serum collection dates, ages, race and ethnicities, and sex.
“The researchers validated the serum results against serum and cerebrospinal fluid results from an incident MS cohort at the University of California, San Francisco (ORIGINS) that enrolled patients at clinical onset. They used data from 103 patients from the UCSF ORIGINS study,” according to Medical News Today. “They carried out molecular profiling of autoantibodies and neuronal damage in samples from the 500 participants, measuring serum neurofilament light chain measurement (sNfL) to detect damage to nerve cells.
“The researchers tested the antibody patterns of both MS and control participants using whole-human proteomeseroreactivity which can detect autoimmune reactions in the serum and CSF,” Medical News Today noted.
Many who developed MS had an immunogenicity cluster (IC) of antibodies that “remained stable over time” and was not found in the control samples. The higher levels of sNfL in those with MS were discovered years prior to the first flare up, “indicating that damage to nerve cells begins a long time before symptom onset,” Medical News Today added.
“This signature is a starting point for further immunological characterization of this MS patient subset and may be clinically useful as an antigen-specific biomarker for high-risk patients with clinically or radiologically isolated neuroinflammatory syndromes,” the UCSF scientists wrote in Nature Medicine.
“We believe it’s possible that these patients are exhibiting cross reactive response to a prior infection, which agrees with much current work in the literature around multiple sclerosis disease progression,” Zamecnik told Yahoo Life.
It “validates and adds to prior evidence of neuro-axonal injury occurring in patients during the MS preclinical phase,” the researchers told Medical News Today.
Implications of UCSF’s Study
UCSF’s discovery is a prime example of technology that could soon work its way into clinical use once additional studies and research are done to support the findings.
The researchers believe their research could lead to a simple blood test for detecting MS years in advance and discussed how this could “give birth to new treatments and disease management opportunities,” Neuroscience News reported.
Current MS diagnosis requires a battery of tests, such as lumbar punctures for testing cerebrospinal fluid, magnetic resonance imaging (MRI) scans of the spinal cord and brain, and “tests to measure speed and accuracy of nervous system responses,” Medical News Today noted.
“Given its specificity for MS both before and after diagnosis, an autoantibody serology test against the MS1c peptides could be implemented in a surveillance setting for patients with high probability of developing MS, or crucially at a first clinically isolated neurologic episode,” the UCSF researchers told Medical News Today.
The UCSF discovery is another example of nascent technology that could work its way into clinical use after more research and studies. Microbiologists, clinical laboratories, and physicians tasked with diagnosing MS and other autoimmune diseases should find the novel biomarkers the researchers identified most interesting, as well as what changed with science and technology that enabled researchers to identify these biomarkers for development.
The Technion breathalyzer would give pathology groups and medical laboratories unprecedented ability to support physicians in diagnosing and treating cancers, chronic diseases, and other illnesses
Readers of Dark Daily know that several pathology research teams in America and the UK are developing breath analyzer tests that can detect everything from lung cancer to early-stage infections. Clinical laboratories will soon have a plethora of breath-related tests from which to choose. Now there’s a new kid on the block. A breathalyzer test that can detect up to 17 distinct cancerous, inflammatory, and neurological diseases!
Assuming the cost per test was at a competitive level to existing technologies, what would give this new diagnostic system appeal to physicians and patients alike is that it would be a non-invasive way to diagnose disease. Only a sample of the patient’s breath would be needed to perform the assays.
Researchers at the Israel Institute of Technology, or Technion, published the results of their study in ACS Nano, a monthly journal of the American Chemical Society devoted to “nanoscience and nanotechnology research at the interfaces of chemistry, biology, materials science, physics, and engineering.” (more…)
A university research team and a global diagnostics company simultaneously but independently unveil two new tests that accurately identify people predisposed to Alzheimer’s at earlier stages in the disease
Medical laboratory scientists and clinical pathologists have long awaited an accurate and clinically-useful test for the predisposition and early diagnosis of Alzheimer’s disease. Now comes pioneering efforts from two organizations that suggest real progress is being made.
One organization is an academic center and the other is anin vitro company. It was a research team at Rowan University School of Osteopathic Medicine (RowanSOM) that announced development of the first blood test to use the body’s own immune system to detect mild cognitive impairment (MCI), an early stage of Alzheimer’s disease.
