These advances in the battle against cancer could lead to new clinical laboratory screening tests and other diagnostics for early detection of the disease
As Dark Daily reported in part one of this story, the World Economic Forum (WEF) has identified 12 new breakthroughs in the fight against cancer that will be of interest to pathologists and clinical laboratory managers.
As we noted in part one, the WEF originally announced these breakthroughs in an article first published in May 2022 and then updated in October 2024. According to the WEF, the World Health Organization (WHO) identified cancer as a “leading cause of death globally” that “kills around 10 million people a year.”
The WEF is a non-profit organization base in Switzerland that, according to its website, “engages political, business, academic, civil society and other leaders of society to shape global, regional and industry agendas.”
Monday’s ebrief focused on four advances identified by WEF that should be of particular interest to clinical laboratory leaders. Here are the others.
Personalized Cancer Vaccines in England
The National Health Service (NHS) in England, in collaboration with the German pharmaceutical company BioNTech, has launched a program to facilitate development of personalized cancer vaccines. The NHS Cancer Vaccine Launch Pad will seek to match cancer patients with clinical trials for the vaccines. The Launch Pad will be based on messenger ribonucleic acid (mRNA) technology, which is the same technology used in many COVID-19 vaccines.
The BBC reported that these cancer vaccines are treatments, not a form of prevention. BioNTech receives a sample of a patient’s tumor and then formulates a vaccine that exposes the cancer cells to the patient’s immune system. Each vaccine is tailored for the specific mutations in the patient’s tumor.
“I think this is a new era. The science behind this makes sense,” medical oncologist Victoria Kunene, MBChB, MRCP, MSc (above), trial principal investigator from Queen Elizabeth Hospital Birmingham (QEHB) involved in an NHS program to develop personalized cancer vaccines, told the BBC. “My hope is this will become the standard of care. It makes sense that we can have something that can help patients reduce their risk of cancer recurrence.” These clinical trials could lead to new clinical laboratory screening tests for cancer vaccines. (Photo copyright: Queen Elizabeth Hospital Birmingham.)
Seven-Minute Cancer Treatment Injection
NHS England has also begun treating eligible cancer patients with under-the-skin injections of atezolizumab, an immunotherapy marketed under the brand name Tecentriq, Reuters reported. The drug is usually delivered intravenously, a procedure that can take 30 to 60 minutes. Injecting the drug takes just seven minutes, Reuters noted, saving time for patients and cancer teams.
The drug is designed to stimulate the patient’s immune system to attack cancer cells, including breast, lung, liver, and bladder cancers.
AI Advances in India
One WEF component—the Center for the Fourth Industrial Revolution (C4IR)—aims to harness emerging technologies such as artificial intelligence (AI) and virtual reality. In India, the organization says the Center is seeking to accelerate use of AI-based risk profiling to “help screen for common cancers like breast cancer, leading to early diagnosis.”
Researchers are also exploring the use of AI to “analyze X-rays to identify cancers in places where imaging experts might not be available.”
Using AI to Assess Lung Cancer Risk
Early-stage lung cancer is “notoriously hard to detect,” WEF observed. To help meet this challenge, researchers at Massachusetts Institute of Technology (MIT) developed an AI model known as Sybil that analyzes low-dose computed tomography scans to predict a patient’s risk of getting the disease within the next six years. It does so without a radiologist’s intervention, according to a press release.
Using Genomics to Identify Cancer-Causing Mutations
In what has been described as the “largest study of whole genome sequencing data,” researchers at the University of Cambridge in the UK announced they have discovered a “treasure trove” of information about possible causes of cancer.
Using data from England’s 100,000 Genomes Project, the researchers analyzed the whole genome sequences of 12,000 NHS cancer patients.
This allowed them “to detect patterns in the DNA of cancer, known as ‘mutational signatures,’ that provide clues about whether a patient has had a past exposure to environmental causes of cancer such as smoking or UV light, or has internal, cellular malfunctions,” according to a press release.
The researchers also identified 58 new mutational signatures, “suggesting that there are additional causes of cancer that we don’t yet fully understand,” the press release states.
The study appeared in April 2022 in the journal Science.
Validation of CAR-T-Cell Therapy
CAR-T-cell therapy “involves removing and genetically altering immune cells, called T cells, from cancer patients,” WEF explained. “The altered cells then produce proteins called chimeric antigen receptors (CARs), which can recognize and destroy cancer cells.”
The therapy appeared to receive validation in 2022 when researchers at the University of Pennsylvania published an article in the journal Nature noting that two early recipients of the treatment were still in remission after 12 years.
However, the US Food and Drug Administration (FDA) announced in 2023 that it was investigating reports of T-cell malignancies, including lymphoma, in patients who had received the treatment.
WEF observed that “the jury is still out as to whether the therapy is to blame but, as a precaution, the drug packaging now carries a warning.”
Breast Cancer Drug Repurposed for Prevention
England’s NHS announced in 2023 that anastrozole, a breast cancer drug, will be available to post-menopausal women to help reduce their risk of developing the disease.
“Around 289,000 women at moderate or high risk of breast cancer could be eligible for the drug, and while not all will choose to take it, it is estimated that if 25% do, around 2,000 cases of breast cancer could potentially be prevented in England, while saving the NHS around £15 million in treatment costs,” the NHS stated.
The tablet, which is off patent, has been used for many years to treat breast cancer, the NHS added. Anastrozole blocks the body’s production of the enzyme aromatase, reducing levels of the hormone estrogen.
Big Advance in Treating Cervical Cancer
In October 2024, researchers announced results from a large clinical trial demonstrating that a new approach to treating cervical cancer—one that uses currently available therapies—can reduce the risk of death by 40% and the risk of relapsing by 36%.
“This is the biggest improvement in outcome in this disease in over 20 years,” said Mary McCormack, PhD, clinical oncologist at the University College London and lead investigator in the trial.
The scientists published their findings in The Lancet.
Pathologists and clinical lab managers will want to keep track of these 12 breakthrough advancements in the diagnosis and treatment of cancer highlighted by the WEF. They will likely lead to new screening tests for the disease and could save many lives.
List also includes precision oncology, liquid biopsies, and early diagnosis of pancreatic cancer
Pathologists and clinical laboratory managers will be interested to learn that in a recently updated article the World Economic Forum (WEF) identified a dozen important recent breakthroughs in the ongoing fight to defeat cancer, including some related to pathology and clinical laboratory diagnostics.
The article noted that approximately 10 million people die each year from cancer. “Death rates from cancer were falling before the pandemic,” the authors wrote. “But COVID-19 caused a big backlog in diagnosis and treatment.”
The Swiss-based non-profit is best known for its annual meeting of corporate and government leaders in Davos, Switzerland. Healthcare is one of 10 WEF “centers” focusing on specific global issues.
Here are four advances identified by WEF that should be of particular interest to clinical laboratory leaders. The remaining advances will be covered in part two of this ebrief on Wednesday.
“Our study represents a major leap in cancer screening, combining the precision of protein-based biomarkers with the efficiency of sex-specific analysis,” said Novelna founder and CEO Ashkan Afshin, MD, ScD (above), in a company press release. “We’re not only looking at a more effective way of detecting cancer early but also at a cost-effective solution that can be implemented on a large scale.” The 12 breakthroughs listed in the World Economic Forum’s updated article will likely lead to new clinical laboratory screening tests for multiple types of cancer. (Photo copyright: Novelna.)
Novelna’s Early-Stage Cancer Test
Novelna, a biotech startup in Palo Alto, Calif., says it has developed a clinical laboratory blood test that can detect 18 early-stage cancers, including brain, breast, cervical, colorectal, lung, pancreatic, and uterine cancers, according to a press release.
In a small “proof of concept” study, scientists at the company reported that the test identified 93% of stage 1 cancers among men with 99% specificity and 90% sensitivity. Among women, the test identified 84% of stage 1 cancers with 85% sensitivity and 99% specificity.
The researchers collected plasma samples from 440 individuals diagnosed with cancers and measured more than 3,000 proteins. They identified 10 proteins in men and 10 in women that correlated highly with early-stage cancers.
“By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate,” states a BMJ Oncology press release.
The company says the test can be manufactured for less than $100.
“While further validation in larger population cohorts is necessary, we anticipate that our test will pave the way for more efficient, accurate, and accessible cancer screening,” said Novelna founder and CEO Ashkan Afshin, MD, ScD, in the company press release.
Precision Oncology
According to the National Institutes of Health’s “Promise of Precision Medicine” web page, “Researchers are now identifying the molecular fingerprints of various cancers and using them to divide cancer’s once-broad categories into far more precise types and subtypes. They are also discovering that cancers that develop in totally different parts of the body can sometimes, on a molecular level, have a lot in common. From this new perspective emerges an exciting era in cancer research called precision oncology, in which doctors are choosing treatments based on the DNA signature of an individual patient’s tumor.”
“These advanced sequencing technologies not only extend lifespans and improve cure rates for cancer patients through application to early screening; in the field of cancer diagnosis and monitoring they can also assist in the formulation of personalized clinical diagnostics and treatment plans, as well as allow doctors to accurately relocate the follow-up development of cancer patients after the primary treatment,” Wang wrote.
Based in China, Genetron Health describes itself as a “leading precision oncology platform company” with products and services related to cancer screening, diagnosis, and monitoring.
Liquid and Synthetic Biopsies
Liquid biopsies, in which blood or urine samples are analyzed for presence of biomarkers, provide an “easier and less invasive” alternative to conventional surgical biopsies for cancer diagnosis, the WEF article notes.
These tests allow clinicians to “pin down the disease subtype, identify the appropriate treatment and closely track patient response, adjusting course, if necessary, as each case requires—precision medicine in action,” wrote Merck Group CEO Belén Garijo, MD, in an earlier WEF commentary.
The WEF article also highlighted “synthetic biopsy” technology developed by Earli, Inc., a company based in Redwood City, Calif.
As explained in a Wired story, “Earli’s approach essentially forces the cancer to reveal itself. Bioengineered DNA is injected into the body. When it enters cancer cells, it forces them to produce a synthetic biomarker not normally found in humans.”
The biomarker can be detected in blood or breath tests, Wired noted. A radioactive tracer is used to determine the cancer’s location in the body.
“Pancreatic cancer is one of the deadliest cancers,” the WEF article notes. “It is rarely diagnosed before it starts to spread and has a survival rate of less than 5% over five years.”
The test is based on a technology known as high-conductance dielectrophoresis (DEP), according to a UC San Diego press release. “It detects extracellular vesicles (EVs), which contain tumor proteins that are released into circulation by cancer cells as part of a poorly understood intercellular communication network,” the press release states. “Artificial intelligence-enabled protein marker analysis is then used to predict the likelihood of malignancy.”
The test detected 95.5% of stage 1 pancreatic cancers, 74.4% of stage 1 ovarian cancers, and 73.1% of pathologic stage 1A lethally aggressive serous ovarian adenocarcinomas, they wrote.
“These results are five times more accurate in detecting early-stage cancer than current liquid biopsy multi-cancer detection tests,” said co-senior author Scott M. Lippman, MD.
Look to Dark Daily’s ebrief on Wednesday for the remainder of breakthroughs the World Economic Forum identifies as top advancements in the fight to defeat cancer.
Findings could lead to new clinical laboratory cancer screening tests for BRCA1 and BRCA2 among specific population regions
Descendants of a remote Scottish island are much more likely to carry a cancer-causing BRCA2 gene than the rest of the UK. That’s according to a study conducted by the University of Edinburgh in Scotland. For pathologists and clinical laboratory managers, the study’s findings demonstrate how ongoing research into the genetic makeup of subpopulations will find groups that have higher risk for specific health conditions than the general population. Thus, diagnosticians can pay closer attention to screening these groups to achieve early diagnosis and intervention.
“The findings follow earlier research from the Viking Genes study that found a cancer-causing variant in the related BRCA1 gene, common among people from Orkney [a group of islands off Scotland’s northern coast],” noted a University of Edinburgh news release.
In their latest research, the genetic scientists discovered that the BRCA2 gene can be found in one in every 40 people with heritage from the island of Whalsay in Scotland’s Shetland island group. This gene is one of the most common genes that can be linked to breast cancer and ovarian cancer in women and breast and prostate cancer in men.
Those who inherit the BRCA2 gene have a significantly higher risk of developing certain cancers than the general population. For example, according to the National Cancer Institute, more than 60% of women who inherit the gene will develop breast cancer in their lifetimes.
The volunteers in the Viking Genes study have a risk of having a BRCA2 gene that is 130 times higher than the general UK population. According to the BBC, geneticists believe the gene can be traced back to one family from the island of Whalsay before 1750.
“It is very important to understand that just two gene changes account for more than 90% of the inherited cancer risk from BRCA variants in Orkney and Shetland. This is in stark contrast to the situation in the general UK population, where 369 variants would need to be tested to account for the same proportion of cancer risk from BRCA genes. Any future screening program for the Northern Isles should therefore be very cost-effective,” said James Wilson, DPhil, FRCPE (above), Professor of Human Genetics at University of Edinburgh and leader of the study, in a news release. Clinical laboratories in the UK will be involved in those screenings. (Photo copyright: Scottish Genomes Partnership.)
Early Diagnosis Brings Hope to Families
The UK’s National Health Service (NHS) offers genetic testing to relatives of people with a known BRCA variant. Individuals with at least one Whalsay grandparent, and who have a close family history of breast, ovarian, or prostate cancer, can also request NHS testing.
As the BBC reported, University of Edinburgh’s discovery has given families answers and hope for the future. Individuals who fit the criteria for being at risk of inheriting the BRCA gene can narrow their testing and work more specifically on preventative measures with their doctors.
Christine Glaser, a woman from Lerwick in Shetland, learned she carried the BRCA gene after participating in the study. Though the Viking genes research took place nearly a decade ago, scientific understanding of genes has improved allowing geneticists to draw new conclusions from previous studies.
Although Glaser lost her sister to ovarian cancer, she and her family were unaware of their heightened genetic risk.
“I got offered preventative measures so I could get my ovaries removed and I could get a mastectomy. So, that’s what I did … when I got my ovaries removed, they checked them and there was no cancer, but then I had a mammogram and they found cancer,” she told the BBC. Glaser’s cancer was successfully treated thanks to early detection.
Closing Gap in Genetic Testing
“This BRCA2 variant in Whalsay I think arose prior to 1750. This is why these things become so common in given places because many people descend from a couple quite far back in the past, and if they have a cancer variant, then a significant number of people today—five or even 10 generations later—will have it. This is true everywhere in Scotland, it’s just magnified in these small places,” said James Wilson, DPhil, FRCPE, Professor of Human Genetics at University of Edinburgh, who led the study on Viking genes that found individuals with familial ties to two small Scottish communities may be at a higher risk of having a cancer-causing gene.
Wilson hopes to see testing for these genetic abnormalities become more common for these at-risk communities.
“The Ashkenazi Jewish community have BRCA1 and BRCA2 variants that also have a frequency of about one in 40,” he told the BBC. “The Ashkenazi Jewish population in England are able to take part in genetic testing for these genes but that’s not yet the case in Scotland.”
The findings of the most recent University of Edinburgh genetic study are very new. Future developments and offerings from the NHS may be influenced by the results.
Deeper understanding about the genetic make-up of certain population subgroups could lead to new genetic personalized medicine and preventative testing for those at risk of hereditary cancer. In turn, it could also encourage individuals to seek preventative care earlier. Thus, pathologists and clinical laboratory managers should keep an eye on these developments and be prepared to work with geneticists who may develop new screening methods for BRCA1 and BRCA2.
Although it is a non-specific procedure that does not identify specific health conditions, it could lead to new biomarkers that clinical laboratories could use for predictive healthcare
Researchers from the Mayo Clinic recently used artificial intelligence (AI) to develop a predictive computational tool that analyzes an individual’s gut microbiome to identify how a person may experience improvement or deterioration in health.
Dubbed the Gut Microbiome Wellness Index 2 (GMWI2), Mayo’s new tool does not identify the presence of specific health conditions but can detect even minor changes in overall gut health.
Built on an earlier prototype, GMWI2 “demonstrated at least 80% accuracy in differentiating healthy individuals from those with any disease,” according to a Mayo news release. “The researchers used bioinformatics and machine learning methods to analyze gut microbiome profiles in stool samples gathered from 54 published studies spanning 26 countries and six continents. This approach produced a diverse and comprehensive dataset.”
“Our tool is not intended to diagnose specific diseases but rather to serve as a proactive health indicator,” said senior study author Jaeyun Sung, PhD (above), a computational biologist at the Mayo Clinic Center for Individualized Medicine: Microbiomics Program in the news release ease. “By identifying adverse changes in gut health before serious symptoms arise, the tool could potentially inform dietary or lifestyle modifications to prevent mild issues from escalating into more severe health conditions, or prompt further diagnostic testing.” For microbiologists and clinical laboratory managers, this area of new knowledge about the human microbiome may lead to multiplex diagnostic assays. (Photo copyright: Mayo Clinic.)
Connecting Specific Diseases with Gut Microbiome
Gut bacteria that resides in the gastrointestinal tract consists of trillions of microbes that help regulate various bodily functions and may provide insights regarding the overall health of an individual. An imbalance in the gut microbiome is associated with an assortment of illnesses and chronic diseases, including cardiovascular issues, digestive problems, and some cancers and autoimmune diseases.
To develop GMWI2, the Mayo scientists provided the machine-learning algorithm with data on microbes found in stool samples from approximately 8,000 people collected from 54 published studies. They looked for the presence of 11 diseases, including colorectal cancer and inflammatory bowel disease (IBS). About 5,500 of the subjects had been previously diagnosed with one of the 11 diseases, and the remaining people did not have a diagnosis of the conditions.
The scientists then tested the efficacy of GMWI2 on an additional 1,140 stool samples from individuals who were diagnosed with conditions such as pancreatic cancer and Parkinson’s disease, compared with those who did not have those illnesses.
The algorithm gives subjects a score between -6 and +6. People with a higher GMWI2 score have a healthier microbiome that more closely resembles individuals who do not have certain diseases.
Likewise, a low GMWI2 score suggests the individual has a gut microbiome that is similar to those who have specific illnesses.
Highly Accurate Results
According to their study, the researchers determined that “GMWI2 achieves a cross-validation balanced accuracy of 80% in distinguishing healthy (no disease) from non-healthy (diseased) individuals and surpasses 90% accuracy for samples with higher confidence,” they wrote in Nature Communications.
Launched in 2020, the original GMWI (Gut Microbiome Wellness Index) was trained on a much smaller number of samples but still showed similar results.
The researchers tested the enhanced GMWI2 algorithm across various clinical schemes to determine if the results were similar. These scenarios included individuals who had previous fecal microbiota transplants and people who had made dietary changes or who had exposure to antibiotics. They found that their improved tool detected changes in gut health in those scenarios as well.
“By being able to answer whether a person’s gut is healthy or trending toward a diseased state, we ultimately aim to empower individuals to take proactive steps in managing their own health,” Sung said in the news release.
The Mayo Clinic team is developing the next version of their tool, which will be known as the Gut Microbiome Wellness Index 3. They plan to train it on at least 12,000 stool samples and use more sophisticated algorithms to decipher the data.
More research and studies are needed to determine the overall usefulness of Mayo’s Gut Microbiome Wellness Index and its marketability. Here is a world-class health institution disclosing a pathway/tool that analyzes the human microbiome to identify how an individual may be experiencing either an improvement in health or a deterioration in health.
The developers believe it will eventually help physicians determine how patients’ conditions are improving or worsening by comparing the patients’ microbiomes to the profiles of other healthy and unhealthy microbiomes. As this happens, it would create a new opportunity for clinical laboratories to perform the studies on the microbiomes of patients being assayed in this way by their physicians.
Though the cost of clinical laboratory testing is not highlighted in KFF’s annual survey, it is a component in how much employers pay for healthcare plans for their employees
Employers now pay higher health insurance premiums than ever for family coverage. However, because of the current tight labor market, they are generally absorbing much of that increase rather than passing the higher costs on to their workers. That’s one key takeaway from KFF’s 26th annual Employer Health Benefits Survey, which the non-profit published on Oct. 9, 2024. While the report does not comment specifically about the cost of clinical laboratory testing or genetic testing and how they may contribute to rising insurance costs, it stands to reason they are part of growing healthcare costs for corporate health benefits.
The KFF survey found that premiums for family coverage increased 7% in 2024, reaching an average of $25,572. That follows a 7% increase in 2023. “Over the past five years—a period of high inflation (23%) and wage growth (28%)—the cumulative increase in premiums has been similar (24%),” KFF stated in a press release.
However, the amount paid by workers has gone up by less than $300 since 2019. It now stands at an average of $6,296, a total increase of 5% over five years. On average, workers covered 25% of family premium costs in 2024, down from 29% in 2023. Workers with single coverage paid an average of $1,368—16% of the annual premium cost—compared with 17% in 2023.
“Employers are shelling out the equivalent of buying an economy car for every worker every year to pay for family coverage,” KFF President and CEO Drew Altman, PhD (above), said in a press release. “In the tight labor market in recent years, they have not been able to continue offloading costs onto workers who are already struggling with healthcare bills.” Rising costs of clinical laboratory testing is always part of the mix contributing to increased worker insurance premiums for employers. (Photo copyright: KFF.)
HDHP/SO plans, as defined by KFF, “have a deductible of at least $1,000 for single coverage and $2,000 for family coverage and are offered with an HRA [Health Reimbursement Arrangement] or are HSA [health savings account]-qualified.” Point-of-service plans “have lower cost sharing for in-network provider services and do not require a primary care gatekeeper to screen for specialist and hospital visits,” the report states.
Cost Sharing via Deductibles
Average deductible amounts—which KFF identified as another form of cost-sharing—varied depending on the type of plan, employer size, and whether the worker had family or single coverage.
For workers with single coverage, average deductibles across all plan types rose from $1,655 in 2019 to $1,787 in 2024, a total five-year increase of about 8%. The average in 2023 was $1,735. These numbers were for in-network providers.
The report noted that some family plans calculate deductibles using an aggregate structure, “in which all family members’ out-of-pocket expenses count toward the deductible,” whereas others use a separate per-person structure. The report includes breakdowns of average deductibles across all types.
Who Offers the Best Benefits?
In general, the KFF report found that large companies—defined as those with 200 or more workers—tend to offer more generous health benefits than smaller ones. Virtually all large companies (98%) offered health benefits, while slightly more than half of small companies (53%) do so.
Among companies that do offer health benefits, the average deductible at a small firm was $2,575 compared to $1,538 at large firms. Among workers with family coverage, the average contribution toward overall premium costs was $7,947 (33%) at small firms compared to $5,697 (23%) at large firms. Among workers with single coverage, the numbers were $1,429 (16%) at small firms compared to $1,204 (14%) at large firms.
The report also found variations in overall premiums and health benefits across nine different industries. For example, healthcare firms paid the highest premiums for family coverage—an average of $26,864—followed by transportation/communications/utilities at $26,601. Companies in agriculture, mining, and construction paid the lowest premiums, an average of $22,654.
There were wide variations by industry in terms of how many firms offer any health benefits. Among state and local government entities, 83% offered health benefits, followed by transportation/communications/utilities (69%), manufacturing (65%), wholesale (62%), healthcare (58%), and finance (56%). Just 40% of retail businesses and 49% of agriculture/mining/construction businesses offered health benefits.
Health Screening Coverage
The KFF report did not include data about insurance coverage for clinical laboratory services. However, one section did address employer willingness to provide opportunities for health screening.
Among large businesses, 56% offered health risk assessments, in which individuals answer questions about their medical history, lifestyle, and other areas relevant to their health risks. A smaller number (44%) offer biometric screening, which “could include meeting a target body mass index (BMI) or cholesterol level, but not goals related to smoking,” the report said. Only 9% of small businesses offered biometric screening, the report found.
KFF conducted its survey between January and July 2024 among a random selection of public and private employers with at least three workers. The survey excluded federal government entities but included state and local government. A total of 2,142 employers responded.
Inflation during this current administration definitely hit consumers in the health insurance premium pocketbook. At the same time providers raised their own prices making it more expensive for people with HDHPs to come up with the cash required by their annual deductible. While clinical laboratory and genetic testing are not highlighted in KFF’s survey, they certainly play a role in increasing costs to healthcare consumers and are worth considering.
New clinical laboratory test could replace conventional spinal tap for diagnosing neurodegenerative disease
In a proof-of-concept study, University of Pittsburgh (Pitt) scientists validated a clinical laboratory test that measures more than 100 different genetic sequences associated with Alzheimer’s disease. The Pitt researchers believe the new diagnostic platform could help clinicians “capture the multifaceted nature of Alzheimer’s pathology and streamline early disease diagnostics,” according to a news release.
Clinical laboratory blood tests that detect biomarkers such as phosphorylated tau protein (pTau) have emerged in studies as diagnostic possibilities for Alzheimer’s disease, which is traditionally diagnosed using a lumbar puncture (spinal tap) procedure.
In their paper, neuroscientist Thomas Karikari, PhD, Assistant Professor of Psychiatry at University of Pittsburgh, lead author of the study, and his research team acknowledged that progress has been made in detecting Alzheimer’s disease with blood-based biomarkers. However, they note that “two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction.”
The Pitt scientists believe the focus on so-called “classical Alzheimer’s blood biomarkers” limits exploration of neurodegenerative disease.
“Alzheimer’s disease should not be looked at through one single lens. Capturing aspects of Alzheimer’s pathology in a panel of clinically validated biomarkers would increase the likelihood of stopping the disease before any cognitive symptoms emerge,” said neuroscientist Thomas Karikari, PhD (above), Assistant Professor of Psychiatry, University of Pittsburgh, and lead author of the study in a news release. Should further studies prove Pitt’s research sound, clinical laboratories may have a replacement test for diagnosing neurodegenerative disease. (Photo copyright: University of Pittsburgh.)
On its website, Alamar Biosciences explains that the disease panel offers neurological researchers:
“Multiplexed analysis of 120 neuro-specific and inflammatory proteins from 10 µl of plasma or CSF (cerebrospinal fluid).
Detection of “critical biomarkers—including pTau-217, GFAP (glial fibrillary acidic protein), NEFL (neurofilament light polypeptide) and alpha-synuclein.”
The NULISAseq test works with “a proprietary sequential immunocomplex capture and release mechanism and the latest advances in next-generation sequencing,” according to the company.
Inside Precision Medicine noted that the Alamar Biosciences assay enabled Pitt scientists to detect:
Biomarkers (usually found in CSF) “correlating with patients’ amyloid positivity status and changes in amyloid burden over time,” and,
Biomarkers including “neuroinflammation, synaptic function, and vascular health, which had not previously been validated in blood samples.”
“The performance of the NULISA platform was independently validated against conventional assays for classic Alzheimer’s biomarkers for each sample. Biomarker profiles over two years were also compared with imaging-based measures of amyloid, tau, and neurodegeneration,” LabMedica reported.
Opportunity to Track Alzheimer’s
Karikari sees the diagnostic platform being used to track individuals’ blood biomarker changes over time.
In their Molecular Neurodegeneration paper, the Pitt researchers wrote, “These (results) were not limited to markers such as pTau217, p-Tau231, p-Tau181, and GFAP, the elevation of which have consistently shown strong associations with brain Aβ [amyloid beta] and/or tau load, but included novel protein targets that inform about the disease state of the individual in different pathological stages across the biological Alzheimer’s disease continuum.”
About seven million Americans are affected by Alzheimer’s disease, according to the Alzheimer’s Association, which estimated that figure will grow to 13 billion by 2050.
Further studies by Karikari may include larger samples and greater diversity among the people studied, Inside Precision Medicine noted.
“[Karikari’s] lab is developing a predictive model that correlates biomarker changes detected using NULISAseq with brain autopsy data and cognitive assessments collected over the course of several years. Their goal is to identify blood biomarkers that can help stage the disease and predict its progression, both for decision-making around clinical management and treatment plans,” the Pitt news release states.
The Pitt scientists have developed a multiplex test that works with 100 different genetic sequences associated with Alzheimer’s. Such advances in the understanding of the human genome are giving scientists the opportunity to combine newly identified gene sequences that have a role in specific disease states.
In turn, as further studies validate the value of these biomarkers for diagnosing disease and guiding treatment decisions, clinical laboratories will have new assays that deliver more value to referring physicians and their patients.
