With further study, this research may provide clinical laboratories with a new proteomic biomarker for dementia screenings that identifies risk more than 10 years before symptoms appear
Researchers at the University of Warwick in the UK and Fudan University in Shanghai, China, identified four protein biomarkers in blood that they say can predict dementia up to 15 years before diagnosis. They say these biomarkers may lead to clinical laboratory blood tests that offer alternatives to costly brain scans and lumbar punctures for diagnosis of dementia.
The scientists “used the largest cohort of blood proteomics and dementia to date,” according to a University of Warwick news release. This included taking blood from 52,645 “healthy” people without dementia who participated in the UK Biobank—a population-based study cohort, the new release noted.
“The proteomic biomarkers are [easy] to access and non-invasive, and they can substantially facilitate the application of large-scale population screening,” said neurovegetative disease specialist Jin-tai Yu, MD, PhD, a professor at Fudan University and co-author of the study, in the news release.
“The advent of proteomics offers an unprecedented opportunity to predict dementia onset,” the researchers wrote.
“This is a well-conducted study that adds to what we know about changes in blood that occur very early in diseases that cause dementia, which will be important for early diagnosis in the future,” said Tara Spires-Jones, PhD, in a post from the Science Media Center in the UK. “However,” she added, “it is important to note that these are still scientific research studies and that there are currently no blood tests available for routine use that can diagnose dementia with certainty.
“Based on this study, it does seem likely that blood tests will be developed that can predict risk for developing dementia over the next 10 years, although individuals at higher risk often have difficulty knowing how to respond,” Suzanne Schindler, MD, PhD (above), told Reuters. Schindler, an Associate Professor of Neurology at Washington University in St. Louis, was not involved in the research. Clinical laboratories may soon have a new blood test for dementia. (Photo copyright: VJDementia.)
Predicting Onset of Dementia with 90% Accuracy
The researchers analyzed 52,645 blood samples from the UK Biobank (UKBB). The samples were collected between 2006 and 2010 from healthy individuals who at that time were without dementia.
By March 2023, 1,417 of the study participants had developed Alzheimer’s disease or some other form of dementia. The researchers looked at 1,463 proteins and identified four that were present in high levels among those people:
“Individuals with higher GFAP levels were 2.32 times more likely to develop dementia,” the researchers wrote in Nature Aging. “Notably, GFAP and LTBP2 were highly specific for dementia prediction. GFAP and NEFL began to change at least 10 years before dementia diagnosis.”
When adding known risk factors such as age, sex, and genetics, the researchers said they could predict onset of dementia with 90% accuracy, according to the University of Warwick news release.
“Our findings strongly highlight GFAP as an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis, with implications for screening people at high risk for dementia and for early intervention,” the researchers wrote.
The news release also noted that smaller studies had already identified some of the proteins as potential biomarkers, “but this new research was much larger and conducted over several years.”
Further Validation Needed
Amanda Heslegrave, PhD, of the UK Dementia Research Institute, University College London described the UKBB as “an excellent resource” in the Science Media Center (SMC) post. However, she noted, it’s “a highly curated biobank and may not capture all populations that we need to know the risk for. The new biomarkers identified will need further validation before being used as screening tools.”
Another expert raised additional questions about the University of Warwick/Fudan University study in the SMC post.
“These results may help researchers understand the biological systems involved in the development of dementia,” said David Curtis, MD, PhD, of the UCL Genetics Institute at University College London. “However in my view the strengths of the reported associations are not really strong enough to say that these would form a useful test for predicting who will get dementia in the future.”
Conversely, Curtis pointed to other studies suggesting that phosphorylated tau (p-tau) proteins are better candidates for developing a simple blood test.
P-tau “provides a very good indicator of whether the pathological processes leading to Alzheimer’s disease are present in the brain,” he said. “When effective treatments for Alzheimer’s disease are developed it will be very helpful indeed to have simple blood tests—such as measuring phosphorylated tau—available in order to identify who could benefit.”
At least two blood tests based on the p-tau217 variant—from ALZpath and C2N—are currently available to US clinicians as laboratory developed tests (LDT).
The UK Biobank continues to be used by researchers both in the UK and abroad because of the full sets of data on large numbers of patients over many years. There are few other sources of such data elsewhere in the world. The UK Biobank is a large-scale biomedical database and research resource. It contains de-identified genetic, lifestyle and health information, and biological samples from 500,000 UK participants.
On its website, the UK Biobank states, “It is the most comprehensive and widely-used dataset of its kind and is globally accessible to approved researchers who are undertaking health-related research that is in the public interest, whether they are from academic, commercial, government or charitable settings.”
Thus, clinical laboratory managers and pathologists can expect a continuing stream of published studies that identify biomarkers associated with different health conditions and to see where the data used in these analyses came from the UK’s biobank.
Trifecta of forces at work that will affect the clinical laboratory and pathology industries have been described as a ‘perfect storm’ requiring lab and practice managers to be well informed
Digital pathology, artificial intelligence (AI) in healthcare, and the perfect storm of changing federal regulations, took centerstage at the 29th Executive War College on Diagnostics, Clinical Laboratory, and Pathology Management in New Orleans this week, where more than 1,000 clinical laboratory and pathology leaders convened over three days.
This was the largest number of people ever onsite for what has become the world’s largest event focused exclusively on lab management topics and solutions. Perhaps the highlight of the week was the federal Food and Drug Administration’s (FDA’s) announcement of its final rule on Laboratory Developed Tests (LDTs). Overall, the conference featured more than 120 speakers, many of them national thought leaders on the topic of clinical lab and pathology management. More than 65% of the audience onsite were executive level lab managers.
“The level of interest in the annual Executive War College is testimony to the ongoing need for dynamic, engaging, and highly relevant conference events,” said Robert Michel (above), Editor-in-Chief of Dark Daily and its sister publication The Dark Report, and founder of the Executive War College. “These in-person gatherings present great opportunities for clinical laboratory and pathology managers and leaders to network and speak with people they otherwise might not meet.” (Photo copyright: Dark Intelligence Group.)
Demonstrating Clinical Value
For those who missed the action onsite, the following is a synopsis of the highlights this week.
Lâle White, Executive Chair and CEO of XiFin, spoke about the future of clinical laboratory testing and the factors reshaping the industry. There are multiple dynamics impacting healthcare economics and outcomes—namely rising costs, decreasing reimbursements, and the move to a more consumer-focused healthcare. But it is up to labs, she said, to ensure their services are not simply viewed as a commodity.
“Laboratory diagnostics have the potential to change the economics of healthcare by really gaining efficiencies,” she noted. “And it’s up to labs to demonstrate clinical value by helping physicians manage two key diagnostic decision points—what tests to order, and what to do with the results.”
But even as labs find ways to increase the value offered to clinicians, there are other disruptive factors in play. Consumer-oriented tech companies such as Google, Apple, and Amazon are democratizing access to patient data in unforeseen ways, and Medicare Advantage plans are changing the way claims are processed and paid.
Clinical labs are fundamental components of the public health infrastructure. So, the CDC plans on focusing on delivering high-quality laboratory science, supported by reliable diagnostics and informatics for disease outbreaks and exposures, and engaging with public and private sector partners.
The history of MolDX and Z-Codes were the topics discussed by Gabriel Bien-Willner, MD, PhD, Chief Medical Officer for healthcare claims and transaction processing company Palmetto GBA. Molecular testing is highly complex, and the lack of well-defined billing codes and standardization makes it difficult to know if a given test is reasonable and necessary.
Z-Codes were established to clarify what molecular testing was performed—and why—prompting payers to require both Z-Codes and Current Procedural Terminology (CPT) codes when processing molecular test claims. Medicare’s MolDX program further streamlines the claims process by utilizing expertise in the molecular diagnostics space to help payers develop coverage policies and reimbursement for these tests.
FDA Final Rule on LDT Regulation
Timothy Stenzel, MD, PhD, CEO of Grey Haven Consulting and former director of the FDA’s Office of In Vitro Diagnostics reviewed the latest updates from the FDA’s Final Rule on LDT (laboratory developed test) regulation. Prior to the FDA releasing its final rule, some experts suggested that the new regulations could result in up to 90% of labs discontinuing their LDT programs, impacting innovation, and patient care.
However, the final rule on LDTs is very different from the original proposed rule which created controversy. The final rule actually lowers the regulatory burden to the point that some labs may not have to submit their LDTs at all. The FDA is reviewing dozens of multi-cancer detection assays, some of which have launched clinically as LDTs. The agency is likely to approve those that accurately detect cancers for which there is no formal screening program.
Stenzel explained the FDA’s plan to down-classify most in vitro diagnostic tests, changing them from Class III to Class II, and exempting more than 1,000 assays from FDA review. He also discussed the highlights of the Quality Management System Regulation (QMSR). Launched in January, the QMSR bought FDA requirements in line with ISO 13485, making compliance easier for medical device manufacturers and test developers working internationally.
Looming Perfect Storm of Regulatory Changes
To close out Day 1, Michel took to the stage again with a warning to clinical laboratories about the looming “Perfect Storm” trifecta—the final FDA ruling on LDTs, Z-Code requirements for genetic testing, and updates to CLIA ’92 that could result in patient data being considered a specimen.
Laboratory leaders must think strategically if their labs are to survive the fallout, because the financial stress felt by labs in recent years will only be exacerbated by macroeconomic trends such as:
Staff shortages,
Rising costs,
Decreasing and delayed reimbursements, and
Tightening supply chains.
Lab administrators looking for ways to remain profitable and prosperous should look beyond the transactional Clinical Lab 1.0 fee-for-service model and adopt Clinical Lab 2.0, which embraces HEDIS (Healthcare Effectiveness Data and Information Set) scores and STAR ratings to offer more value to Medicare Advantage and other payers.
Wednesday’s General Session agenda was packed with information about the rise of artificial intelligence, big data, and precision medicine in healthcare. Taking centerstage on the program’s final day was Michael Simpson, President and CEO of Clinisys. Simpson gave a global perspective on healthcare data as the new driver of innovation in diagnostics and patient care.
“The timing of EWC with the release of this policy couldn’t be better,” CEO and founder of Momentum ConsultingValerie Palmieri told Dark Daily in an interview at Monday night’s opening reception. “It’s a great conference to not only catch up with colleagues but really hear and have those difficult discussions about where we are today, where we’re going, and where we need to be.”
Final LDT rule ‘radically’ different than draft
Tim Stenzel, MD, PhD, former director of the FDA’s Office of In Vitro Diagnostics called the finalized rule “radically different” from the proposed rule. In some ways it is less complex: “The bar is lower,” he said, noting that he was voicing his personal views and not those of the federal agency. “I was convinced that there would be lawsuits, but I’m now not sure if that’s advisable.”
Still, laboratory teams will have to parse the more than 500-page document to determine how the final rule relates to their specific circumstances. After that, it won’t be as challenging, Stenzel said.
His advice: First, read the rule. Second, reach out to FDA for help—he’s sure, he said, that the office is geared up to respond to a “ton of questions” about the implications for individual labs and are standing by to answer emails from labs. And, he added in a discussion session, emailing the agency is free.
The final rule will be in force 60 days after it’s published. Stenzel provided a timeline for some of the milestones:
1 Year: Comply with MD(AE) reporting and reporting of corrections and removals.
2 Years: Comply with labeling, registration and listing, and investigational use requirements.
3 Years: QS records and, in some cases, design controls and purchasing controls.
3.5 Years: Comply with high risk (class III) premarket review requirements.
4 Years: Comply with moderate and low-risk premarket review requirements.
Executive Chair and CEO of XiFin, Inc.Lâle White welcomed the audience with a morning keynote entitled “Big Changes in Healthcare” on new regulations and diagnostics players poised to reshape lab testing.
The diagnostics business is in constant flux, she noted, from payer requirements to greater regulatory and compliance burdens on labs. Other factors include the growing senior population and increasingly complex health conditions, rising costs throughout the healthcare ecosystem, falling funding and reimbursement, and staffing shortages.
As for the economic challenges, consumers are increasingly making decisions based on cost, convenience and quality. The population is shifting to Medicare advantage, which is more cost effective. But changes to the star ratings system will mean lower pay for payer organizations. Those companies will, in turn, mitigate their losses by making changes to pre-authorizations and tightening denials, even for clean claims.
Still, White said, more money isn’t the answer.
White urged the audience to use technology, including artificial intelligence and advances in genetic testing, to manage these and other industry changes.
“We need to optimize the tests we order,” she said. “And if we did that, lab diagnostics really has the potential to change the economics of health and improve outcomes.”
The FDA, Stenzel added, is “very interested” in stimulating innovation, building on the laboratory industry’s success in responding swiftly to the COVID pandemic and outbreaks of Monkey Pox, for example.
He shared lessons learned from recent public health emergencies, talked about CDC’s efforts to engage with clinical labs to improve future public health readiness and response and provided an overview of the CDC’s first laboratory-specific center.
“Laboratories are fundamental to public health,” he said. The industry is on the “front lines” when it comes to identifying threats, responding to them, and preparing for future responses.
Robert Michel, Editor-in-Chief of The Dark Report wrapped up the day’s regulatory discussions with a general session on the “regulatory trifecta” that includes the LDT final rule, CLIA regulations, and private payers’ policies for genetic claims.
In a follow-up story, investigative news team in Boston sends a reporter’s cheek swab sample to the same pet DNA testing lab: report states the reporter is part Malamute, Shar Pei, and Labrador Retriever
One pet DNA testing company returned results from human cheek swabs showing two different people were in fact part dog. The resulting local reporting calls into question the accuracy of DNA testing of our beloved furry friends and may impact the trust people have in clinical laboratory genetic testing as well.
Pet DNA analysis is nearly as popular as human DNA analysis. The market is expected to exceed $700 million by the end of the decade, according to Zion Market Research. But are customers getting their money’s worth? One CBS news station in Boston decided to find out.
Last year, the WBZ I-Team, the investigative part of a CBS News station in Boston, looked into the accuracy of pet DNA testing. They reported on a pet owner who questioned the DNA test results she received for her German Shepard. The report indicated that her dog had DNA from more than 10 breeds, besides German Shepard.
During their research, the WBZ investigative reporters learned that pet owners order these tests to reveal what one pet DNA testing company described as understanding “your dog’s unique appearance, behavior, and health.”
“So, the WBZ-TV I-Team came with more tests from different companies to compare. All came back with some German Shepherd, but the percentages ranged from 65% to just 29%. Aside from that, the three companies showed a puzzling hodgepodge of other breeds. One included Great Pyrenees, another came back with Siberian Husky, another listed Korean Jindo, and the list goes on,” WBZ News reported.
The owner of the German Shepard then sent two swab samples from her own cheeks to one of the pet DNA testing companies. The test results indicated that she was 40% Border Collie, 32% Cane Corso, and 28% Bulldog.
The company that performed that DNA testing—DNA My Dog—insisted to the WBZ I-Team that one of the pet owner’s cheek samples contained dog DNA, WBZ News reported.
“The second sample did in fact yield canine DNA. … The results provided would not be possible on a human sample,” Jessica Barnett, Director of Service Operations, DNA My Dog, told WBZ News.
This must have come as a shock to the pet owner, who is probably sure she is not part dog.
“I think that is a red flag for sure,” Lisa Moses, VMD (above), a veterinarian and bioethicist with Harvard Medical School, told WBZ News. “A company should know if they’ve in any basic way analyzed a dog’s DNA, that that is not a dog,” she said. One wonders what might happen if a dog’s DNA was secretly sent to a clinical laboratory performing human genetic testing. What might the results be? (Photo copyright: Harvard Medical School.)
Two Times is the Charm
To continue its investigation into this odd occurrence, the WBZ I-Team decided to repeat the test this year. They sent a cheek saliva sample from one of their own reporters to three different dog DNA testing companies.
According to the I-Team report, one company, Orivet, said the sample “failed to provide the data necessary to perform breed ID analysis. Another company, Wisdom Panel stated the sample “didn’t provide enough DNA to produce a reliable result.”
However, DNA My Dog once again reported that the human sample belonged to a canine. This time the company’s test reported that the DNA sample was 40% Alaskan Malamute, 35% Shar Pei, and 25% Labrador Retriever.
DNA My Dog did not respond to WBZ I-Team’s attempt to contact them for a comment, WBZ News reported.
Wild West of DNA Testing
“I personally do have concerns about the fact that, from a consumer standpoint, you don’t always know what you’re getting when you work with those companies,” said geneticist Elinor Karlsson, PhD, Director of the Vertebrate Genomics Group at the Broad Institute of MIT and Harvard, told WBZ News. “There’s not a lot of rules in this space.”
Karlsson is also founder and Chief Scientist at Darwin’s Ark, a nonprofit organization that combines dog genetics and behavior to advance the understanding of complex canine diseases. People participating in the initiative contribute data about their dogs to an open source database, which is then shared with researchers around the globe. To date, more than 44,000 dogs have been registered with the project.
She hopes that reports like the one from the WBZ I-Team will not dissuade interest in pet genetics, as the science does have significant value when performed correctly.
“We might be able to figure out which dogs are at risk of getting cancer, and screen them more often and be able to diagnose it earlier,” Karlsson said. “We might be able to develop new treatments for that cancer.”
“There isn’t necessarily a gold standard answer for what your dog is,” veterinarian and bioethicist Lisa Moses, VMD, co-director of the Capstone Program for the Master of Science in Bioethics Program at Harvard Medical School, told WBZ News. “A breed is something that we’ve decided, which is based upon essentially the way a dog looks. But that doesn’t necessarily mean that we’re going to know what their genes look like.”
DNA My Dog Awarded ‘Best Budget Dog DNA Test’
In February, US News and World Report published an article rating the best dog DNA tests of 2024. The magazine ranked the DNA My Dog Essential Breed ID Test as the “best budget dog DNA test on the market.” The test sells for $79.99. According to the company’s website, a simple cheek swab yields:
A complete breed breakdown,
Genetic health concerns,
Unique personality traits, and
Bonding tips for dogs and their owners.
“I worry about people making medical decisions … based on one of these tests,” Moses told WBZ News, which added that, “She and some of her colleagues have called on lawmakers to set standards and regulations for pet DNA labs, and to require them to share their databases with each other, for more consistent results.”
The investigation into pet DNA testing by the television news reporters in Boston is a reminder to clinical lab managers and pathologists that DNA testing can be problematic in many ways. Also, when consumers read news stories like this one about inaccurate canine DNA testing, it can cause them to question the accuracy of other types of DNA testing.
New non-invasive test could replace traditional painful spinal taps and clinical laboratory fluid analysis for diagnosis of Parkinson’s disease
Scientists at AXIM Biotechnologies of San Diego have added another specimen that can be collected non-invasively for rapid, point-of-care clinical laboratory testing. This time it is tears, and the diagnostic test is for Parkinson’s disease (PD).
The new assay measures abnormal alpha-synuclein (a-synuclein), a protein that is a biomarker for Parkinson’s, according to an AXIM news release which also said the test is the first rapid test for PD.
“The revolutionary nature of AXIM’s new test is that it is non-invasive, inexpensive, and it can be performed at a point of care. It does not require a lumbar puncture, freezing, or sending samples to a lab. AXIM’s assay uses a tiny tear drop versus a spinal tap to collect the fluid sample and the test can be run at a doctor’s office with quantitative results delivered from a reader in less than 10 minutes,” the news release notes.
“Furthermore, emerging evidence shows that a-synuclein assays have the potential to differentiate people with PD from healthy controls, enabling the potential for early identification of at-risk groups,” the news release continues. “These findings suggest a crucial role for a-synuclein in therapeutic development, both in identifying pathologically defined subgroups of people with Parkinson’s disease and establishing biomarker-defined at-risk cohorts.”
This is just the latest example of a disease biomarker that can be collected noninvasively. Other such biomarkers Dark Daily has covered include:
“With this new assay, AXIM has immediately become a stakeholder in the Parkinson’s disease community, and through this breakthrough, we are making possible new paradigms for better clinical care, including earlier screening and diagnosis, targeted treatments, and faster, cheaper drug development,” said John Huemoeller, CEO, AXIM (above), in a news release. Patients benefit from non-invasive clinical laboratory testing. (Photo copyright: AXIM Biotechnologies.)
Fast POC Test versus Schirmer Strip
AXIM said it moved forward with its novel a-synuclein test propelled by earlier tear-related research that found “a-synuclein in its aggregated form can be detected in tears,” Inside Precision Medicine reported.
But that research used what AXIM called the “outdated” Schirmer Strip method to collect tears. The technique involves freezing tear samples at -80 degrees Celsius (-112 Fahrenheit), then sending them to a clinical laboratory for centrifugation for 30 minutes; quantifying tear protein content with a bicinchoninic acid assay, and detecting a-synuclein using a plate reader, AXIM explained.
Alternatively, AXIM says its new test may be performed in doctors’ offices and offers “quantitative results delivered from a reader in less than 10 minutes.”
“Our proven expertise in developing tear-based diagnostic tests has led to the development of this test in record speed, and I’m extremely proud of our scientific team for their ability to expand our science to focus on such an important focus area as Parkinson’s,” said John Huemoeller, CEO, AXIM in the news release.
“This is just the beginning for AXIM in this arena,” he added. “But I am convinced when pharmaceutical companies, foundations, and neurologists see how our solution can better help diagnose Parkinson’s disease in such an expedited and affordable way, we will be at the forefront of PD research, enabling both researchers and clinicians a brand-new tool in the fight against PD.”
One of those tests was “a lateral flow diagnostic for point-of-care use that measures the level of lactoferrin proteins in tear fluid, which work to protect the surface of the eye. … Axim said that low lactoferrin levels have also been linked to Parkinson’s disease and that the assay can be used alongside its alpha-synuclein test,” Fierce Biotech noted.
“It made sense to try and look at the proteinaceous [consisting of or containing protein] constituents of tear fluid,” Lew told Neurology Live. “Tear fluid is easy to collect. It’s noninvasive, inexpensive. It’s not like when you do a lumbar puncture, which is a much more involved ordeal. There’s risk of contamination with blood (saliva is dirty) issues with blood and collection. [Tear fluid analysis] is much safer and less expensive to do.”
In Biomarkers in Medicine, Lew et al noted why tears make good biomarkers for Parkinson’s disease, including “the interconnections between the ocular [eye] surface system and neurons affected in Parkinson’s disease.”
The researchers also highlighted “recent data on the identification of tear biomarkers including oligomeric α-synuclein, associated with neuronal degeneration in PD, in tears of PD patients” and discussed “possible sources for its release into tears.”
Future Clinical Laboratory Testing for Parkinson’s
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s. It affects nearly one million people in the US. About 1.2 million people may have it by 2030, according to the Parkinson’s Foundation.
Thus, an accurate, inexpensive, non-invasive diagnostic test that can be performed at the point of care, and which returns clinical laboratory test results in less than 10 minutes, will be a boon to physicians who treat PD patients worldwide.
Clinical laboratory managers and pathologists may want to follow AXIM’s future research to see when the diagnostic test may become available for clinical use.
Pathologists and clinical laboratories have an opportunity to help create newborn rWGS programs in their parent hospitals and health systems
Diagnosing disease in infants is particularly difficult using typical clinical laboratory testing and modalities. Thus, the use of rapid Whole Genome Sequencing (rWGS) is gaining acceptance when such a procedure is deemed “medically appropriate” based on the child’s symptoms.
In “Whole Genome Sequencing for Newborns Gains Favor,” Robert Michel, Editor-in-Chief of Dark Daily’s sister publication The Dark Report wrote, “Evidence is swiftly accumulating that use of rapid Whole Genome Sequencing for certain children in NICUs can enable diagnostic insights that guide effective interventions. Further, these pilot rWGS programs in children’s hospitals are showing a solid return on investment because of improved care. It is predicted that more hospitals may soon offer rWGS.”
Conducted at Tufts Medical Center in Boston, the researchers found that “Whole genome tests are nearly twice as good as narrower tests at unearthing genetic abnormalities that can cause disease in infants—the study found 49% of abnormalities, compared to 27% with more commonly used tests targeting particular types of genetic diseases,” the Associate Press reported.
The AP story follows the medical journey of a now 4-year-old who was diagnosed with a rare bleeding disorder. The nearly fatal condition was only caught because broad genetic testing found she suffered from factor XIII deficiency, a blood disorder characterized by the inability to clot properly.
“I’ve been doing clinical trials of babies for over 40 years,” neonatologist Jonathan Davis, MD (above), Chief, Division of Newborn Medicine at Tufts Children’s Hospital at Tufts Medical Center and Professor of Pediatrics, Tufts University School of Medicine, told the AP. “It’s not often that you can do something that you feel is going to really change the world and change clinical practice for everyone.” Clinical laboratories that work with oncologists to treat children suffering from cancer will understand Davis’ enthusiasm. (Photo copyright: Tufts Medicine.)
Incorporating Rapid Whole Genome Sequencing into Infant Care
Genetic diseases are responsible for 41% of infant deaths, according to a Rady Children’s Institute press release, which goes on to say the usage of rWGS may significantly improve the odds for infants born with genetic disorders.
“Broad use of genomic sequencing during the first year of life could have a much greater impact on infant mortality than was recognized hitherto,” said Stephen Kingsmore MD, President/CEO, Rady Children’s Institute for Genomic Medicine, which was one of the additional study sites for the Tufts Medicine researchers.
Genetic testing is already used to predict infant health outcomes, but the Tufts study highlights further developments that could improve the process. Prenatal genetic testing can be utilized both through carrier testing to determine any potential genetic red flags in the parents, and during prenatal screening and diagnostic testing of the fetus.
When an infant presents symptoms after birth, rWGS can then be implemented to cast a broad net to determine the best course of treatment.
According to ScienceDaily, the Tufts study found rWGS “to be nearly twice as effective as a targeted gene sequencing test at identifying abnormalities responsible for genetic disorders in newborns and infants.”
However, the rWGS tests took an average of six days to come back, whereas the targeted tests took only four days, ScienceDaily reported. Also, there is not full consensus on whether a certain gene abnormality is actually the cause of a specific genetic disorder.
“Many neonatologists and geneticists use genome sequencing panels, but it’s clear there are a variety of different approaches and a lack of consensus among geneticists on the causes of a specific patient’s medical disorder,” Jill Maron, MD, Vice Chair of Pediatric Research, Tufts Medical Center, and a co-principal investigator of the Tufts study, told Science Daily.
rWGS Costs versus Return on Investment
Some also question the upfront cost of genetic testing. It can be high, but it’s coming down and Maron stresses the importance of the tests.
“Genome sequencing can be costly, but in this targeted, at-risk population, it proves to be highly informative. We are supportive of ongoing efforts to see these tests covered by insurance,” she told ScienceDaily.
Each of the doctors associated with the Tufts study emphasized the importance of this testing and the good that can be done for this vulnerable group. The potential value to the children, they say, far outweighs the drawbacks of the testing.
“This study provides further evidence that genetic disorders are common among newborns and infants,” Kingsmore told ScienceDaily, “The findings strengthen support for early diagnosis by rapid genomic sequencing, allowing for the use of precision medicine to better care for this vulnerable patient population.”
For clinical laboratories, there is also good news about reimbursement for rWGS. In a story published last fall KFF Health News wrote, “Since 2021, eight state Medicaid programs have added rapid whole-genome sequencing to their coverage or will soon cover it, according to GeneDX, a provider of the test. That includes Florida … The test is also under consideration for coverage in Georgia, Massachusetts, New York, and North Carolina, according to the nonprofit Rady Children’s Institute for Genomic Medicine, another major provider of the test.”
“Collectively, these developments are encouraging children’s hospitals, academic centers, and tertiary care centers to look at establishing their own rWGS programs,” wrote Michel in The Dark Report. “In settings where this is appropriate, hospital and health system-based clinical laboratories have an opportunity to take an active role in helping jump start a newborn rWGS program in their institutions.”
Pathologists should continue to monitor rWGS, as well as prenatal and carrier testing, to have a full awareness of its growing use in infant and young child cancer screening.
