Already-existing clinical laboratory blood test may be new standard for detecting Alzheimer’s biomarkers
In Sweden, an independent study of an existing blood test for Alzheimer’s disease—called ALZpath—determined that this diagnostic assay appears to be “just as good as, if not surpass, lumbar punctures and expensive brain scans at detecting signs of Alzheimer’s in the brain,” according to a report published by The Guardian.
Alzheimer’s disease is one of the worst forms of dementia and it affects more than six million people annually according to the Alzheimer’s Association. Clinical laboratory testing to diagnose the illness traditionally involves painful, invasive spinal taps and brain scans. For that reason, researchers from the University of Gothenburg in Sweden wanted to evaluate the performance of the ALZpath test when compared to these other diagnostic procedures.
Motivated to seek a less costly, less painful, Alzheimer’s biomarker for clinical laboratory testing, neuroscientist Nicholas Ashton, PhD, Assistant Professor of Neurochemistry at the University of Gothenburg, led a team of scientists that looked at other common biomarkers used to identify changes in the brain of Alzheimer’s patients. That led them to tau protein-based blood tests and specifically to the ALZpath blood test for Alzheimer’s disease developed by ALZpath, Inc., of Carlsbad, Calif.
In their JAMA article, they wrote, “the pTau217 immunoassay showed similar accuracies to cerebrospinal fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies.”
In an earlier article published in medRxiv, Ashton et al wrote, “Phosphorylated tau (pTau) is a specific blood biomarker for Alzheimer’s disease (AD) pathology, with pTau217 considered to have the most utility. However, availability of pTau217 tests for research and clinical use has been limited.”
Thus, the discovery of an existing pTau217 assay (ALZpath) that is accessible and affordable is a boon to Alzheimer’s patients and to the doctors who treat them.
“The ALZpath pTau217 assay showed high diagnostic accuracy in identifying elevated amyloid (AUC, 0.92-0.96; 95%CI 0.89-0.99) and tau (AUC, 0.93-0.97; 95%CI 0.84-0.99) in the brain across all cohorts. These accuracies were significantly higher than other plasma biomarker combinations and equivalent to CSF [cerebrospinal fluid] biomarkers,” an ALZpath press release noted.
“This is an instrumental finding in blood-based biomarkers for Alzheimer’s, paving the way for the clinical use of the ALZpath pTau217 assay,” stated Henrik Zetterberg, MD, PhD (above), Professor of Neurochemistry at the University of Gothenburg and co-author of the study. “This robust assay is already used in multiple labs around the globe.” Clinical laboratories may soon be receiving doctors’ orders for pTau217 blood tests for Alzheimer’s patients. (Photo copyright: University of Gothenburg.)
Study Details
Ashton’s team conducted a cohort study that “examined data from three single-center observational cohorts.” The cohorts included:
“Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023,” the researchers wrote.
These trials from the US, Canada, and Spain featured 786 participants and featured “either a lumbar puncture or an amyloid PET scan to identify signs of amyloid and tau proteins—hallmarks of Alzheimer’s disease,” The Guardian reported, adding that results of the University of Gothenburg’s study showed that the ALZpath pTau217 blood test “was superior to brain atrophy assessments, in identifying signs of Alzheimer’s.”
“80% of individuals could be definitively diagnosed on a blood test without any other investigation,” Ashton told The Guardian.
Diagnosis Needed to Receive Alzheimer’s Disease Treatments
“If you’re going to receive [the new drugs], you need to prove that you have amyloid in the brain,” Ashton told The Guardian. “It’s just impossible to do spinal taps and brain scans on everyone that would need it worldwide. So, this is where the blood test [has] a huge potential.”
Even countries where such drugs were not yet available (like the UK) would benefit, Ashton said, because the test, “Could potentially say that this is not Alzheimer’s disease and it could be another type of dementia, which would help to direct the patient’s management and treatment routine.”
However, Ashton himself noted the limitations of the new findings—specifically that there is no success shown yet in Alzheimer’s drugs being taken by symptom-free individuals.
“If you do have amyloid in the brain at 50 years of age, the blood test will be positive,” he said. “But what we recommend, and what the guidelines recommend with these blood tests, is that these are to help clinicians—so someone must have had some objective concern that they have Alzheimer’s disease, or [that] their memory is declining,” he told The Guardian.
Experts on the Study Findings
“Blood tests could be used to screen everyone over 50-years old every few years, in much the same way as they are now screened for high cholesterol,” David Curtis, MD, PhD, Honorary Professor in the Genetics, Evolution and Environment department at University College London, told The Guardian.
“Results from these tests could be clear enough to not require further follow-up investigations for some people living with Alzheimer’s disease, which could speed up the diagnosis pathway significantly in future,” Richard Oakley, PhD, Associate Director of Research and Innovation at the Alzheimer’s Society, UK, told The Guardian.
Though Oakley found the findings promising, he pointed out what should come next. “We still need to see more research across different communities to understand how effective these blood tests are across everyone who lives with Alzheimer’s disease,” he said.
“Expanding access to this highly accurate Alzheimer’s disease biomarker is crucial for wider evaluation and implementation of AD blood tests,” the researchers wrote in JAMA Neurology.
“ALZpath makers are in discussions with labs in the UK to launch it for clinical use this year, and one of the co-authors, Henrik Zetterberg, MD, PhD, Professor of Neurochemistry at the University of Gothenburg, is making the assay available for research use as part of the ‘biomarker factory’ at UCL,” The Guardian reported.
In the US, to be prescribed any of the available Alzheimer’s medications, a doctor must diagnose that the patient has amyloid in the brain. A pTau217 diagnostic blood test could be used to make such a diagnosis. Currently, however, the test is only available “for research studies through select partner labs,” Time reported.
“But later this month, doctors in the US will be able to order the test for use with patients. (Some laboratory-developed tests performed by certain certified labs don’t require clearance from the US Food and Drug Administration.),” Time added.
It may be that the University of Gothenburg study will encourage Alzheimer’s doctors in the UK and around the world to consider ordering pTau217 diagnostic blood tests from clinical laboratories, rather than prescribing spinal taps and brains scans for their Alzheimer’s patients.
This pioneering innovation is consistent with the trend to bring medical services to places more convenient for consumers and was spurred by a study which showed men twice as likely to have heart attacks than women
Patient-facing healthcare gets a boost with this novel program to offer a diagnostic service in locations frequented by men. In an attempt to decrease heart attacks in the UK, the country’s National Health Service (NHS) now employs a novel approach to prevention—bringing blood pressure screenings to the public in barbershops.
This is yet another example of moving diagnostics services out of traditional healthcare settings and reaching people in places that they visit in their daily lives. True, this is a blood pressure test. But once the service is established, it should be easy to collect other types of clinical laboratory specimens at barbershops as well. And if this approach enables healthcare policy makers to reach a population that needs further diagnostic tests—and it’s economically feasible—that may encourage adoption of this approach for other types of health screenings.
According to The Guardian, the screenings will be available at “barbershops, churches, mosques, community centers, and dominoes clubs.” The intention is to ensure screenings are more accessible, to educate the public, and to encourage lifestyle changes that lead to prevention.
This consumer-directed approach to healthcare by the NHS appears to be making a difference. The new screening locations already show promise. In 2023, efforts brought in 150,000 community-based blood pressure screenings by August. That more than doubled the previous year’s 58,000 that were performed by May, The Guardian noted.
“With the number of people living with major illnesses including heart disease and other cardiovascular conditions set to grow substantially over the coming years, it has never been more important to put in place preventive measures like easy-to-access blood pressure checks that can pick up the early signs and risks,” said David Webb (above), Chief Pharmaceutical Officer for England, NHS England, in a news release. Should this program succeed, it’s likely other types of clinical laboratory test specimens could also be collected in barbershops and other convenient locations. (Photo copyright: Paul Stuart/The Pharmaceutical Journal.)
Importance of Screening
According to the UK’s Health Foundation, more than 9.1 million people will have a major illness by 2040, and figures show an increase of 2.5 million from 2019 reports. These figures are “why prevention and early intervention tools such as community blood pressure checks are key priorities for the NHS,” the NHS news release states.
“Having high blood pressure raises the risk of a heart attack, but many men and women remain unaware they may be affected because typically there are no symptoms,” The Guardian reported. “Every year there are 100,000 NHS hospital admissions due to heart attacks—one every five minutes.”
The NHS’ moves were spurred by recent findings announced at the European Society of Cardiology’s 2023 annual meeting. The world’s largest heart conference showcased a 22-year-long study examining the gender-specific risks of cardiovascular diseases. The results clearly showed that men were twice as likely to experience heart attacks and peripheral artery disease than women.
The University of Aberdeen conducted the study which ran from 1993-2018 and followed 20,000 individuals over the age of 40. While researchers noted many factors—such as ethnicity, body mass index (BMI), physical activity, deprivation, consumption of alcohol, and cigarette smoke—a clear defining line landed between male and female participants, The Guardian reported. Additionally,“Men are also more likely to experience a heart attack at a younger age than women.”
And, according to the study, while cardiovascular disease was higher for men during their entire lifetime, “sex differences were most pronounced for myocardial infarction and peripheral artery disease, followed by atrial fibrillation, heart failure, and cardiovascular mortality,” The Guardian reported, adding, “Men also have a 50% higher risk of heart failure and atrial fibrillation. The study discovered that men have a 42% higher risk of dying from cardiovascular disease. The research did not look at why.”
Education Part of Prevention
“Men should start looking early at-risk factors, like obesity, lack of exercise, smoking, alcohol consumption, and reach out to their GP to get those things addressed. The earlier the better. There’s no harm in minimizing your cardiovascular risk,” Tiberiu Pana, MRes, lead researcher and honorary research fellow at the University of Aberdeen, told The Guardian. Pana is also a junior doctor in the NHS and focuses on cardiovascular epidemiology and the brain-heart interactions.
“Coronary heart disease is the most common killer of men. There’s never been a better time to get physically active and replace that pub session with an extra session in the gym,” cardiologist Sonya Babu-Narayan, MBBS, Associate Medical Director at the British Heart Foundation, told The Guardian. Babu-Narayan is also a consultant cardiologist at Royal Brompton Hospital.
Women, however, are not exempt from the risk of heart disease.
“If we consider the effects of heart disease over a lifetime, we need to remember that it costs lives for both men and women,” Babu-Narayan said. “With 30,000 women in the UK admitted to hospital with a heart attack each year, it is vital to dismantle the dogma that heart attacks are the preserve of men. Regardless of gender, cardiovascular disease is the world’s biggest killer and there are steps everyone can take to reduce their risks.”
In addition to the aforementioned community locations for screenings, NHS has launched a few other approaches to meet patients on their own turf.
A mobile blood pressure service named How’s Thi Ticker in Barnsley, South Yorkshire, “travels around local neighborhoods including to barber shops, supermarkets, and community centers, seeing more than a third of people referred to pharmacists with high blood pressure—freeing up GPs and catching early signs of heart attack and stroke risk,” according to the NHS news release.
Future Showing Further Promise
As the process continues, NHS expects to prevent 1,350 cardiovascular events every year, and expects to see 2.5 million more blood pressure checks performed in the community in England as a result of the endeavor, The Guardian noted.
One can only imagine how far this trend can go. Clinical laboratory managers and pathologists can expect healthcare policy makers in the UK to continue their efforts to bring needed diagnostic testing to underserved populations in accessible ways. This should be a win-win financially and in improving the health of the country’s population.
Genetic engineers at the lab used the new tool to generate a catalog of 71 million possible missense variants, classifying 89% as either benign or pathogenic
Genetic engineers continue to use artificial intelligence (AI) and deep learning to develop research tools that have implications for clinical laboratories. The latest development involves Google’s DeepMind artificial intelligence lab which has created an AI tool that, they say, can predict whether a single-letter substitution in DNA—known as a missense variant (aka, missense mutation)—is likely to cause disease.
The Google engineers used their new model—dubbed AlphaMissense—to generate a catalog of 71 million possible missense variants. They were able to classify 89% as likely to be either benign or pathogenic mutations. That compares with just 0.1% that have been classified using conventional methods, according to the DeepMind engineers.
This is yet another example of how Google is investing to develop solutions for healthcare and medical care. In this case, DeepMind might find genetic sequences that are associated with disease or health conditions. In turn, these genetic sequences could eventually become biomarkers that clinical laboratories could use to help physicians make earlier, more accurate diagnoses and allow faster interventions that improve patient care.
“AI tools that can accurately predict the effect of variants have the power to accelerate research across fields from molecular biology to clinical and statistical genetics,” wrote Google DeepMind engineers Jun Cheng, PhD (left), and Žiga Avsec, PhD (right), in a blog post describing the new tool. Clinical laboratories benefit from the diagnostic biomarkers generated by this type of research. (Photo copyrights: LinkedIn.)
AI’s Effect on Genetic Research
Genetic experiments to identify which mutations cause disease are both costly and time-consuming, Google DeepMind engineers Jun Cheng, PhD, and Žiga Avsec, PhD, wrote in a blog post. However, artificial intelligence sped up that process considerably.
“By using AI predictions, researchers can get a preview of results for thousands of proteins at a time, which can help to prioritize resources and accelerate more complex studies,” they noted.
Of all possible 71 million variants, approximately 6%, or four million, have already been seen in humans, they wrote, noting that the average person carries more than 9,000. Most are benign, “but others are pathogenic and can severely disrupt protein function,” causing diseases such as cystic fibrosis, sickle-cell anemia, and cancer.
“A missense variant is a single letter substitution in DNA that results in a different amino acid within a protein,” Cheng and Avsec wrote in the blog post. “If you think of DNA as a language, switching one letter can change a word and alter the meaning of a sentence altogether. In this case, a substitution changes which amino acid is translated, which can affect the function of a protein.”
In the Google DeepMind study, AlphaMissense predicted that 57% of the 71 million variants are “likely benign,” 32% are “likely pathogenic,” and 11% are “uncertain.”
The AlphaMissense model is adapted from an earlier model called AlphaFold which uses amino acid genetic sequences to predict the structure of proteins.
“AlphaMissense was fed data on DNA from humans and closely related primates to learn which missense mutations are common, and therefore probably benign, and which are rare and potentially harmful,” The Guardian reported. “At the same time, the program familiarized itself with the ‘language’ of proteins by studying millions of protein sequences and learning what a ‘healthy’ protein looks like.”
The model assigned each variant a score between 0 and 1 to rate the likelihood of pathogenicity [the potential for a pathogen to cause disease]. “The continuous score allows users to choose a threshold for classifying variants as pathogenic or benign that matches their accuracy requirements,” Avsec and Cheng wrote in their blog post.
However, they also acknowledged that it doesn’t indicate exactly how the variation causes disease.
The engineers cautioned that the predictions in the catalog are not intended for clinical use. Instead, they “should be interpreted with other sources of evidence.” However, “this work has the potential to improve the diagnosis of rare genetic disorders, and help discover new disease-causing genes,” they noted.
Genomics England Sees a Helpful Tool
BBC noted that AlphaMissense has been tested by Genomics England, which works with the UK’s National Health Service. “The new tool is really bringing a new perspective to the data,” Ellen Thomas, PhD, Genomics England’s Deputy Chief Medical Officer, told the BBC. “It will help clinical scientists make sense of genetic data so that it is useful for patients and for their clinical teams.”
AlphaMissense is “a big step forward,” Ewan Birney, PhD, Deputy Director General of the European Molecular Biology Laboratory (EMBL) told the BBC. “It will help clinical researchers prioritize where to look to find areas that could cause disease.”
Other experts, however, who spoke with MIT Technology Review were less enthusiastic.
Heidi Rehm, PhD, co-director of the Program in Medical and Population Genetics at the Broad Institute, suggested that the DeepMind engineers overstated the certainty of the model’s predictions. She told the publication that she was “disappointed” that they labeled the variants as benign or pathogenic.
“The models are improving, but none are perfect, and they still don’t get you to pathogenic or not,” she said.
“Typically, experts don’t declare a mutation pathogenic until they have real-world data from patients, evidence of inheritance patterns in families, and lab tests—information that’s shared through public websites of variants such as ClinVar,” the MIT article noted.
Is AlphaMissense a Biosecurity Risk?
Although DeepMind has released its catalog of variations, MIT Technology Review notes that the lab isn’t releasing the entire AI model due to what it describes as a “biosecurity risk.”
The concern is that “bad actors” could try using it on non-human species, DeepMind said. But one anonymous expert described the restrictions “as a transparent effort to stop others from quickly deploying the model for their own uses,” the MIT article noted.
And so, genetics research takes a huge step forward thanks to Google DeepMind, artificial intelligence, and deep learning. Clinical laboratories and pathologists may soon have useful new tools that help healthcare provider diagnose diseases. Time will tell. But the developments are certain worth watching.
Millions of cancelled healthcare appointments and lengthy waits for care abound in UK, New Zealand, and in the US
Strikes continue on multiple continents as thousands of healthcare workers walk off the job. Doctors, medical laboratory scientists, nurses, phlebotomists and others around the world have taken to the picket lines complaining about low wages, inadequate staffing, and dangerous working conditions.
In England, junior doctors (the general equivalent of medical interns in the US) continue their uphill battle to have their complaints heard by the UK government. As a result, at hospitals and clinics throughout the United Kingdom, more than one million appointments have been cancelled due to strikes, according to the BBC.
“The true scale of the disruption is likely to be higher—many hospitals reduce bookings on strike days to minimize last-minute cancellations,” the BBC reported. “A total of one million hospital appointments have had to be rescheduled along with more than 60,000 community and mental health appointments since December [2022], when industrial action started in the National Health Service (NHS).”
According to The Standard, “Consultants in England are to be re-balloted over the prospect of further strike action as doctors and the government remain in talks with a view to end the dispute. The British Medical Association (BMA) said that specialist, associate specialist, and specialty (SAS) doctors will also be balloted over potential strike action.”
“We must be prepared to take the next step and ballot for industrial action if we absolutely have to—and we will do this … if upcoming negotiations fail to achieve anything for our profession,” Ujjwala Anand Mohite, DRCPath, FEBPath (above), a histopathologist at the NHS, Dudley Group of Hospitals, and the first female Chair of the SAS committee UK, told The Guardian.
New Zealand Doctors, Clinical Laboratory Workers Strike
In September, the first-ever nationwide senior doctor strike occurred in New Zealand and was then followed by another strike of about 5,000 doctors and 100 dentists from New Zealand’s public hospitals, the World Socialist Web Site reported.
Similar to the UK, the strikes reflect mounting frustration over pay not keeping up with inflation and “decades of deteriorating conditions in the public health system,” the WSWS noted.
This follows months of strikes by the island nation’s medical laboratory workers, which are ongoing.
“Our pay scales, if you compare them internationally, are not competitive. About half of our specialists come from abroad, so it’s quite important for the country’s health system to be able to attract and keep people,” Andy Davies, a lung specialist who joined the picket outside 484-bed Wellington Hospital, told the WSWS.
“We’re not asking for the world, we’re asking for an inflationary pay rise, and we haven’t had an inflationary pay rise year-on-year, and it’s beginning to show,” he added.
“What type of health system do they want?” he continued. “Do we want one that treats all people and manages what they need, or do we want a hacked down system that does less?”
The conflicts over pay and working conditions have caused many healthcare workers in New Zealand to leave the field entirely. This has led to severe shortages of qualified workers.
“Patient waiting times—for cancer, hip replacements, cardiac problems, and many other conditions—have exploded due to understaffed and overwhelmed hospitals,” the WSWS reported.
US Healthcare Workers also Striking
The US has its share of striking healthcare workers as well. Healthcare Dive tracked 23 ongoing or anticipated strikes throughout the nation’s healthcare industry since January 1, 2023. In 2022, there were 15 strikes of healthcare workers at the nation’s hospitals and health systems.
These walkouts include doctors, nurses, pharmacy workers, imaging specialists, and thousands of frontline healthcare workers striking over dangerously low staffing levels, unsafe working conditions, and low pay.
In October, 75,000 nurses, support staff, and medical technicians from Kaiser Permanente participated in a 72-hour strike comprised of hundreds of hospitals and clinics throughout California, Washington state, Oregon, Virginia, and the District of Columbia, Reuters reported.
The three-day strike, “Marked the largest work stoppage to date in the healthcare sector,” Reuters noted. Doctors, managers, and contingency workers were employed to keep hospitals and emergency departments functioning.
“The dispute is focused on workers’ demands for better pay and measures to ease chronic staff shortages and high turnover that union officials say has undermined patient care at Kaiser,” Reuters stated.
Staffing shortages following the COVID-19 pandemic are partly to blame for current struggles, but contract staffing to fill critical positions has exacerbated the problem.
“Kaiser’s outsourcing of healthcare duties to third-party vendors and subcontractors has also emerged as a major sticking point in talks that have dragged on for six months. … The clash has put Kaiser Permanente at the forefront of growing labor unrest in the healthcare industry—and across the US economy—driven by the erosion of workers’ earning power from inflation and pandemic-related disruptions in the workforce,” Reuters noted.
Across the globe, many healthcare workers—including clinical laboratory scientists in countries like New Zealand—are feeling burnt out from working in understaffed departments for inadequate pay. Hopefully, in response to these strikes, governments and healthcare leaders can come to resolutions that bring critical medical specialists back to work.
Research in the UK and US into how rapid WGS can prevent deaths and improve outcomes for kids with rare genetic diseases may lead to more genetic testing based in local clinical laboratories
Genetic scientists with the National Health Service (NHS) in England have embarked on an ambitious plan to offer rapid whole genome sequencing (rWGS) for children and babies with serious illnesses, as part of a larger initiative to embrace genomic medicine in the United Kingdom (UK).
The NHS estimates that the plan will benefit more than 1,000 children and babies each year, including newborns with rare diseases such as cancer, as well as kids placed in intensive care after being admitted to hospitals. Instead of waiting weeks for results from conventional tests, clinicians will be able to administer a simple blood test and get results within days, the NHS said in a press release.
The press release notes that about 75% of rare genetic diseases appear during childhood “and are responsible for almost a third of neonatal intensive care deaths.”
Here in the United States, pathologists and clinical laboratory managers should see this development as a progressive step toward expanding access to genetic tests and whole genome sequencing services. The UK is looking at this service as a nationwide service. By contrast, given the size of the population and geography of the United States, as this line of medical laboratory testing expands in the US, it will probably be centered in select regional centers of excellence.
“This strategy sets out how more people will be empowered to take preventative action following risk-based predictions, receive life-changing diagnoses, and get the support needed to live with genomically-informed diagnoses alongside improved access to cutting-edge precision [medicine] treatments. It also outlines how the NHS will accelerate future high-quality genomic innovation that can be adopted and spread across the country, leading to positive impacts for current and future generations,” the NHS wrote.
“This global first is an incredible moment for the NHS and will be revolutionary in helping us to rapidly diagnose the illnesses of thousands of seriously ill children and babies—saving countless lives in the years to come,” said NHS chief executive Amanda Pritchard (above) in a press release announcing the program. (Photo copyright: Hospital Times.)
New Rapid Whole Genome Sequencing Service
The NHS announced the plan following a series of trials last year. In one trial, a five-day old infant was admitted to a hospital in Cheltenham, Gloucester, with potentially deadly levels of ammonia in his blood. Whole genome sequencing revealed that changes in the CPS1 gene were preventing his body from breaking down nitrogen, which led to the spike in ammonia. He was given life-saving medication in advance of a liver transplant that doctors believed would cure the condition. Without the rapid genetic test, doctors likely would have performed an invasive liver biopsy.
Using a simple blood test, the new newborn genetic screening service in England is expected to benefit more than 1,000 critically ill infants each year, potentially saving their lives. “The rapid whole genome testing service will transform how rare genetic conditions are diagnosed,” explained Emma Baple, PhD, Professor of Genomic Medicine at University of Exeter Medical School and leader of the National Rapid Whole Genome Sequencing Service in the press release. “We know that with prompt and accurate diagnosis, conditions could be cured or better managed with the right clinical care, which would be life-altering—and potentially life-saving—for so many seriously unwell babies and children,” Precision Medicine Institute reported.
According to The Guardian, test results will be available in two to seven days.
Along with the new rWGS testing service, the NHS announced a five-year plan to implement genomic medicine more broadly. The provisions include establishment of an ethics advisory board, more training for NHS personnel, and an expansion of genomic testing within the existing NHS diagnostic infrastructure. The latter could include using NHS Community Diagnostics centers to collect blood samples from family members to test for inherited diseases.
UK’s Longtime Interest in Whole Genome Sequencing
The UK government has long been interested in the potential role of WGS for delivering better outcomes for patients with genetic diseases, The Guardian reported.
In 2013, the government launched the 100,000 Genomes Project to examine the usefulness of the technology. In November 2021, investigators with the project reported the results of a large pilot study in which they analyzed the genomes of 4,660 individuals with rare diseases. The study, published in the New England Journal of Medicine (NEJM) titled, “100,000 Genomes Pilot on Rare-Disease Diagnosis in Health Care—Preliminary Report,” found “a substantial increase in yield of genomic diagnoses made in patients with the use of genome sequencing across a broad spectrum of rare disease.”
The study’s findings suggest that use of WGS “could save the NHS millions of pounds,” The Guardian reported.
Whole Genome Sequencing System for Newborns in the US
“This NBS-rWGS [newborn screening by rapid whole genome sequencing] system is designed to complement the existing newborn screening process and has the potential to eliminate the diagnostic and therapeutic odyssey that many children and parents face,” Kingsmore said in a press release. “Currently, only 35 core genetic disorders are recommended for newborn screening in the United States, but there are more than 7,200 known genetic diseases. Outcomes remain poor for newborns with a genetic disease because of the limited number of recommended screenings. With NBS-rWGS, we can more quickly expand that number and therefore potentially improve outcomes through precision medicine.”
A more recent 2023 study which examined 112 infant deaths at Rady Children’s Hospital found that 40% of the babies had genetic diseases. In seven infants, genetic diseases were identified post-mortem, and in five of them “death might have been avoided had rapid, diagnostic WGS been performed at time of symptom onset or regional intensive care unit admission,” the authors wrote.
“Prior etiologic studies of infant mortality are generally retrospective, based on electronic health record and death certificate review, and without genome information, leading to underdiagnosis of genetic diseases,” said Christina Chambers, PhD, co-author of the study, in a press release. “In fact, prior studies show at least 30% of death certificates have inaccuracies. By implementing broad use of genome sequencing in newborns we might substantially reduce infant mortality.”
Pioneering work with whole genome sequencing for newborns, such as that being conducted by the clinical laboratory and genetic teams at Rady Children’s Hospital and the UK’s NHS, could allow doctors to make timely interventions for our most vulnerable patients.
