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AXIM Biotechnologies Develops Diagnostic Test for Parkinson’s Disease That Uses Tear Drop Specimens and Returns Results in Less than 10 Minutes at the Point of Care

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.

A recent study conducted by the Michael J. Fox Foundation for Parkinson’s Research published in The Lancet Neurology titled, “Assessment of Heterogeneity among Participants in the Parkinson’s Progression Markers Initiative Cohort Using Α-Synuclein Seed Amplification: A Cross-Sectional Study,” found that “the presence of abnormal alpha-synuclein was detected in an astonishing 93% of people with Parkinson’s who participated in the study,” the news release noted.

“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.”

AXIM acquired Advanced Tear Diagnostics, Birmingham, Ala., in 2021. As part of this acquisition, it obtained two US Food and Drug Administration-cleared tests for dry eye syndrome, Fierce Biotech reported.

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.

Why Tears for PD Test?

Mark Lew, MD, Professor of Clinical Neurology, University of Southern California Keck School of Medicine, published earlier studies about using tear samples as biomarkers for Parkinson’s disease.

“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.

—Donna Marie Pocius

Related Information:

Parkinson’s Disease Biomarker Found

AXIM Biotechnologies Develops First Non-Invasive, Rapid, Point-of-Care, Diagnostic Test for Parkinson’s Disease

Assessment of Heterogeneity Among Participants in the Parkinson’s Progression Markers Initiative Cohort Using A-Synuclein Seed Amplification: a Cross-sectional Study

Tear Drop Test is First Rapid, Point-of-Care Diagnostic for Parkinson’s Disease

New Test Aims to Spot Signs of Parkinson’s Disease within a Tear Drop

Motivations for Using Tears to Confirm Parkinson’s Disease Diagnosis

Tears—More to Them than Meets the Eye: Why Tears are a Good Source of Biomarkers in Parkinson’s Disease

Researchers at Stanford University Discover Gene Variant That Appears to Protect Individuals from Both Alzheimer’s and Parkinson’s Disease

Study findings may lead to new clinical laboratory tests, as well as vaccines and immunotherapies for neurodegenerative diseases

Research into the human genome continues to produce useful new insights. This time, a study led by researchers at Stanford University identified a genetic variation that is believed to help “slow or even stall” progression of neurodegenerative diseases, including Alzheimer’s and Parkinson’s, according to a press release. Because these genetic variations are common, it is likely that diagnostic tests can be developed for use by clinical laboratories.

Researchers at Stanford Medicine led the study which discovered that approximately one in five individuals carry the gene variant, a protective allele identified as DR4 (aka, HLA-DR4). It’s one of a large number of alleles found in a gene known as DRB1.

DRB1 is part of a family of genes collectively known as the human lymphocyte antigen complex or HLA. The HLA-DRB1 gene plays a crucial role in the ability of the immune system to see a cell’s inner contents.

The Stanford scientists published their findings in the journal PNAS titled, “Multiancestry Analysis of the HLA Locus in Alzheimer’s and Parkinson’s Diseases Uncovers a Shared Adaptive Immune Response Mediated by HLA-DRB1*04 Subtypes.” Approximately 160 researchers from roughly 25 countries contributed to the work. 

Emmanuel Mignot, MD, PhD

“In an earlier study, we’d found that carrying the DR4 allele seemed to protect against Parkinson’s disease,” said Emmanuel Mignot, MD, PhD (above), Director of the Stanford Center for Narcolepsy, in a Stanford press release. “Now, we’ve found a similar impact of DR4 on Alzheimer’s disease.” Clinical laboratories may soon have new vaccines for both neurodegenerative diseases. (Photo copyright: Stanford University.)


DR4 Found to Impact Both Parkinson’s and Alzheimer’s Diseases

To perform their research, the team examined a large collection of medical and genetic databases from 176,000 people who had either Alzheimer’s or Parkinson’s disease. The people involved in the study were from numerous countries located in East Asia, Europe, the Middle East and South America. Their genomes were then compared with people who did not have the diseases, focusing on the incidence and age of onset.

“In an earlier study we’d found that carrying the DR4 allele seemed to protect against Parkinson’s disease,” said Mignot in the Stanford press release. “Now, we’ve found a similar impact of DR4 on Alzheimer’s disease.”

The team found that about 20% to 30% of people carry DR4, and that they have around a 10% risk reduction for developing the two diseases. 

“That this protective factor for Parkinson’s wound up having the same protective effect with respect to Alzheimer’s floored me,” said Emmanuel Mignot, MD, PhD, the Craig Reynolds Professor of Sleep Medicine in the Department of Psychiatry and Behavioral Sciences at Stanford University and the Director of the Stanford Center for Narcolepsy, in the Stanford Medicine press release. “The night after we found that out, I couldn’t sleep.”

The scientists also analyzed data from autopsied brains of more than 7,000 Alzheimer’s patients and discovered that individuals who carry DR4 had fewer neurofibrillary tangles and that those tangles are composed mainly of modified tau proteins, a common biomarker for Alzheimer’s.

The presence of these tangles corresponds with the severity of Alzheimer’s disease. They are not typically seen in Parkinson’s patients, but the Stanford team found that Parkinson’s patients who did carry DR4 experienced later onset of symptoms.

Mignot stated that tau, which is essential in Alzheimer’s, may also play a role in Parkinson’s, but that further research is required to prove its function.

Both diseases are characterized by the progressive loss of certain nerve cells or neurons in the brain and are linked to an accumulation of abnormal proteins. The Stanford researchers suggested that the DR4 gene variant may help protect individuals from Alzheimer’s and Parkinson’s by preventing the buildup of tau proteins.

“This is a very interesting study, providing additional evidence of the involvement of the immune system in the pathogenesis of Alzheimer’s and Parkinson’s,” neurologist Wassim Elyaman, PhD, Assistant Professor of Neurological Sciences in Neurology, the Taub Institute and the Institute for Genomic Medicine at Columbia University, told Live Science.

New Vaccines and Immunotherapies

According to the Alzheimer’s Association, more than six million Americans are currently living with Alzheimer’s disease and approximately one in three Americans die with Alzheimer’s or another dementia. 

The Parkinson’s Foundation states that nearly one million Americans are currently living with Parkinson’s disease, and that number is expected to rise to 1.2 million by 2030. Parkinson’s is the second-most common neurodegenerative disease after Alzheimer’s disease.

Even though the genetic analysis of the Stanford research is strong, more immune cell and blood-based research is needed to definitively establish how tau is connected to the two diseases.

This research could have implications for clinical laboratories by giving them biomarkers for a useful new diagnostic test, particularly for diagnosing Alzheimer’s and Parkinson’s.

Further, Mignot suggested that an effective vaccine could delay the onset or slow the progression of both diseases. He hopes to test his hypothesis on genetically modified mice and eventually human subjects.

—JP Schlingman

Related Information:

Stanford Medicine-led Study Finds Genetic Factor Fends Off Alzheimer’s and Parkinson’s

Gene Variant Carried by One in Five People May Guard Against Alzheimer’s and Parkinson’s, Massive Study Finds

Multiancestry Analysis of the HLA Locus in Alzheimer’s and Parkinson’s Diseases Uncovers a Shared Adaptive Immune Response Mediated by HLA-DRB1*04 Subtypes

Alzheimer’s Disease: Tau Biology and Pathology

Tau Protein and Alzheimer’s Disease: What’s the Connection?

C₂N Diagnostics Releases PrecivityAD, the First Clinical Laboratory Blood Test for Alzheimer’s Disease

UK Researchers Develop Clinical Laboratory Diagnostic Skin Test for Parkinson’s Inspired by Woman’s Ability to Smell the Disease before Onset of Symptoms

An assay using mass spectrometry could go to clinical trial within two years

Dark Daily has regularly observed that humans generate a variety of volatile substances—particularly in breath—which can be used for diagnostic purposes. But what if people, like certain trained animals, could smell the presence of disease before the onset of symptoms? What types of clinical laboratory testing biomarkers could be developed based on human-generated volatile organic compounds?

In “Woman Who Can Smell Parkinson’s Disease in Patients Even Before Symptoms Appear May Help Researchers Develop New Clinical Laboratory Test,” Dark Daily covered the unique story of Joy Milne, a retired nurse from Perth, Scotland, who claimed she could “smell” her husband’s Parkinson’s disease a decade before he was diagnosed with the illness.

As strange as that may sound, Milne’s olfactory abilities were confirmed by researchers at the Center for Regenerative Medicine at the University of Edinburgh and have now led to a clinical laboratory diagnostic Parkinson’s test based on body odor.

Researchers at the University of Manchester (UM) in the United Kingdom (UK) say their “breakthrough” test to diagnose Parkinson’s disease “can diagnose disease from skin swabs in three minutes,” according to a university press release.

The researchers published their findings in JACS AU, a Journal of the American Chemical Society, titled, “Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease.”

Perdita Barran, PhD and Joy Milne

Perdita Barran, PhD (right), head of the University of Manchester research team that developed the mass spectrometry Parkinson’s test, is shown above with Joy Milne (left), the retired nurse from Scotland who inspired Barran’s team to develop a new Parkinson’s biomarker and method for identifying it. “We are tremendously excited by these results which take us closer to making a diagnostic test for Parkinson’s Disease that could be used in clinic,” she said in a press release. A viable clinical laboratory test for Parkinson’s disease is greatly needed, as more than 10 million people worldwide currently live with the neurodegenerative disorder. (Photo copyright: University of Manchester.)

Using Mass Spectrometry to Analyze Sebum

The UM scientists hypothesized that the smell could be due to sebum, a light oily substance on skin that was going through a chemical change due to the Parkinson’s disease, Hull Daily Mail explained.

Increased sebum, which is produced by the sebaceous glands, is a hallmark of Parkinson’s, the researchers noted.

Their new method involves analysis of sebum using mass spectrometry, according to the JACS AU paper. The method, the researchers claim, makes it possible to diagnose Parkinson’s disease from skin swabs in three minutes.

“There are no cures for Parkinson’s, but a confirmatory diagnosis would allow [Parkinson’s patients] to get the right treatment and get the drugs that will help to alleviate their symptoms,” Perdita Barran, PhD, told the Hull Daily Mail. Barran is Chair of Mass Spectrometry in the Department of Chemistry and Director of the Michael Barber Centre for Collaborative Mass Spectrometry at UM’s Manchester Institute of Biotechnology. “What we are now doing is seeing if (hospital laboratories) can do what we’ve done in a research lab in a hospital lab,” she added.

Sebum Analyzed with Mass Spectrometry

Parkinson’s disease—the world’s fastest growing neurodegenerative disorder—needs “robust biomarkers” that could advance detection and head off onset of motor symptoms such as tremor, rigidity, and postural instability, the researchers note in their paper.

Their recent study builds on earlier 2019 findings they published in ACS Central Science about volatile compounds in sebum possibly being used as Parkinson’s biomarkers.

“Sebum is an underexplored biofluid, which is readily obtained from non-invasive skin swabs, which primarily consists of a mixture of triglycerides, cholesterol, free fatty acids, waxy esters,  and squalene,” the researchers explained in their JACS AU paper. 

The scientists sought, “to develop a method to analyze sebum in its native state to facilitate rapid assessment of the Parkinson’s disease status. Paper spray ionization mass spectrometry, which allows the direct analysis of compounds from paper, has previously been demonstrated to detect small molecules from unprocessed biofluids, such as blood and urine, but not to date with sebum,” they wrote.

The UM researchers used mass spectrometry to analyze sebum collected on cotton swabs from the backs of 79 people with Parkinson’s and 71 healthy individuals, BBC Scotland News reported.

Depanjan Sarkar, PhD, Research Associate, University of Manchester, further explained the technique in the UM news release:

  • Sebum is taken from the swab to filter paper cut in a triangle.
  • Using a solvent and voltage, sebum compounds transfer into the mass spectrometer.

“When we did this, we found more than 4,000 unique compounds of which 500 are different between people with Parkinson’s compared to the control participants,” Sarkar said.

Fatty Acids Make Assay Possible

Could fatty acids pave the way to an assay? The UM researchers believe so.

“We have identified two classes of lipids, namely [triglycerides] and diglycerides, as components of human sebum that are significantly differentially expressed in PD,” the researchers wrote in JACS AU. “Non-invasive sampling followed by PS-IM-MS [paper spray-ion mobility–mass spectrometry] analysis targeting these compounds could provide an inexpensive assay to support clinical phenotyping for the confirmatory diagnosis of Parkinson’s disease.”

A clinical trial for their test, which costs about $20, may be done within two years in Manchester area, the Daily Mail reported.

When Dark Daily reported in 2020 on Joy Milne’s unique ability to smell her husband’s Parkinson’s disease before it was formally diagnosed, we predicted a diagnostic test for Parkinson’s may be years away. And here it is, albeit with regulatory clearance needed following clinical trials.

It may in fact be possible to leverage sebum analysis to detect other diseases, the UM researchers noted.

For diagnostics developers, this story of Joy Milne and her husband Les Milne is a useful example of how, in tracking the life of a specific patient with a specific disease and close family members, researchers were able to identify a new class of biomarkers that could be used in a diagnostic assay.

It will be interesting to follow the University of Manchester researchers in their quest for a diagnostic mass spectrometry clinical laboratory test for Parkinson’s disease. According to Parkinson’s Foundation statistics, about 10 million people worldwide live with the neurodegenerative disorder. Such a new diagnostic test could be vitally important to medical laboratory care, and to patients and their families.

-Donna Marie Pocius

Related Information:

That’s Breathtaking; Meet the Woman Who Sniffed Out Her Husband’s Parkinson’s and Now Experts Have Created First Ever Test Based on Odor That Alerted Her

Parkinson’s Breakthrough Can Diagnose Disease from Skin Swabs in Three Minutes

Test for Parkinson’s is Developed Thanks to Woman Who Can Smell the Disease; It Has Been Years in the Making

Paper Spray Ionization Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease

Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum

Parkinson’s Test: Woman Who Smelled Disease on Husband Helps Scientists

Woman Who Can Smell Parkinson’s Disease in Patients Even Before Symptoms Appear May Help Researchers Develop New Clinical Laboratory Test

German Scientists Train Dogs to Detect the Presence of COVID-19 in Saliva Samples; Can a Canine’s Nose Be as Accurate as Clinical Laboratory Testing?

Though only in the pilot study phase, results correlate with earlier studies where both dogs and humans were able to “smell” specific diseases in people

Man’s best friend has risked life and limb to save humans for centuries. Now, researchers in Germany have discovered that pooches may be useful in the fight against COVID-19 as well, along with the added benefit that such testing would be non-invasive. In fact, some people believe disease-sniffing dogs may give clinical laboratory testing a run for its money.

Further, even if this approach were not warranted as a clinical diagnostic procedure, trained dogs could be deployed at airports, train stations, sporting events, concerts, and other public places to identify individuals who may be positive for SARS-CoV-2, the coronavirus that causes the COVID-19 illness. Such an approach would make it feasible to “screen” large numbers of people as they are on the move. Those individuals could then undergo a more precise medical laboratory test as confirmation of infections.

In cooperation with Bundeswehr, the German Armed Forces, scientists at the University of Veterinary Medicine Hannover (TiHo), along with scientists from the Hannover Medical School and the University Medical Center Hamburg-Eppendorf, carried out a pilot study with eight specialized sniffer dogs from the Bundeswehr to find people infected with the coronavirus.

After only one week of training, the dogs were able to accurately detect the presence of the infection 94% of the time. 

According to a live interview, which featured Holger Volk, PhD, Department Chair and Clinical Director of the Small Animal Clinic at the University of Veterinary Medicine Hannover and Maren von Köckritz-Blickwede, PhD, Professor of Biochemistry of Infections and Head of Scientific Administration and Biosafety at the Research Center for Emerging Infections and Zoonoses at TiHo, “The samples were automatically distributed at random and neither the dog handlers involved nor the researchers on site knew which samples were positive and which were used for control purposes. The dogs were able to distinguish between samples from infected (positive) and non-infected (negative) individuals with an average sensitivity of 83% and a specificity of 96%. Sensitivity refers to the detection of positive samples. The specificity designates the detection of negative control samples.

The researchers published their findings, “Scent Dog Identification of Samples from COVID-19 Patients—A Pilot Study,” in the open access, peer-reviewed journal BMC Infectious Diseases in July.

In their published study, the authors wrote, “Within randomized and automated 1,012 sample presentations, dogs achieved an overall average detection rate of 94% with 157 correct indications of positive, 792 correct rejections of negative, 33 false positive and 30 false negative indications.” They concluded, “These preliminary findings indicate that trained detection dogs can identify respiratory secretion samples from hospitalized and clinically diseased SARS-CoV-2 infected individuals by discriminating between samples from SARS-CoV-2 infected patients and negative controls. This data may form the basis for the reliable screening method of SARS-CoV-2 infected people.”

In the live interview, Dr. Köckritz-Blickwede said, “We think that this works because the metabolic processes in the body of a diseased patient are completely changed,” adding, “We think that the dogs are able to detect a specific smell of the metabolic changes that occur in those patients.”

Holger Volk, PhD and medical dog an Australian Shepherd
“People have not really realized the potential the dog could have to detect disease from lung-diseased patients,” said Holger Volk, PhD (above with his dog Jo), Department Chair and Clinical Director of the Small Animal Clinic at the University of Veterinary Medicine Hannover and one of the authors of the paper, in a live interview. (Photo copyright: University of Veterinary Medicine Hannover.)

Using Dogs as Part of Clinical Laboratory Testing

The American Kennel Club (AKC) estimates that a dog’s sense of smell is 10,000 to 100,000 times greater than that of humans. This gives dog’s the ability to detect diseases in early stages of development.

“The next steps will be that we try to differentiate between sputum samples from COVID patients versus other diseases, like, for example from influenza patients,” said Köckritz-Blickwede. “That will be quite important to be able to differentiate that in the future.” 

“This method could be employed in public areas such as airports, sport events, borders or other mass gatherings as an addition to laboratory testing, helping to prevent further spreading of the virus or outbreaks,” the live interview description states.

During a pandemic, employers might be able to use dogs to screen employees as they arrive for work. Dogs also could be used as an alternative or in addition to clinical laboratory testing to help prevent the spread of COVID-19. But more work must be done.

“What has to be crystal clear is that this is just a pilot study,” said Volk.  “So, there is a lot of potential to take this further to really make it possible to use these dogs in the field.”

An article on the VCA Hospitals website, titled, “How Dogs Use Smell to Perceive the World,” states that dogs devote much of their brain power to the interpretation of smells and they have more than 100 million sensory receptor sites located in their nasal cavity.

By contrast, humans have only six million sensory receptor sites in their nasal cavity. The area of a dog’s brain that is dedicated to the analysis of odors is about 40 times larger than the comparable part of a human brain and dogs are capable of detecting odors thousands of times better than humans.

The article also further explains how dog’s olfactory glands are very unique when compared to other animals and humans. “Unlike humans, dogs have an additional olfactory tool that increases their ability to smell. Jacobson’s organ is a special part of the dog’s olfactory apparatus located inside the nasal cavity and opening into the roof of the mouth behind the upper incisors. This amazing organ serves as a secondary olfactory system designed specifically for chemical communication.

“The nerves from Jacobsen’s organ lead directly to the brain and are different from the other nerves in the nose in that they do not respond to ordinary smells. In fact, these nerve cells respond to a range of substances that often have no odor at all. In other words, they work to detect “undetectable” odors.”

VCA Hospitals is a chain of veterinary hospitals with more than 1,000 facilities located in 46 states and five Canadian provinces. 

C. diff-sniffing Beagle Dog
Could dogs help prevent hospital-acquired infections? It is an interesting question, and one that has been asked before. In “C. diff-sniffing Beagle Dog Could Lead to Better Infection Control Outcomes in Hospitals and Nursing Homes,” January 2013, Dark Daily reported on a beagle named Cliff (above), which could sniff out Clostridium difficile (C. diff), a potentially deadly bacteria. In a study conducted by researchers at Vrije University Medical Center (VUMC) in Amsterdam, Cliff detected C. diff in both stool samples and the air surrounding infected patients in hospitals. In one test, Cliff correctly identified 50 out of 50 stool samples that were C. diff positive. He correctly identified 47 of 50 negative samples. That’s a sensitivity rate of 100% and a specificity rate of 94%. (Photo copyright: ABC News.)

Dogs are amazing, that’s for sure. But for canines to become widely used to detect infections there would have to be a way to validate each dog’s ability to detect diseases, so that the diagnostics would be consistent across all the dogs being used.

So, while there appears to be potential for utilizing a dog’s uncanny sense of smell to detect disease—including COVID-19—more research is needed before development of clinical testing can take place.  And, perhaps, a set of canine billing codes.

—JP Schlingman

Related Information:

Dogs Are Able to Detect Presence of Coronavirus by Sniffing Human Saliva, New Study Finds

Trained Dogs Were able to Sniff Out Covid-19 Infections with 94% Accuracy: Study

Scent Dog Identification of Samples from COVID-19 Patients – a Pilot Study

Dogs Detecting Disease: Meet America’s Cancer-Sniffing Canines

How Dogs Use Smell to Perceive the World

Live Interview: Diagnoses by Dog Noses—Dogs Can Sniff Out Patients with COVID-19

C. diff-sniffing Beagle Dog Could Lead to Better Infection Control Outcomes in Hospitals and Nursing Homes

Woman Who Can Smell Parkinson’s Disease in Patients Even Before Symptoms Appear May Help Researchers Develop New Clinical Laboratory Test

Woman Who Can Smell Parkinson’s Disease in Patients Even Before Symptoms Appear May Help Researchers Develop New Clinical Laboratory Test

She worked with researchers at the University of Manchester in England to identify volatile biomarkers for Parkinson’s disease that may lead to first noninvasive screening

Clinical pathologists and medical laboratories are used to working with certain biological indicators that drive diagnostics and clinical laboratory testing. Mostly, those biomarkers are contained within various liquid samples, such as blood and urine. But what if a person’s odor could accurately predict risk for certain diseases as well?

Far-fetched? That’s what Parkinson’s researcher Tilo Kunath, PhD, first thought when he was contacted by a woman who claimed she could “smell” Parkinson’s disease coming from her husband. Kunath is Group Leader, Reader in Regenerative Neurobiology, at the Center for Regenerative Medicine at the University of Edinburgh, and head of the Tilo Kunath Research Group, which focuses on how the protein, alpha-synuclein, causes degeneration of neurons in Parkinson’s patients, as well as on producing a cell-based therapy for Parkinson’s disease.

Joy Milne, a retired nurse from Perth, Scotland, is the women whose heightened sense of smell enabled her to detect her husband’s Parkinson’s a decade before he was diagnosed with the disease.

Of course, Milne did not know at the time that what she was smelling was in fact a disease. She told NPR that she first noticed that her husband’s smell had changed from “his lovely male musk smell,” which she’d noticed when they first met, into “this overpowering sort of nasty yeast smell.”

Frequent washing did not remove the odor and as time went on the smell became stronger. When aspects of her husband’s personality and sleep habits also began to change, Joy convinced her husband, Les Milne, an anesthetist, to seek a diagnosis, thinking he had a brain tumor. Les was diagnosed with Parkinson’s disease.

It was 20 years later, when the Milnes attended a Parkinson’s disease support group, that Joy recognized the same distinctive smell she had noticed on Les on the other members of the group. That’s when the Milnes first realized Joy’s heightened sense of smell was something quite unique and possibly unprecedented.  

Retired nurse Joy Milne of Perth, Scotland
Retired nurse Joy Milne (above) of Perth, Scotland, has an uncanny ability to diagnose Parkinson’s disease based on her highly sensitive sense of smell. Before her husband was diagnosed with the disease, she noticed a change in his smell. When she later recognized the same distinct odor among participants in a Parkinson’s support group, the Milnes asked scientists to investigate. (Photo copyright: NPR.)

Dogs Can Do It, Why Not Humans?

The concept that a disease gives off an aroma that can be detected by humans or animals is not far-fetched. As far back as 2013, Dark Daily was writing about such research. For example, in “C. diff-sniffing Beagle Dog Could Lead to Better Infection Control Outcomes in Hospitals and Nursing Homes,” we wrote about one hospital’s innovative approach to early detection of Clostridium difficile (C. diff) infection using a two-year-old beagle named Cliff that was faster at detecting certain infections than standard clinical laboratory tests used daily in hospitals throughout the world.

And in, “Researchers Determine That Individuals’ ‘Breathprints’ Are Unique; May Have Potential for Clinical Laboratory Testing When Coupled with Mass Spectrometry Technology,” we reported on research that showed a person’s breathprint is as unique as a fingerprint and may be as effective as bodily fluids in diagnosing diseases. The research also showed it was feasible to combine breath specimens and mass spectrometry to accurately identify disease, possibly leading to new diagnostic assays.

Thus, when the Milnes approached Dr. Kunath about Joy’s ability to “smell” Parkinson’s, they were on solid ground. However, he was not convinced.

“It just didn’t seem possible,” Kunath told NPR. “Why should Parkinson’s have an odor? You wouldn’t think neurodegenerative conditions such as Parkinson’s, or Alzheimer’s, would have an odor.”

But Kunath reconsidered after learning of research presented during the Experimental Biology annual meeting in 2019, which showed canines can in fact effectively detect lung cancer biomarkers in blood serum.

He contacted Milne and devised an experiment in which a group of people who had Parkinson’s disease, and another group that did not, would take home t-shirts and wear them overnight. The next day the t-shirts were assigned randomized numbers and put in a box. Milne then smelled each of the 12 t-shirts and assigned each one a score.

Kunath told NPR that Milne was “incredibly accurate.” She had misidentified only one shirt worn by a person in the control group. She incorrectly diagnosed the person with Parkinson’s. However, three months later, that man was in fact diagnosed with Parkinson’s, meaning Joy’s accuracy was 12-for-12.

“She was telling us this individual had Parkinson’s before he knew, before anybody knew,” Kunath told the BBC Scotland.

In an ensuing study, “Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum,” published in 2019 in ACS Central Science, the researchers describes the “distinct volatiles-associated signature” of Parkinson’s disease, which includes “altered levels of perillic aldehyde and eicosane, the smell of which was then described as being highly similar to the scent of Parkinson’s disease by our ‘Super Smeller.’” Joy Milne co-authored the study.

The concept of the human body producing volatile chemicals that can serve as biomarkers for disease or illness is not new to clinical laboratory professionals. The urea breath test, for example, to detect the presence of active H. pylori bacteria in the stomach is a longstanding example of one such diagnostic test.

Inspired by Milne’s accuracy, Kunath enlisted the help of Perdita Barran, PhD, Director of the Michael Barber Center for Collaborative Mass Spectrometry at the University of Manchester in England, to identify the specific compounds that contributed to the smell Joy had detected on her husband and the other Parkinson’s patients.

Barran led a larger Manchester University study which was published on ChemRxiv, titled, “Sebum: A Window into Dysregulation of Mitochondrial Metabolism in Parkinson’s Disease,” which was funded by a Michael J. Fox research grant (12921). Barran and her research team, which included Milne, “found 10 compounds linked to Parkinson’s by using mass spectrometry and other techniques” on skin sebum samples, reported NPR.

“We really want to know what is behind this and what are the molecules. And then, [determine if] the molecules [can] be used as some sort of diagnostic test,” Kunath told NPR.

A Definitive, Noninvasive Test for Parkinson’s?

The UK researchers discovered in the skin sebum volatile biomarkers of Parkinson’s disease that may lead to development of the first definitive test for the disease.

Katherine Crawford, Scotland Director of Parkinson’s UK, aka the Parkinson’s Disease Society of the United Kingdom, said a noninvasive diagnostic test for Parkinson’s would be game changing.

“We still effectively diagnose it today the way that Dr. James Parkinson diagnosed it in 1817, which is by observing people and their symptoms,” Crawford told BBC Scotland. “A diagnostic test like this could cut through so much of that, enable people to go in and see a consultant, have a simple swab test and come out with a clear diagnosis of Parkinson’s.”

“It wouldn’t have happened without Joy,” Barran told BBC Scotland. “For all the serendipity, it was Joy and Les who were absolutely convinced that what she could smell would be something that could be used in a clinical context, and so now we are beginning to do that.”

A viable, working diagnostic test based on these new biomarkers may be years away. Nevertheless, clinical laboratory leaders will want to follow the ongoing efforts toward development of a noninvasive swab test for Parkinson’s disease. Such a breakthrough would revolutionize Parkinson’s testing and might never have come to light without the persistence of a woman with an extremely sensitive sense of smell.

—Andrea Downing Peck

Related Information:

Her Incredible Sense of Smell Is Helping Scientists Find New Ways to Diagnose Disease

Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum

Parkinson’s Smell Test Explained by Science

Scientists Sniff Out Parkinson’s Disease Smell

The Woman Who Can Smell Parkinson’s Disease

Sebum: A Window into Dysregulation of Mitochondrial Metabolism in Parkinson’s Disease

Accuracy of Canine Scent Detection of Lung Cancer in Blood Serum

C. diff-sniffing Beagle Dog Could Lead to Better Infection Control Outcomes in Hospitals and Nursing Homes

Researchers Determine That Individuals’ ‘Breathprints’ Are Unique; May Have Potential for Clinical Laboratory Testing When Coupled with Mass Spectrometry Technology

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