With the ability to access critical biomarkers through the skin, this innovative patch from Georgetown researchers could shift the standard of care in diagnostics and drug delivery.
Researchers at Georgetown University have developed a technology that may replace the need for traditional blood testing: a non-invasive transdermal patch can detect biomarkers found in the bloodstream without drawing blood or inserting any devices into the body. The patch contains microheaters that reach 100 degrees Celsius to collect interstitial fluid from the surface of the skin.
Interstitial fluid is the vital liquid located in the spaces surrounding cells that transport oxygen and nutrients to cells throughout the human body, while removing waste products. The origin of this fluid is derived from blood plasma that leaks out of blood capillaries and eventually moves back into the bloodstream via the lymphatic system.
“The interstitial fluid, sometimes also called extracellular fluid, bathes every living cell in your body,” stated Makarand Paranjape, PhD, associate professor of physics and director of the Georgetown Nanoscience and Microfabrication Cleanroom Lab (GNuLab) in the College of Arts & Sciences in a news release. “It’s like a pre-filtered sample. When you draw blood, you have to filter down all the other stuff you don’t need. We don’t have to do that, so the interstitial fluid is ideal for detecting blood-borne biomarkers or biomolecules.”
The project originally began 25 years ago and was funded by the Department of Defense.
Over the past two decades, Paranjape has advanced this biomedical technology and built a portfolio of patents through Georgetown’s Office of Technology Commercialization, aiming to improve the quality of life for patients living with a broad range of chronic diseases.
Paranjape believes his patch, which he compares to a Band-Aid, will be beneficial for people who must have regular blood draws for disease maintenance and control, such as patients with diabetes, cancer, or heart disease.
Paranjape’s patch technology uses flexible polymers on an adhesive base, incorporating gold microheaters to create tiny pores in the skin, enabling the collection of interstitial fluid.
“You’re inserting a needle into your arm or abdomen and putting a sensor inside the body to detect blood glucose. Anytime you put something in your body, it’s going to be attacked by your own immune system,” he said.
Makarand Paranjape, PhD, associate professor of physics and director of the Georgetown Nanoscience and Microfabrication Cleanroom Lab (GNuLab) in the College of Arts & Sciences said, “When you’re talking about drug delivery and even monitoring biomolecules for diabetes, it’s all about the quality of life. Can that be improved? This technology, I feel, will do that.” (Photo credit: Georgetown University.)
Once the microheaters have been activated, the interstitial fluid exudes naturally from the pores in the skin and the patch is able to monitor biomarkers in the bloodstream. Because the temperatures applied to the skin and the generated micropores are shallow and do not reach nerve endings, the patch is pain-free. Patients also only need to change the patch once a day.
“That highly-controlled thermal pulse effectively removes only a microscopic portion of the top-most layer of dead skin. It’s essentially exfoliating that small area of skin to an extent that you’re creating a hair-sized micropore from the top of the skin extending to the living tissue,” Paranjape affirmed. “Once you get through that layer, there is plenty of interstitial fluid that actually comes up and out of the micropore since your heartbeat is providing pressure.”
Potential Beyond Diagnostics: A New Frontier for Drug Delivery
Paranjape developed the patch primarily with diabetics in mind but is hoping his device has further uses, including drug delivery. Transdermal patches for time-released drug delivery are available, yet this patch, according to Paranjape, is more effective as current patches on the market require existing drugs to be modified.
“Most of these patches require the drug in question to be tailored chemically to allow it to penetrate through intact skin. Ours does not,” he asserted. “We can use off-the-shelf drugs. We are creating tiny pores through the skin so the drug can easily enter and diffuse to the circulatory system.”
Paranjape also theorizes the patch could reduce pharmaceutical dosages, diminish medical waste and help curtail healthcare costs. His lab is currently working on adopting the patch for drug delivery in patients with Parkinson’s disease. He also plans to start a drug trial soon to help diagnose patients with cystic fibrosis.
Paranjape is hopeful that his patch-based platform technology will be utilized in the future to diagnose and treat patients with a wide array of illnesses and improve their quality of life.
“If there’s a marker in the blood that can be detected in the interstitial fluid, you can use the patch. If there’s a drug that can be used for the treatment of a condition, you can use the patch,” he said. “There’s a whole host of conditions that can be treated.”
Pharmaceutical and biotech researchers convened last week to discuss their latest work on targeting neurodegenerative diseases
With all the news this year alone on progress being made with diagnostic testing for Alzheimer’s disease, clinical laboratory professionals will be interested to know that drug discovery efforts to combat neurogenerative diseases are also at a heightened pitch.
Last week at the one-day Neuroimmunology in Drug Discovery forum in Boston, scientists learned about the latest advances in therapeutic research to better treat Alzheimer’s disease, multiple sclerosis, and Parkinson’s disease. As the treatments advance, demand for them will increase, which goes hand-in-hand with medical lab testing to detect signs of these illnesses.
The concern is urgent. The US Food and Drug Administration (FDA) noted that 10% of people age 65 and older have Alzheimer’s disease, and that number could double by 2050. The FDA recently cleared the first in vitro diagnostics device that tests blood to diagnose Alzheimer’s, and other IVD manufacturers and clinical labs are working on other Alzheimer’s tests, Dark Daily reported.
“It’s looking quite promising for NLRP3 inhibitors,” said Cheryl Leyns, PhD, associate principal scientist in discovery neuroscience at Merck Research Laboratories, in discussing how mutations of the NLRP3 protein can lead to neurodegenerative diseases. (Photo copyright: ELRIG.)
Much of the discussion at the Neuroimmunology in Drug Discovery forum centered on the idea that neuroinflammation—in other words, inflammation of the brain or spinal cord—starts well before neurodegenerative diseases arise. Neuroinflammation can accelerate Parkinson’s disease and other neurodegenerative disorders, said Cheryl Leyns, PhD, associate principal scientist, neuroimmunology, at Merck Research Laboratories in Boston, who spoke at the event.
From that perspective, drug discovery researchers are on the prowl for these early signs of future problems.
Leyns discussed NLRP3, a protein that aids the body’s inflammation process. A mutation of NLRP3 can lead to inflammatory problems, making the protein a prime target for researchers. “We have been interested, in the biopharma space, in the potential of NLRP3 inhibitors,” she noted.
Older Immune Systems Are Susceptible
While many in the public correctly associate Alzheimer’s with a person being outwardly older, a lesser-known aspect is that the body’s immune system also ages, becoming more susceptible over time to chronic inflammation.
Wailings’ assertion was not rhetorical. She pointed to numbers which showed scholarly research that involved the terms “inflammation,” “neurodegeneration,” and “aging” was only about 17% of the total amount of journal articles that addressed the first two terms, but which did not include “aging.”
As the pharmaceutical, biotech, and medical fields move aggressively forward to defend people against neurodegenerative diseases like Alzheimer’s, clinical laboratory scientists should take comfort that diagnostic testing trends are solidly in the mix.
Therapeutic advances, along with increased options for testing, show promising signs that patients and their caregivers will have more tools to use in the battle against these illnesses.
Findings may lead to new clinical laboratory testing and treatments for Parkinson’s patients
Gut bacteria have repeatedly been proven to perform critical roles in the development of certain diseases. And many clinical laboratory tests use human microbiota as biomarkers.
Now, researchers at Nagoya University Graduate School of Medicine in Japan have discovered a link between microbes in the gut and the brain. The connection may play a part in the development of Parkinson’s disease, according to a Nagoya University news release.
The researchers found that a reduction in the genes responsible for synthesizing riboflavin (vitamin B2) and biotin (vitamin B7) may increase the likelihood of developing Parkinson’s.
They also determined that the lack of these genes may lessen the integrity of the intestinal barrier that prevents toxins from entering the bloodstream causing the inflammation often seen in Parkinson’s patients.
“Supplementation therapy targeting riboflavin and biotin holds promise as a potential therapeutic avenue for alleviating Parkinson’s symptoms and slowing disease progression,” said lead researcher Hiroshi Nishiwaki, PhD, Division of Neurogenetics, Center for Neurological Diseases and Cancer, Nagoya University Graduate School of Medicine, in a news release. (Photo copyright: Nagoya University.)
Key Deficiencies in Parkinson’s Patients
According to the Parkinson’s Foundation, nearly one million people in the US are living with Parkinson’s and that number is expected to increase to 1.2 million by the year 2030. Approximately 90,000 new cases of Parkinson’s are diagnosed in the US each year, and more than 10 million people are living with the disease worldwide.
To perform their research, the Nagoya University team analyzed stool samples from 94 Parkinson’s patients from Japan, the US, Germany, China, and Taiwan. They also included 73 relatively healthy controls from Japan. They then used shotgun sequencing (a laboratory technique for determining the DNA sequence of an organism’s genome) to gain a better understanding of the microbial community and genetic makeup of each sample.
The scientists discovered a decrease in B2 and B7 vitamins in patients diagnosed with Parkinson’s. B vitamins promote the production and functions of short-chain fatty acids (SCFA) and polyamines.
“Supplementation of riboflavin and/or biotin is likely to be beneficial in a subset of Parkinson’s disease patients, in which gut dysbiosis plays pivotal roles,” the authors wrote in NPJ-Parkinson’s Disease.
The examination of fecal metabolites in Parkinson’s patients revealed a reduction in both components.
“Deficiencies in polyamines and SCFAs could lead to thinning of the intestinal mucus layer, increasing intestinal permeability, both of which have been observed in Parkinson’s,” said Hiroshi Nishiwaki, PhD, a professor at Nagoya University Graduate School of Medicine and a lead researcher for the study, in the news release.
“This higher permeability exposes nerves to toxins, contributing to abnormal aggregation of alpha-synuclein, activating the immune cells in the brain, and leading to long-term inflammation,” he added.
The team surmises that the weakened protective layer in the gut exposes the intestinal nervous system to more of the toxins people experience in everyday life, such as chemicals, pesticides, and herbicides. These types of toxins lead to the overproduction of alpha-synuclein fibrils. These molecules are aggregates of the α-synuclein protein that form into long, thread-like structures which are primarily found in the brains of individuals with neurodegenerative diseases like Parkinson’s.
Alpha-synuclein fibrils amass in dopamine-producing cells in the brain and increase the type of inflammation that leads to the debilitating motor skills and dementia symptoms of Parkinson’s.
Precision Medicine Analysis Suggested
Due to their research, the team proposes that high doses of vitamin B may help reduce the damage of toxins on the gut microbiome, help protect against neurodegenerative diseases like Parkinson’s, and aid in the creation of personalized therapy plans for patients.
“We could perform gut microbiota analysis on patients or conduct fecal metabolite analysis,” Nishiwaki noted. “Using these findings, we could identify individuals with specific deficiencies and administer oral riboflavin and biotin supplements to those with decreased levels, potentially creating an effective treatment.”
The results of the Nagoya University study illustrate the importance of a healthy gut microbiome in the prevention of disease. Altering the bacterial level in the gut may enable doctors to stave off the progression of neurodegenerative illnesses like Parkinson’s disease.
Findings could lead to clinical laboratory tests that help physicians identify microbes lacking in the microbiomes of their Parkinson patients
Microbiologists and clinical laboratory scientists know that gut microbiome can be involved in the development of Parkinson’s disease, a progressive neurological disorder that affects the nervous system due to damage caused to nerve cells in the brain. There is no cure for the illness. But a new treatment developed by researchers at the VIB Center for Inflammation Research at the University of Ghent in Belgium, may help to alleviate the symptoms.
During a clinical trial, VIB Center for Inflammation Research (VIB-IRC) scientists discovered that fecal microbiota transplantation (FMT), also known as a stool transplant, can improve motor skills in some Parkinson’s patients, according to Neuroscience News.
Parkinson’s disease (PD) develops when a protein called alpha-synuclein misfolds and forms into bundled clusters damaging nerve cells in the brain that produce dopamine. These formations, which are believed to appear in the gastrointestinal wall in the early stages of PD, then reach the brain via the vagus nerve leading to typical PD symptoms in patients.
“Our study provides promising hints that FMT can be a valuable new treatment for Parkinson’s disease,” Roosmarijn Vandenbroucke, PhD (above), Principal Investigator, VIB-UGent Center for Inflammation Research and full professor, UGent Department of Biomedical molecular biology, Faculty of Sciences, told Neuroscience News. “More research is needed, but it offers a potentially safe, effective, and cost-effective way to improve symptoms and quality of life for millions of people with Parkinson’s disease worldwide.” Clinical laboratories will likely be involved in identifying the best microbes for the FMT treatments. (Photo copyright: University of Ghent.)
Correlation between Gut Microbiome and Neurogenerative Disease
To perform their clinical study—referred to as GUT-PARFECT—the IRC researchers first recruited patients with early-stage PD and healthy donors who provided stool samples to the Ghent Stool Bank. The PD patients received the healthy stool via a tube inserted into the nose which led directly into the small intestine.
The FMT procedures were performed on 46 patients with PD between December 2020 and December 2021. The participants in this group ranged in ages from 50 to 65. There were 24 PD patients in the placebo group, and a total of 22 donors provided the healthy stool. Clinical evaluations were performed at baseline, three, six, and 12 months.
After 12 months, the group that received the transplants showed a reduction in symptoms compared to the placebo group. Their motor score on the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) improved by a mean of 5.8 points. The improvement registered on the same scale for the placebo group was 2.7 points.
Developed in the 1980s, the MDS-UPDRS is a scale utilized to evaluate various aspects of PD by measuring patient responses via a questionnaire rating several issues (such as cognitive impairment, apathy, depression, and anxiousness) common in PD patients from normal to severe. It is divided into four parts:
Part I: Non-motor experiences of daily living.
Part II: Motor experiences of daily living.
Part III: Motor examination.
Part IV: Motor complications.
During the final six months of the research, the improvement in motor symptoms became even greater. To the VIB-IRC researchers this implied that an FMT may have long-lasting effects on PD patients. The FMT study group also experienced less constipation, a condition that can be bothersome for some PD patients.
“Our results are really encouraging!” said the study’s first author, Arnout Bruggeman, MD, PhD student, VIB-UGent Center for Inflammation Research, in a UGent News release. “After twelve months, participants who received the healthy donor stool transplant showed a significant improvement in their motor score, the most important measure for Parkinson’s symptoms.”
Findings Could Lead to Other Targeted Therapies for PD
The VIB-IRC researchers believe there is a correlation between the gut microbiome and Parkinson’s disease.
“Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages,” the IRC researchers wrote in eClinicalMedicine.
“Our next step is to obtain funding to determine which bacteria have a positive influence. This could lead to the development of a ‘bacterial pill’ or other targeted therapy that could replace FMT in the future,” Debby Laukens, PhD, Associate Professor, Ghent University, told Neuroscience News.
According to the Parkinson’s Foundation website, nearly one million people in the US live with PD. It is second only to Alzheimer’s disease in the category of neurodegenerative diseases.
More research and studies are needed before the VIB-IRC’s stool transplant treatment can be used in clinical care. As researchers learn more about which specific strains of bacteria are doing the beneficial work in PD patients, that data could eventually lead to clinical laboratory tests performed to help physicians identify which microbes are lacking in the microbiomes of their PD patients, and if fecal transplants could help those patients.
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.
