As 3D printing technology gains acceptance with pharmaceutical companies, clinical laboratories could see increased demand for pharmacogenomic testing
Will physicians someday “print” prescription drugs for patients in-office? It sounds like science fiction, but research being conducted at the University College London (UCL) indicates the capability may be closer than we think, and it could bring about a new type of collaboration between clinical laboratories, ordering physicians, and pharmacies.
UCL’s new 3D technique, which it calls “volumetric 3D printing,” is intended to enable the pharmaceutical industry to tailor drug dosage, shape/size, and release to an individual patient’s needs and preference. A key element of precision medicine.
According to GlobalData Healthcare, 3D printing also can “significantly reduce cost, wastes, and economic burden as printers only deposit the exact amount of raw materials required.”
3D printing may enable pharmaceutical companies to address gender and racial disparities in prescription drug manufacturing through a developing technology that could have implications for clinical laboratory testing. Fred Parietti, PhD (above), co-founder and CEO of Multiply Labs, a technology company that develops robotics for precision medicine pharmaceuticals, told 3D Natives, “Currently, medications are developed especially for white adult men, which means that all women and children have an excessive prescription for their bodies. This fact underlines the importance of the advent of personalized medicines, as well as highlighting the individuality of each patient, since the error in the dosage of certain active ingredients can even lead to the malfunctioning of some treatments.” (Photo copyright: Multiply Labs.)
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Increased Demand for Pharmacogenomic Testing
Though 3D printing of prescription drugs is not directly in the clinical laboratory/pathology space, it is noteworthy because it shows how technological advancements are progressing that actualize the ability to deliver precision medicine care to individual patients.
In turn, this could increase physician/patient demand for pharmacogenomic tests performed by clinical laboratories. The test results would be used by treating physicians to determine proper dosages for their individual patients prior to ordering 3D-printed drugs.
Being able to provide medication tailored to patients’ specific needs could bring about a revolution in pharmaceutical manufacturing. If 3D printed prescription drugs become mainstream, the demands could affect the clinical laboratory and pathology industries as well.
How Far Are We from Mass Production of 3D Printed Drugs?
The first and only 3D printed pharmaceutical drug on the American market is Spritam (levetiracetam) an anti-epileptic drug developed by Aprecia Pharmaceuticals, according to Medical Device Network. It received FDA clearance under the name Keppra in 1999.
Headquartered in Blue Ash, Ohio, Aprecia’s patented ZipDose manufacturing process allows 3D-printed pills to hold a larger dosage and dissolve rapidly. They currently have the only FDA process-validated 3D printing platform for commercial-scale drug production. They are leading the way on this new 3D technology and others are following suit.
FabRx, a start-up 3D printing company developed by academic researchers in 2014 at the University College London, released its first pharmaceutical 3D printer for personalized medicine called M3DIMAKER according to LabioTech.eu. The system is “controlled by specialized software, allowing the selection of the required dose by the pharmacist according to the prescription given by the clinician,” the company’s website notes.
The technology also allows for additional customization of pills, including the application of Braille for visually impaired patients, and printing of Polypills, which combine more than one drug into a single pill.
Other company’s developing 3D printing of pharmaceuticals, according to LabioTech.eu, include:
Germany’s Merck: currently in clinical trials of 3D printing medication with the goal of reaching large scale production.
China’s Triastek: which holds “41 patents that account for more than 20% of global 3D printing pharmaceuticals applications.”
We are still far away from large scale production of drugs using 3D printing, but that doesn’t mean it should not be on clinical laboratory leaders’ radar.
The rise of 3D printing technology for precision medicine could lead to big changes in the pharmaceutical world and alter how patients, providers, and clinical laboratories interact. It also could increase demand for pharmacogenomic testing to determine the best dosage for individual patients. This breakthrough shows how one line of technology research and development may, as it reaches clinical use, engage clinical laboratories.
University of Cincinnati researchers hypothesize that low levels of amyloid-beta protein, not amyloid plaques, are to blame
New research from the University of Cincinnati (UC) and Karolinska Institute in Sweden challenges the prevailing theory about the causes of Alzheimer’s disease, suggesting the possibility of new avenues for the development of effective clinical laboratory assays, as well as effective therapies for treating patients diagnosed with Alzheimer’s.
Scientists have long theorized that the disease is caused by a buildup of amyloid plaques in the brain. These plaques are hardened forms of the amyloid-beta protein, according to a UC news story.
“The paradox is that so many of us accrue plaques in our brains as we age, and yet so few of us with plaques go on to develop dementia,” said Alberto Espay, MD, one of the lead researchers of the study, in another UC news story. Espay is Professor of Neurology at the UC College of Medicine and Director and Endowed Chair of the Gardner Center for Parkinson’s Disease and Movement Disorders.
“Yet the plaques remain the center of our attention as it relates to biomarker development and therapeutic strategies,” he added.
“It’s only too logical, if you are detached from the biases that we’ve created for too long, that a neurodegenerative process is caused by something we lose, amyloid-beta, rather than something we gain, amyloid plaques,” said Alberto Espay, MD (above), in a University of Cincinnati news story. “Degeneration is a process of loss, and what we lose turns out to be much more important.” The UC study could lead to new clinical laboratory diagnostics, as well as treatments for Alzheimer’s and Parkinson’s diseases. (Photo copyright: University of Cincinnati.)
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High Levels of Aβ42 Associated with Lower Dementia Risk
In their retrospective longitudinal study, the UC researchers looked at clinical assessments of individuals participating in the Dominantly Inherited Alzheimer Network (DIAN) cohort study. DIAN is an ongoing effort, sponsored by the Washington University School of Medicine in St. Louis, to identify biomarkers associated with Alzheimer’s among people who carry Alzheimer’s mutations.
The researchers found that study participants with high levels of a soluble amyloid-beta protein, Aβ42, were less likely to develop dementia than those with lower levels of the protein, regardless of the levels of amyloid plaques in their brains or the amount of tau protein—either as phosphorylated tau (p-tau) or total tau (t-tau)—in their cerebral spinal fluid. P-tau and t-tau are proteins that form “tau tangles” in the brain that are also associated with Alzheimer’s.
One limitation of the study was that the researchers were unable to include Aβ40, another amyloid-beta protein, in their analysis. But they noted that this “did not limit the testing of our hypothesis since Aβ40 exhibits lower fibrillogenicity and lesser depletion than Aβ42, and is therefore less relevant to the process of protein aggregation than Aβ42.” Fibrillogenicity, in this context, refers to the process by which the amyloid-beta protein hardens into plaque.
While the presence of plaques may be correlated with Alzheimer’s, “Espay and his colleagues hypothesized that plaques are simply a consequence of the levels of soluble amyloid-beta in the brain decreasing,” UC news stated. “These levels decrease because the normal protein, under situations of biological, metabolic, or infectious stress, transform into the abnormal amyloid plaques.”
The UC News story also noted that many attempts to develop therapeutics for Alzheimer’s have focused on reducing amyloid plaques, but “in some clinical trials that reduced the levels of soluble amyloid-beta, patients showed worsening in clinical outcomes.”
New Therapeutics for Multiple Neurodegenerative Diseases
Eisai, a Japanese pharmaceutical company, recently announced phase three clinical trial results of lecanemab, an experimental drug jointly developed by Eisai and Biogen, claiming that the experimental Alzheimer’s drug modestly reduced cognitive decline in early-stage patients, according to NBC News.
Espay noted that lecanemab “does something that most other anti-amyloid treatments don’t do in addition to reducing amyloid: it increases the levels of the soluble amyloid-beta.” That may slow the process of soluble proteins hardening into plaques.
Beyond their findings about Alzheimer’s, the researchers believe similar mechanisms could be at work in other neurodegenerative diseases such as Parkinson’s disease, where the soluble alpha-synuclein protein also hardens into deposits.
“We’re advocating that what may be more meaningful across all degenerative diseases is the loss of normal proteins rather than the measurable fraction of abnormal proteins,” Espay said. “The net effect is a loss not a gain of proteins as the brain continues to shrink as these diseases progress.”
Espay foresees two approaches to treating these diseases: Rescue medicine, perhaps based on increasing levels of important proteins, and precision medicine, which “entails going deeper to understand what is causing levels of soluble amyloid-beta to decrease in the first place, whether it is a virus, a toxin, a nanoparticle, or a biological or genetic process,” according to UC News. “If the root cause is addressed, the levels of the protein wouldn’t need to be boosted because there would be no transformation from soluble, normal proteins to amyloid plaques.”
Clinical Laboratory Impact
What does this mean for clinical laboratories engaged in treatment of both Alzheimer’s and Parkinson’s patients? A new understanding of the disease would create “the opportunity to identify new biomarkers and create new clinical laboratory tests that may help diagnose Alzheimer’s earlier in the disease progression, along with tests that help with the patient’s prognosis and monitoring his or her progression,” said Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report.
Given the incidence of Alzheimer’s disease in the population, any clinical laboratory test cleared by the FDA would be a frequently-ordered assay, Michel noted. It also would create the opportunity for pathologists and clinical laboratories to provide valuable interpretation about the test results to the ordering physicians.
Company also launches Amazon Clinic virtual healthcare services and announces it will terminate Amazon Care by end of year
Clinical laboratory leaders and pathologists may understandably struggle to keep abreast of Amazon’s moves in the healthcare space. For years, Amazon has tried to develop medical services that disrupt the US healthcare industry in the same way its digital book business upended traditional book publishing. It is clear that Amazon is heavily investing in healthcare ventures that deliver what it believes are better alternatives to existing primary care, clinical laboratory, and retail pharmacy options.
Now, the Seattle-based global e-commerce company has announced plans to acquire One Medical, a membership-based primary care organization, for $3.9 billion according to a news release.
Headquartered in San Francisco, One Medical has primary care offices in 12 major US markets and offers its members 24/7 virtual care, according to the company’s website.
“We think healthcare is high on the list of experiences that need reinvention,” said Neil Lindsay (above), SVP of Amazon Health Services, in a news release announcing the planned acquisition of One Medical. “We love inventing to make what should be easy easier, and we want to be one of the companies that helps dramatically improve the healthcare experience over the next several years,” he added. However, clinical laboratory leaders have watched Amazon’s efforts to disrupt healthcare come and go. (Photo copyright: Advertising Age/Daniel Berman.)
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As One Medical Grows, Amazon Launches Virtual Care Clinic
“One Medical’s philosophy is rooted in quality care, patient-centered design, and a smart application of technology,” Greg Hayes, MD, District Medical Director for One Medical, Preston Center, Dallas, told Texas News.
For its part, One Medical, which currently has more than 125 clinic locations, sees opportunity to grow its services as part of Amazon (NASDAQ:AMZN). “Joining Amazon is a tremendous next step in innovating and expanding access to high-quality, high-value healthcare,” said Amir Dan Rubin, One Medical Chief Executive Officer, in a blog post.
One Medical (NASDAQ:ONEM) is the operating name for 1Life Healthcare, Inc., a chain of primary care clinics that has 815,000 members, a 14% increase over last year. According to a news release on the company’s third quarter 2022 financial results, its revenue was $261.4 million, up 73% over the same period last year. More than 8,000 companies and organizations work with One Medical, the company’s website notes.
Meanwhile, Amazon is also launching Amazon Clinic, a virtual health service “that delivers convenient, affordable care for common conditions” to people in 32 states, an Amazon news release states.
Amazon Clinic offers virtual care services for 20 common conditions including allergies, acne, migraines, and urinary tract infections. Patients complete a questionnaire through a message-based portal prior to meeting with clinicians.
Clinical laboratory managers and pathologists will want to note that Amazon Clinic will need medical laboratory testing performed to properly diagnose patients and determine the best treatments. Since Amazon Clinic will be a virtual care service, Amazon can be expected to explore such options as sending collection kits directly to individuals using the virtual care service, allowing them to collect needed samples that can be returned to traditional clinical laboratories for testing. Amazon’s existing courier and delivery service would make it easy for the internet giant to deliver either specimen collection kits or home-test kits to obtain the necessary diagnostic data.
“Amazon Pharmacy and One Medical (once the deal closes) are two key ways we’re working to make care more convenient and accessible. But we also know that sometimes you just need a quick interaction with a clinician for a common health concern. … That’s why today were also introducing Amazon Clinic, a message-based virtual care service,” Amazon said in its news release.
What’s Next for Amazon?
Separately, Amazon announced it will terminate Amazon Care at the end of 2022. Amazon Care is a virtual and in-home care service it launched in 2019.
However, in a 2022 internal email, senior vice president of Amazon Health Services Neil Lindsay said Amazon Care wasn’t a sustainable, long-term solution for its enterprise customers, according to Fierce Healthcare.
“This decision wasn’t made lightly and only became clear after many months of careful consideration,” he said. “Although our enrolled members have loved many aspects of Amazon Care, it is not a complete enough offering for the large enterprise customers we have been targeting and wasn’t going to work long-term.”
Will Amazon Provide Clinical Laboratory Services?
Now that Amazon is set with primary care, pharmacy, and virtual health services, might it next explore medical laboratory testing or other diagnostics relationships?
But this apparently has not slowed Amazon’s drive to gain a foothold in the primary care and virtual health services market. Therefore, clinical laboratory leaders should advance their outreach to healthcare providers who are caring for Amazon employees, customers, and soon patients, in new ways and offer their lab services.
Similar health monitoring devices have been popular with chronic disease patients and physicians who treat them; this technology may give clinical laboratories a new diagnostic tool
There is an ever-increasing number of companies working to develop lab testing technologies that would be used outside of the traditional clinical laboratory. One such example is Nutromics, an Australia-based medical technology company which recently announced it has raised US $14 million to fund its new lab-on-a-patch platform, according to a company press release.
Nutromics’ lab-on-a-patch device “uses DNA sensor technology to track multiple targets in the human body, including disease biomarkers and hard-to-dose drugs,” according to MobiHealthNews. Notably, Nutromics’ technology uses interstitial fluid as the sample source.
Nutromics raised $4 million last year to support a manufacturing facility and an initial human clinical trial of its “continuous molecular monitoring (CMM) platform technology that is able to track multiple targets in the human body via a single wearable sensor. The platform provides real-time, continuous molecular-level insights for remote patient monitoring and hospital-at-home systems,” MobiHealthNews reported.
“We are aiming to cause a paradigm shift in diagnostic healthcare by essentially developing a lab-on-a-patch. A lack of timely and continuous diagnostic insights can strongly impact outcomes when dealing with critical disease states. With this strategic industry and VC (venture capital) investment in us, we see more confidence in our technology and hope to accelerate our growth,” said entrepreneur and chemical engineer Peter Vranes (above), co-founder and CEO of Nutromics, in a press release. Clinical laboratory leaders have watched similar biometric monitoring devices come to fruition. (Photo copyright: Nutromics.)
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How Nutromics’ Lab-on-a-Patch Works
“Our technology is, in fact, two technologies coming together—a marker and needle. What that does is give us access to fluid under your skin called interstitial fluid. If you’re going to measure something continuously, that’s a really good fluid [to measure],” Vranes told Outcomes Rocket.
Vranes calls the system’s aptamer-based sensor platform technology the “jewel in the crown.” An aptamer is a short sequence of artificial DNA or RNA that binds a specific target molecule. Nutromics’ aptamer sensor, Vranes said, enables targeting of analytes, unlike continuous glucose monitors (CGMs).
“[CGMs] are limited to metabolites—things that are already in the body like glucose and lactate. We’re not limited to those. We can do a whole range of different targets. And what that gives us is a ‘blue ocean’ opportunity to go in and solve problems in areas that other technologies just can’t solve,” Vranes said.
Nutromics plans to develop multiple aptamer-based sensors that measure a variety of analytes in interstitial fluid, Medtech Insight noted.
Nutromics’ wearable DNA sensor lab-on-a-patch technology (above) enables monitoring of multiple targets, including disease biomarkers and some medications, MobiHealthNews explained. The wearable patch contains microneedles that painlessly access interstitial fluid under the skin. Collected data is wirelessly transmitted to a software application and integrates with consumer health software and provider platforms, according to Nutromics. Medical laboratories could have a role in collecting this data and adding it other test results from patients using the wearable patch. (Photo copyright: Nutromics.)
Initial Launch Will Include Antibiotic Monitoring
Nutromics expects to initially launch therapeutic monitoring of vancomycin, a glycopeptide antibiotic medication used to treat various bacterial infections. The company says 60% of doses for this prescription antibiotic are not within therapeutic range.
“Interstitial fluid originates in the blood and then leaks out of capillaries to bring nutrients to cells in the body’s tissues. Because interstitial fluid is in direct communication with the cells, it should have information about the tissues themselves beyond what can be measured from testing the blood,” said Mark Prausnitz, PhD, Regents Professor and J. Erskine Love Jr. Chair, Georgia Tech School of Chemical and Biomolecular Engineering, in a 2020 news release announcing results of human trials of microneedle-based ISF sampling.
“We sampled interstitial fluid from 21 human participants and identified clinically relevant and sometimes distinct biomarkers in interstitial fluid when compared to companion plasma samples based on mass spectrometry analysis,” the scientists wrote.
Clinical laboratory leaders and pathologists will find it useful to monitor the development of diagnostics for use outside the lab. Nutromics is an example of a company developing wearable health technology that painlessly gathers data for lab tests to be conducted in point-of-care and near-patient settings.
Studies could lead to new prognostic biomarkers and clinical laboratory diagnostics for cancer
Might fungi be involved in human cancers? Two separately published studies have found fungal DNA in various cancers in the human body. However, the researchers are unclear on how the fungi got into the cancer cells and if it is affecting the cancers’ pathology. Nevertheless, these discoveries could lead to utilizing tumor-associated fungal DNA as clinical laboratory diagnostics or prognostic biomarkers in the fight against cancer.
“The finding that fungi are commonly present in human tumors should drive us to better explore their potential effects and re-examine almost everything we know about cancer through a ‘microbiome lens,’” said Ravid Straussman, MD, PhD (above), a principal investigator at Weizmann Institute of Science and one of the authors of the study in a UCSD press release. These findings could lead to new clinical laboratory diagnostics and prognostic biomarkers. (Photo copyright: Weizmann Institute of Science.)
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Microbiome Key to Cancer Biology and Detection
To perform their research, the team examined 17,401 samples of patient tissues, blood, and plasma across 35 different types of cancers in four independent cohorts. They discovered fungal DNA and cells in low abundances in many human cancers.
“The existence of fungi in most human cancers is both a surprise and to be expected,” said biologist Rob Knight, PhD, founding Director of the Center for Microbiome Innovation and Professor of Pediatrics and Computer Science and Engineering at UC San Diego in a UCSD press release. “It is surprising because we don’t know how fungi could get into tumors throughout the body. But it is also expected because it fits the pattern of healthy microbiomes throughout the body, including the gut, mouth and skin, where bacteria and fungi interact as part of a complex community.”
The main highlights of this study include:
Fungi detected in the different cancer types were often intracellular.
Multiple fungal-bacterial-immune ecologies were detected across tumors.
Intratumoral fungi stratified clinical outcomes, including immunotherapy response.
Cell-free fungal DNA found in both healthy and cancer patients in early-stage disease.
Fungi found on the human body appear as either environmental fungi, such as yeasts and molds, and commensal fungi, which live either on or inside the body. Both are typically harmless to most healthy people and can provide some benefits, such as improving gut health, but they may also be a contributing factor in some disease.
The researchers found that there were notable parallels between specific fungi and certain factors, such as age, tumor subtypes, smoking status, immunotherapy responses, and survival measures.
“These findings validate the view that the microbiome in its entirety is a key piece of cancer biology and may present significant translational opportunities, not only in cancer detection, but also in other biotech applications related to drug development, cancer evolution, minimal residual disease, relapse, and companion diagnostics,” said Gregory Sepich-Poore, MD, PhD, one of the study’s authors and co-founder and chief analytics officer at biotechnology company Micronoma, in the UCSD press release.
New Clinical Laboratory Tests to Identify Fungal Species in Cancer
Researchers from Duke University and Cornell University uncovered compelling evidence of fungi in multiple cancer types and focused on a detected link between Candida and gastrointestinal cancers.
They found that “several Candida species were enriched in tumor samples and tumor-associated Candida DNA was predictive of decreased survival,” according to their paper.
Their analysis of multiple body sites revealed tumor-associated mycobiomes in fungal cells. The researchers found that fungal spores known as blastomyces were associated with tumor tissues in lung cancers, and that high rates of Candida were present in stomach and colon cancers.
The Duke/Cornell researchers hope their work can provide a framework to develop new tests that can distinguish fungal species in tumors and predict cancer progression and help medical professionals and patients chose the best treatment therapies.
“These findings open up a lot of exciting research directions, from the development of diagnostics and treatments to studies of the detailed biological mechanisms of fungal relationships to cancers,” said Iliyan Iliev, PhD, Associate Professor of Microbiology and Immunology in Medicine, Weill Cornell Medicine, and one of the authors of the study, in a Weill news release.
More research is needed to determine if fungal DNA plays a role in disease pathology or if its presence does not have any causal link.
“It’s plausible that some of these fungi are promoting tumor progression and metastasis, but even if they aren’t, they could be very valuable as prognostic indicators,” Iliev said.
The insights gleaned from these two studies will be of particular interest to microbiologists, clinical laboratory professionals, and anatomic pathologists. Additional research could answer questions about how and if fungi infect tumors and if such fungi is a factor that increases cancer risk and outcomes.
