A clinical trial that provided proactive personalized care to participants detected overlooked health conditions and risks

Physician Megan Mahoney examines Debbie Spaizman, who participated in the Humanwide pilot study.
Steve Fisch

A Stanford clinical trial that provided proactive, personalized care to participants detected overlooked health conditions and risks.

Stanford Medicine pilot program combining cutting-edge tools of biomedicine with a collaborative, team-based method, offers a new approach to personalized health care that captures the promise of Precision Health: to predict, prevent and treat disease based on the individual patient.

Through the Humanwide project, primary care teams at Stanford Medicine’s Primary Care 2.0 clinic in Santa Clara, California, merged high-tech and high-touch interventions to provide a diverse group of 50 patients with care that treated the whole person based on his or her unique factors, from genetics to lifestyle. Over the course of a year, the program succeeded in identifying previously undiagnosed conditions and future health risks, setting patients on a path to avert serious medical problems, such as cancer and heart disease.

“Our vision of Precision Health is to predict, prevent and cure — precisely,” said Lloyd Minor, MD, dean of the Stanford University School of Medicine. “With Humanwide, we have begun to realize that vision in a clinical setting. The information gathered in this pilot suggests approaches to primary care that may ultimately benefit thousands of people.”

A paper published May 13 in Annals of Family Medicine outlines initial learnings from Humanwide. The authors are Megan Mahoney, MD, Stanford Medicine’s chief of general primary care, and Steven Asch, MD, vice-chief of primary care and population health.

Mahoney, the lead investigator, said the Humanwide design shifts the focus of primary care to detecting disease earlier, strengthening the relationship between the patient and care team and deploying the latest health technology.

“With Humanwide, we’re able to focus on the whole human: who they are when they’re working, who they are when they’re playing, who they are when they’re at home,” she said. “This program demonstrates how we can zero in on what matters to a patient, to craft the entire care plan around their goals.”

Redesigning primary care

Humanwide was built on the foundation of Primary Care 2.0, the health care practice redesign effort at Stanford Medicine, where patients communicate regularly, in-person and virtually with members of a care team consisting of a primary care physician, nutritionist, behavioral health specialist and clinical pharmacist, depending on their health needs.

Patients in the Humanwide pilot represented a diverse mix of ages, races/ethnicities, genders and medical complexities. As part of the pilot, Humanwide patients:

  • Underwent genetic assessments and a pharmacogenomic screening, which evaluated their individual physiologic response to medications based on their genetic profile.
  • Used mobile monitoring devices, including a glucometer, pedometer, scale and blood pressure cuff, to regularly measure key health metrics. The data automatically uploaded to their electronic health records for remote monitoring by their health care team.
  • Worked with a certified health coach to identify wellness goals and create a plan for achieving them.

Through these initial assessments, regular interactions and continuous monitoring, health care teams gathered data on each patient on a variety of factors known to influence health: activity, behaviors, biometric measurement, genetic factors, biological markers, care-utilization data and environmental exposures.

Team members met regularly to review the multiple streams of data for each patient, and this continuous access to information and engagement with patients enabled them to pinpoint health risks and take preventive action.

“We saw this as an opportunity to bring in more data that was previously not available, so that we now have an unprecedented understanding of our patients’ risks,” Mahoney said. “Now we have the ability to proactively take care of them in a way we’ve never had before.”

Improvements in patient health

Through Humanwide’s comprehensive approach, Mahoney and her team detected and treated a range of health concerns previously overlooked. For example, among 33 women who were screened for breast cancer risk, five were identified as having a very high risk and in need of ongoing, enhanced surveillance.

Pharmacogenomics screening resulted in more than a dozen changes in medication prescriptions or dosages, including an adjustment that relieved pain for a patient experiencing persistent leg cramps from statins. Additionally, continuous readings from home-based devices helped providers identify early diabetes or hypertension in several patients and work with them to manage their risk. More extensive testing revealed masked hypertension in one patient who was at high risk of cardiovascular disease, and his team helped control his condition through medication and lifestyle changes.

Patients said they liked the strong connection with their care team and the opportunity to apply their personal data to their health.

“I loved the fact that you could get all of this precision health information to help your doctor and your caregiving team better pinpoint how to manage your health specific to you,” said participant Debbie Spaizman. “I got everything out of it that I had hoped for, and more.”

Another important finding involved provider satisfaction: Clinicians reported that they felt more engaged in their work when sharing the goal of caring for a patient with a like-minded team.

“Nearly half of all practicing physicians report at least one symptom of burnout, and that’s a huge concern for me,” Minor said. “That’s why it’s so important for programs like Humanwide to consider the experiences of both patients and physicians.”

Humanwide is an opportunity to build a deep understanding of each patient in a unique way.

David Entwistle, president and CEO of Stanford Health Care, said the pilot also paves the way for a new mindset about patient wellness.

“Looking at genomic data and other factors that actually predict patient health allows us to be proactive instead of waiting for something to happen and having to react to that,” he said. “Humanwide is an opportunity to build a deep understanding of each patient in a unique way.”

In their paper, Mahoney and Asch noted that the Humanwide pilot demonstrates the feasibility of creating a comprehensive, patient-centered, data-driven environment, and that both patients and health care providers are receptive to using new tools and data streams to transform primary care. Mahoney added that the project offers insights for the future use of detailed population health data to benefit individual patients.

Asch, who led evaluation of the pilot, said, “Humanwide is the future of primary care. It’s a future that looks at the patient as a whole person. It’s a future that collects data very broadly. And most importantly, it’s a future that helps the patient achieve their goals, rather than treating them like a collection of diseases.”

Videos, podcasts and other information about the pilot are available online.

Learn more: Stanford Medicine pilot program uses data-driven, integrated team approach to predict, prevent disease

 

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Scientists have identified how to halt kidney disease in a life-limiting genetic condition

via News-Medical.Net

For the first time scientists have identified how to halt kidney disease in a life-limiting genetic condition, which may pave the way for personalised treatment in the future.

Experts at Newcastle University, UK, have shown in a cell model and in a mouse model that gene editing could be used for Joubert syndrome to stop kidney damage in patients who have the CEP290 faulty gene.

Joubert syndrome is a brain disorder, causing varying degrees of physical, mental and sometimes visual impairments. The condition affects approximately one in 80,000 newborns, and one third also get kidney failure.

Not all patients with Joubert syndrome carry the CEP290 gene, but those who do will develop kidney disease during their lifetime and may require a transplant or dialysis.

Significant breakthrough

The study, which was funded by Kidney Research UK, has found it is possible to use a strand of engineered DNA to trick the cells’ own editing machinery to bypass the CEP290 mutation that causes kidney damage – a technique known as ‘exon-skipping’.

Professor John Sayer, from the Institute of Genetic Medicine, Newcastle University, led the research that is published online today (Friday, November 16) in the Proceedings of the National Academy of Sciences (PNAS).

He said: “This is the first time that gene editing within the kidney has been performed, even in a mouse model, as the design and delivery of the gene editing to the kidney has previously been thought to be too difficult.

“Our research is a major step forwards as we now know how we may be able to offer a therapy that corrects the gene mistake within kidney cells and prevent the development of genetic kidney disease.

“This work paves the way towards personalised genetic therapies in patients with the inherited kidney disease.”

The European study used kidney cells from patients with Joubert syndrome and a mouse model to progress the research.

Experts used urine samples to grow kidney cells in the laboratory to see how the cells responded to gene editing. They also performed gene editing to halt kidney disease in a mouse that had Joubert syndrome and rodents suffering from kidney cysts and kidney failure.

Challenging disease

Professor Sayer, a Consultant Nephrologist at Newcastle Hospitals NHS Foundation Trust, said: “The treatment of genetic kidney disease is challenging, as this requires both the correction of the underlying gene defect and the delivery of the treatment.

“We have shown that the kidney disease in a mouse can be dramatically improved using this exon-skipping gene editing technology.

“This will mean that we can edit out genetic mistakes that are leading to inherited kidney diseases such as Joubert syndrome and we are testing this technology in other mouse models before we move into patient studies.

“We expect that we will start to test treatment of patients with exon-skipping within the next three years.”

Scientists are now looking to work with a drug manufacturing company to bring the exon-skipping technology into patients’ clinics.

Patient’s story

Teenager Asher Ahmed has Joubert syndrome and is likely to need a kidney transplant in the future.

Asher, of Fenham, Newcastle, was diagnosed with kidney damage five years ago and is on a number of drugs to keep him well.

The 19-year-old has a range of medical issues due to his Joubert syndrome, including visual impairment, communication problems and difficulties with balance and coordination.

The teenager has been instrumental in helping further the research as he has provided many samples over the years, allowing the Newcastle scientists to grow kidney cells – without these the research would not have been possible.

Asher’s mother, Nabila, a Civil Servant, says she welcomes the findings of the Newcastle University-led study as it will help give patients a better quality of life in the future.

Mrs Ahmed said: “It is very important that research is done into Joubert syndrome and the linked kidney damage as this will hopefully prevent patients in the future needing a kidney transplant.

“All throughout Asher’s life, he has lived with the effects of Joubert syndrome and five years ago he was diagnosed with kidney disease as he has the CEP290 gene.

“Asher is on a number of tablets to keep him well and this is an added complication to an already difficult condition. We know he will likely need a transplant in the future and this is a worry.

“We were happy for Asher to provide samples for the study as anything that helps further understanding into the condition is well worth doing, so it’s great to see the study’s positive results.”

Learn more: Gene editing possible for kidney disease

 

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A new smart drainage device will help patients with glaucoma

The Purdue University glaucoma drainage device is built with microactuators that vibrate when a magnetic field is introduced. (Image provided by Hyowon Lee)

Purdue University Researchers have invented a new smart drainage device to help patients with glaucoma, a leading cause of blindness in the world, as they try to save their eyesight.

Glaucoma can be treated only with medications or surgical implants, both of which offer varying degrees of success in helping to improve sight and to relieve pressure buildup inside the eye. The U.S. Centers for Disease Control and Prevention says about 3 million Americans have glaucoma.

Implantable glaucoma drainage devices have grown in popularity over the past years, but only half of the devices are still operational after five years because microorganisms accumulate on the device during and after implantation. This problem is known as biofouling.

“We created a new drainage device that combats this problem of buildup by using advances in microtechnology,” said Hyowon “Hugh” Lee, an assistant professor in Purdue’s Weldon School of Biomedical Engineering and a researcher at the Birck Nanotechnology Center, who led the research team. “It is able to clear itself of harmful bio-buildup. This is a giant leap toward personalized medicine.”

The Purdue glaucoma drainage device is built with microactuators that vibrate when a magnetic field is introduced. The vibrations shake loose the biomaterials that have built up in the tube.

“We can introduce the magnetic field from outside the body at any time to essentially give the device a refresh,” Lee said. “Our on-demand technology allows for a more reliable, safe and effective implant for treating glaucoma.”

The Purdue technology is published in the latest issue of Microsystems and Nanoengineering. Another unique aspect of the Purdue device is its ability to vary flow resistance, which allows the drainage technology to customize treatment for each patient at different stages of glaucoma with varying degrees of pressure buildup inside the eye.

Other members of the Purdue research team include Arezoo Ardekani, an associate professor of mechanical engineering, and Simon John from the Jackson Laboratory.

The work aligns with Purdue’s Giant Leaps celebration, acknowledging the university’s global advancements in health as part of Purdue’s 150th anniversary. This is one of the four themes of the yearlong celebration’s Ideas Festival, designed to showcase Purdue as an intellectual center solving real-world issues.

Researchers are working with the Purdue Office of Technology Commercialization to patent the technology. They are looking for partners to license it.

Learn more: Purdue’s giant leap toward personalized medicine helps eyes drain themselves for glaucoma patients

 

 

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A pathway to personalized medicine and personalized biomanufacturing

via Phys.org

Engineering cellular biology, minus the actual cell, is a growing area of interest in biotechnology and synthetic biology. It’s known as cell-free protein synthesis, or CFPS, and it has potential to provide sustainable ways to make chemicals, medicines and biomaterials.

Unfortunately, a long-standing gap in cell-free systems is the ability to manufacture glycosylated proteins – proteins with a carbohydrate attachment. Glycosylation is crucial for a wide range of important biological processes, and the ability to understand and control this mechanism is vital for disease treatment and prevention.

Matthew DeLisa, the William L. Lewis Professor of Engineering in the Smith School of Chemical and Biomolecular Engineering, and Michael Jewett, associate professor of chemical and biological engineering at Northwestern University, have teamed up on a novel approach that bridges this gap. Their system, the first of its kind, capitalizes on the recent advances in CFPS while adding the crucial glycosylation component in a simplified, “one-pot” reaction. In the future, their cell-free glycoprotein synthesis system could be freeze-dried and reactivated for point-of-use protein synthesis by simply adding water.

DeLisa and Jewett are co-senior authors of “Single-pot Glycoprotein Biosynthesis Using a Cell-Free Transcription-Translation System Enriched with Glycosylation Machinery,” published July 12 in Nature Communications.

Thapakorn Jaroentomeechai, Ph.D. student in the DeLisa Research Group, and Jessica Stark ’12, Ph.D. student in the Jewett group, are co-first authors.

“If you really want to have a useful, portable and deployable vaccine or therapeutic protein technology that’s cell free, you have to figure out the carbohydrate attachment,” DeLisa said. “That’s, in essence, what we’ve done in a very powerful way.”

This work could impact development of decentralized manufacturing strategies. Rapid access to protein-based medicines in remote settings could change lives; new biomanufacturing paradigms suitable for use in low-resource settings might promote better access to costly drugs through local, small-batch production.

DeLisa has done a great deal of research on the molecular mechanisms underlying protein biogenesis in the complex environment of a living cell, such as Escherichia coli (E. coli). While his lab has made some notable breakthroughs, the limitations of this area, he said, are the cell walls themselves.

Jewett’s lab at Northwestern has invested much of its research efforts into cell-free synthetic biology, which leverages nature’s most elegant biomachinery outside the confines of the cell, so a collaboration was a natural extension of both labs’ work.

“In bacterial cell engineering, you’re constantly in a tug of war,” Jewett said. “You’re introducing a mechanism or capability that’s of interest to you as a scientist, but what the cell is trying to do for itself is grow and survive.”

For their new method, the team prepared cell extracts from an optimized laboratory strain of E. coli, CLM24, that were selectively enriched with key glycosylation components. The resulting extracts enabled a simplified reaction scheme, which the team has dubbed cell-free glycoprotein synthesis (CFGpS).

“A major advance of this work is that our cell-free extracts contain all of the molecular machinery for protein synthesis and protein glycosylation,” Stark said. “What that means is you only need to add DNA instructions for your protein of interest to make a glycoprotein in CFGpS. This is a drastic simplification from cell-based methods and allows us to make sophisticated glycoprotein molecules in less than a day.”

And the CFGpS method is highly modular, allowing for the use of distinct and diverse extracts to be mixed for the production of a variety of glycoproteins.

“Because we chose E. coli, which lacks its own glycosylation machinery, to build our CFGpS platform, it gave us a blank slate for bottom-up engineering of any desired glycosylation system,” Jaroentomeechai said. “This gives us the unique ability to control carbohydrate structures and purities of the glycoproteins at levels that are not currently achievable in other cell-based expression systems.”

Even in developed countries like the U.S., the move toward personalized medicine makes this type of on-demand drug production protocol attractive. “You could use a test tube instead of a 50,000-liter bioreactor to make your product, which opens the door to a personalized biomanufacturing paradigm where each patient can receive a unique protein medicine tailored to their physiology,” he said.

Learn more: Bioengineers create pathway to personalized medicine

 

 

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Brain tumor biopsy without surgery

via Medical Xpress

New technique developed at Washington University in St. Louis uses blood test

Taking a biopsy of a brain tumor is a complicated and invasive surgical process, but a team of researchers at Washington University in St. Louis is developing a way that allows them to detect tumor biomarkers through a simple blood test.

Hong Chen, a biomedical engineer, and Eric C. Leuthardt, MD, a neurosurgeon, led a team of engineers, physicians and researchers who have developed a groundbreaking, proof-of-concept technique that allows biomarkers from a brain tumor to pass through the tough blood-brain barrier into a patient’s blood using noninvasive focused ultrasound and some tiny bubbles, potentially eliminating the need for a surgical biopsy.

Chen, assistant professor of biomedical engineering in the School of Engineering & Applied Science and of radiation oncology in the School of Medicine, said while researchers have already learned how to get a drug through the blood-brain barrier into the brain via the bloodstream, no one — until now — has found a way to release tumor-specific biomarkers — in this case, messenger RNA (mRNA)— from the brain into the blood.

“I see a clear path for the clinical translation of this technique,” said Chen, an expert in ultrasound technology. “Blood-based liquid biopsies have been used in other cancers, but not in the brain. Our proposed technique may make it possible to perform a blood test for brain cancer patients.”

The blood test would reveal the amount of mRNA in the blood, which gives physicians specific information about the tumor that can help with diagnosis and treatment options.

Results of the study, which blends imaging, mechanobiology, genomics, immunology, bioinformatics, oncology, radiology and neurosurgery, are published in Scientific Reports April 26, 2018.

Chen; Leuthardt, professor of neurological surgery in the School of Medicine; and researchers from the Schools of Engineering & Applied Science and of Medicine, tested their theory in a mouse model using two different types of the deadly glioblastoma brain tumor. They targeted the tumor using focused ultrasound, a technique that uses ultrasonic energy to target tissue deep in the body without incisions or radiation. Similar to a magnifying glass that can focus sunlight to a tiny point, focused ultrasound concentrates ultrasound energy to a tiny point deep into the brain.

Once they had the target — in this case, the brain tumor — researchers then injected microbubbles that travel through the blood similar to red blood cells. When the microbubbles reached the target, they popped, causing tiny ruptures of the blood-brain barrier that allows the biomarkers from the brain tumor to pass through the barrier and release into the bloodstream. A blood sample can determine the biomarkers in the tumor.

This technique could lead to personalized medicine.

“In many ways this has been a holy grail for brain tumor therapy,” Leuthardt said. “Having the ability to monitor the changing molecular events of the tumor in an ongoing way allows us to not only better diagnose a tumor in the brain, but to follow its response to different types of treatment.”

“Once the blood-brain barrier is open, physicians can deliver drugs to the brain tumor,” Chen said. “Physicians can also collect the blood and detect the expression level of biomarkers in the patient. It enables them to perform molecular characterizations of the brain tumor from a blood draw and guide the choice of treatment for individual patients.”

In addition, Gavin Dunn, MD, assistant professor of neurosurgery, a co-author and leader in cancer immunobiology, plans to use the technique with immunotherapy, which offers precision treatment that targets specific biomarkers in the brain.

“This noninvasive focused ultrasound-enabled liquid biopsy technique can be useful for long-term monitoring of brain cancer treatment response, where repeated surgical tissue biopsies may not be feasible,” Chen said. “Meanwhile, variations within tumors pose a significant challenge to cancer biomarker research. Focused ultrasound can precisely target different locations of the tumor, thereby causing biomarkers to be released in a spatially-localized manner and allow us to better understand the spatial variations of the tumor and develop better treatment.”

The team continues to work to refine the process. The future will require integration with advanced genomic sequencing and bioinformatics to enable even more refined diagnostics. These efforts are being led by co-authors Allegra Petti, assistant professor of medicine, and Xiaowei Wang, associate professor of radiation oncology.

“Our ongoing work is to optimize the technique and evaluate its sensitivity and safety,” Chen said.

Learn more: Noninvasive brain tumor biopsy on the horizon

 

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