WHITE HOUSE FACT SHEET ON NEW PATIENT-FOCUSED COMMITMENTS

FROM:  THE WHITE HOUSE
FACT SHEET: New Patient-Focused Commitments to Advance the President’s Precision Medicine Initiative

“Doctors have always recognized that every patient is unique, and doctors have always tried to tailor their treatments as best they can to individuals. You can match a blood transfusion to a blood type — that was an important discovery. What if matching a cancer cure to our genetic code was just as easy, just as standard? What if figuring out the right dose of medicine was as simple as taking our temperature?” -- President Barack Obama, January 30, 2015

In January 2015, President Obama launched the Precision Medicine Initiative (PMI), a bold new research effort to revolutionize how we improve health and treat disease, empowering health care providers to tailor treatment and prevention strategies to individuals’ unique characteristics. In launching PMI, the President acknowledged that success in this effort will require all hands on deck – including the active participation of care providers, health professionals, researchers, innovators, patients, and research participants.

Today, marking six months of progress to advance PMI, the White House is hosting a Champions of Change event honoring extraordinary individuals from across the country who are making a difference in the lives of patients and driving precision medicine forward. In addition to celebrating these Champions, Federal agencies and private-sector groups are stepping up to the President’s call to action to advance the PMI by making important commitments to:

Make health data more portable;
Ensure patients can easily access and share their own health information, including contributing it for research;
Rigorously protect patient privacy, security and choice; and
Support new research platforms connecting researcher and participants as partners.
Administration commitments launching today include:

Guiding Principles for Protecting Privacy and Building Trust: Today, the White House is unveiling draft PMI guiding principles that seek to build privacy into the design of the PMI research cohort, which will include one million or more Americans who agree to share data about their health.   An interagency working group convened by the White House developed these principles out of a series of expert roundtables, review of the bioethics literature, analysis of existing privacy and trust frameworks, and working group discussions. The principles articulate a set of core values and responsible strategies for building public trust and maximizing the benefits of a large national research cohort, while minimizing the risks inherent in large-scale data collection, analysis and sharing.  The White House is seeking public feedback on the Privacy and Trust Principles online through August 7, 2015.

New Tools for Patients: In collaboration with federal partners, the Department of Health and Human Services Office of the National Coordinator for Health IT (ONC) and Office for Civil Rights (OCR) will work to address barriers that prevent patients from accessing their health data. OCR will develop additional guidance materials to educate the public and health care providers about a patient’s right to access his or her health information under the Health Insurance Portability and Accountability Act (HIPAA).  In collaboration with the White House Social and Behavioral Sciences Team, ONC will publish sample communications tools to encourage patients to access their digital health information and workflow diagrams for providers. These resources draw on extensive user research and proven practices to encourage patients to view, download, and transmit their health information. ONC is also developing an open-source prototype that will allow individuals to combine their medical records with patient-generated data and connect these data with the apps of their choice.

Research Awards to Unlock Data Insights: Today the Department of Veteran Affairs (VA) is announcing awards to support four research projects on key questions relevant to precision medicine using the rich data from the Million Veterans Program (MVP), the largest US repository of genetic, clinical, lifestyle and military exposure data. The projects, which focus on the genetic contributions of heart disease, kidney disease, and substance abuse, are designed to assess the utility and accessibility of the data captured in MVP, in addition to answering important scientific questions. These studies will also help inform plans for PMI’s national research cohort, including the types of data that should be included and the design of the data platform. To date, over 390,000 Veterans have enrolled in MVP, and have provided a blood sample, answered a health questionnaire, and authorized access to their electronic health records (EHRs). Understanding how these data, when combined, can help uncover new insights into factors that affect disease onset and progression will be an important test for all precision medicine focused cohorts.

Private-sector commitments launching today include:

Duke Center for Applied Genomics and Precision Medicine: Duke has developed a platform called MeTree that helps individuals have challenging but necessary conversations with loved ones and care providers about family health histories, so that physicians can tailor care to patients’ unique risk profiles. Duke is announcing that, leveraging emerging standards, MeTree will now connect with the information in patients’ electronic health records, allowing patients and providers to seamlessly access information in EHRs through application programming interfaces (APIs).  This effort aims to enrich communication between patients and their clinicians and to help them make the best possible care decisions as a team.

Flip the Clinic: Flip the Clinic, a project of the Robert Wood Johnson Foundation, is announcing a collaboration with more than 160,000 clinicians and staff practicing at sites across the United States, who have pledged to inform patients about their right to get digital copies of their medical records. Flip the Clinic will work hand-in-hand with clinicians at these sites to redesign how clinicians respond to patients’ requests for their own records, with the goal of making health-information access, sharing, downloading, and use a more seamless experience for both patients and clinicians. Flip the Clinic is further committing to educate patients about the President’s Precision Medicine Initiative and how to get involved. Collaborators in this effort include a wide range of delivery systems, clinics, organizations, and technology partners.

Genetic Alliance: Along with collaborators, Genetic Alliance is launching new capabilities for Platform for Engaging Everyone Responsibly (PEER), a data registry that empowers participants to share their data with medical researchers, advocacy groups, and others. With assistance from Cerner and NATE, going forward, PEER will accept coded, clinical data from participants’ electronic health records (EHRs). Participants will be able to send this information to PEER directly from their provider-supplied portals, leveraging national standards, or ask that their providers send it. PEER is a free-to-the-participant user service that is provided through condition-specific advocacy and support groups. Each participant is provided with tools to dynamically control how much of their information they wish to share, and with whom. Currently there are about 20 provider-supplied portals that work with PEER. Through a grant from the Robert Wood Johnson Foundation, this number will more than double by the end of 2015. Additional collaborators on this effort include: Private Access, Cerner Corporation, National Association of Trusted Identities (NATE).

GetMyHealthData: The GetMyHealthData campaign is pledging to help thousands of consumers over the next 12 months access and download their own clinical health data, so they can use it to understand and improve their health, their care, and the system as a whole -- including donating their data for research. The campaign is a collaboration of consumer organizations, health care experts, former policy makers and technology organizations.  GetMyHealthData will guide consumers through the often complex process by providing a tool to automate the request for their data and to troubleshoot any problems that occur. The initiative will also offer basic guidance on apps that can safely and securely store patient data, including those that enable data donation for research while protecting privacy. Finally, the campaign will provide resources for clinicians and consumers that explain consumers’ rights and best practices to get copies of their structured electronic clinical data. Collaborators include: National Partnership for Women & Families, Amida, Code for America, Genetic Alliance, Health Data Consortium and NATE.

Sage Bionetworks: Recognizing the importance of health-data liberation, and the role of data in driving research studies, Sage Bionetworks is announcing that it will support clinical studies that import electronic health-record information to its open source research platform and that it will release open-source informed-consent prototypes to support these studies. Sage’s goal is to catalyze new clinical studies that are native to mobile phones, vastly expanding the ability of citizens to voluntarily participate and engage as partners in research. Sage Bionetworks leverages the power of open networks of contributors to solve complex scientific problems, including the Cancer Genome Atlas and NIH’s Alzheimer’s Accelerating Medicine Partnership.

POLIO ERADICATION CAN BE STRENGTHENED BY IMPROVING QUALITY OF SURVEILLANCE FOR POLIOVIRUSES

FROM:  CENTERS FOR DISEASE CONTROL AND PREVENTION
Tracking Progress Toward Polio Eradication — Worldwide, 2013–2014
CDC Media Relations

Improvement in the quality of surveillance for polioviruses is needed to help strengthen global polio eradication efforts. There are only three countries where poliovirus circulation has never been interrupted: Afghanistan, Nigeria, and Pakistan. Outbreaks occurred during 2013 and 2014 as a result of spread from these countries. Monitoring the progress of the Global Polio Eradication Initiative requires sensitive and timely polio surveillance. This report presents 2013 and 2014 poliovirus surveillance data, focusing on reports during 2010-2014 from 29 countries with at least one case of wild or circulating vaccine-derived poliovirus. In 2013, 25 of the 29 countries met the two primary surveillance quality indicators: sensitivity and timeliness; in 2014, the number decreased to 21. To complete and certify polio eradication, gaps in surveillance must be identified and surveillance activities, including supervision, monitoring, and proper specimen collection, must be further strengthened.

CDC SAYS EXPANDED USE OF NALOXONE COULD REDUCE DEATHS FROM DRUG OVERDOSES

FROM:  U.S. CENTERS FOR DISEASE CONTROL AND PREVENTION
Expanding Naloxone use could reduce drug overdose deaths and save lives
Where you live makes a difference

Allowing more basic emergency medical service (EMS) staff to administer naloxone could reduce drug overdose deaths that involve opioids, according to a Centers for Disease Control and Prevention (CDC) study, “Disparity in Naloxone Administration by Emergency Medical Service Providers and the Burden of Drug Overdose in Rural Communities,” published in the American Journal of Public Health.

In 2013, more than 16,000 deaths in the United States involved prescription opioids, and more than 8,000 others were related to heroin.  Naloxone is a prescription drug that can reverse the effects of prescription opioid and heroin overdose, and can be life-saving if administered in time.

According to the study findings, advanced EMS staff were more likely than basic EMS staff to administer naloxone.  A majority of states have adopted national guidelines that prohibit basic EMS staff from administering the drug as an injection. As of 2014, only 12 states allowed basic EMS staff to administer naloxone for a suspected opioid overdose; all 50 states allow advanced EMS staff to administer the overdose reversal treatment.

“Opioid overdose deaths are devastating families and communities, especially in rural areas,” said CDC Director Tom Frieden, M.D., M.P.H.  “Many of these deaths can be prevented by improving prescribing practices to prevent opioid addiction, expanding the use of medication-assisted treatment, and increasing use of naloxone for suspected overdoses. Having trained EMS staff to administer naloxone in rural areas will save lives.”

To reduce opioid overdose deaths, particularly in rural areas, CDC recommends expanding training on the administration of naloxone to all emergency service staff, and helping basic EMS personnel meet the advanced certification requirements.

CDC ANNOUNCES EBOLA VACCINE TRIAL HAS BEGUN IN SIERRA LEONE

FROM:  CENTERS FOR DISEASE CONTROL AND PREVENTION
Ebola vaccine trial begins in Sierra Leone
6,000 health and other front-line workers will receive vaccine in five districts of the country

The Centers for Disease Control and Prevention (CDC), in partnership with the Sierra Leone College of Medicine and Allied Health Sciences (COMAHS) and the Sierra Leone Ministry of Health and Sanitation (MoHS), is now enrolling and vaccinating volunteers for the Sierra Leone Trial to Introduce a Vaccine against Ebola (STRIVE). This study will assess the safety and efficacy of the rVSV-ZEBOV candidate Ebola vaccine among health and other frontline workers.

“A safe and effective vaccine would be a very important tool to stop Ebola in the future, and the frontline workers who are volunteering to participate are making a decision that could benefit health care professionals and communities wherever Ebola is a risk,” said CDC Director Tom Frieden, M.D., M.P.H.  “We hope this vaccine will be proven effective but in the meantime we must continue doing everything necessary to stop this epidemic —find every case, isolate and treat, safely and respectfully bury the dead, and find every single contact.”

STRIVE will enroll about 6,000 health and other frontline workers. It will be conducted in Western Area Urban district, which includes Freetown, Western Area Rural district, and certain chiefdoms in Bombali, Port Loko, and Tonkolili districts. These study locations were selected because they have been heavily affected by the Ebola outbreak in the past few months.

“We are happy to be partnering with MoHS and CDC on this important study, which may help to prevent future cases of Ebola,” said Mohamed Samai, M.B., Ch.B., Ph.D., acting Provost of COMAHS and the study’s principal investigator. “It brings me hope and pride that my country can take from this devastating epidemic something that may benefit people around the world.”

When participants enroll in the study, they will be assigned randomly to one of two timeframes for vaccination – either immediately or about six months later. All study participants will receive the vaccine and be followed closely for six months. The study will evaluate if and how well the vaccine worked by comparing rates of Ebola virus disease in those who are vaccinated to those who have not yet received the vaccine.

AN END TO BED SORES? VA SAYS DEVICE BEING TESTED

FROM:  U.S. DEPARTMENT OF VETERANS AFFAIRS
Groundbreaking Device Being Tested By VA May Put End to Pressure Ulcers
March 19, 2015, 10:23:00 AM
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Groundbreaking Device Being Tested By VA May Put End to Pressure Ulcers
 Helps detect the earliest signs of ulcer formation

Pressure ulcers (commonly known as bed sores) are one of the most troublesome and painful complications for patients during a long hospital stay, but a joint project between the Department of Veterans Affairs (VA) Center for Innovation and General Electric (GE) Global Research may one day make pressure ulcers a thing of the past.

A multi-disciplinary team of scientists have combined an array of sensing and analytical tools, including motion analysis, thermal profiling, image classification/segmentation, 3-D object reconstruction and vapor detection into a single medical sensing handheld probe to assess and monitor the progression of bed sores or pressure ulcers.

The device is currently in pilot testing at the Augusta, Georgia, VA Medical Center Spinal Cord Injury Unit. The probe integrates multiple sensing capabilities with analytics and user support features to more acutely measure pressure ulcer formation and/or to determine if an ulcer is healing.

“The collaboration with GE is another example of the innovative work VA is doing with our private sector colleagues to advance the science of health care for our Veterans,” said Dr. Carolyn Clancy, VA’s Interim Under Secretary for Health. “We are pleased to work with GE to pilot a technology that holds the promise of revolutionizing the protocol for preventing and treating painful bed sores. We know that if patients are not turned on a regular basis, they can develop bed sores during their hospital stay as pressure builds up on their skin. By combining physical inspection with the technology capable of allowing real-time monitoring, we may be able to prevent ulcers from forming or advancing. This innovation is about providing the best care to our Veterans and collaborations like this one with GE helps us do just that.”

Individuals with spinal cord injuries with loss of sensation and mobility are particularly at risk for developing pressure ulcers. In U.S. hospitals alone, an estimated 2.5 million patients per year develop pressure ulcers, which require treatment.

“Pressure ulcers are a very pervasive, but also very preventable condition for hospital patients,” said Ting Yu, GE’s Principal Investigator on the pressure ulcer prevention and care program. “The device can help detect the earliest signs of ulcer formation. It also provides a more objective and comprehensive assessment of the wound to understand its progression. We’re now testing this device with VA in a clinical setting to see if it provides the kind of information that will help hospitals reduce and one day eliminate pressure ulcers from developing with patients.”

NSF VIDEO: LIGHT-BASED VIRUS DETECTION – CES 2015

WHITE HOUSE FACT SHEET ON PRECISION MEDICINE INITIATIVE

FROM:  THE WHITE HOUSE   
January 30, 2015
FACT SHEET: President Obama’s Precision Medicine Initiative

Building on President Obama’s announcement in his State of the Union Address, today the Administration is unveiling details about the Precision Medicine Initiative, a bold new research effort to revolutionize how we improve health and treat disease.  Launched with a $215 million investment in the President’s 2016 Budget, the Precision Medicine Initiative will pioneer a new model of patient-powered research that promises to accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies to select which treatments will work best for which patients.

Most medical treatments have been designed for the “average patient.” As a result of this “one-size-fits-all-approach,” treatments can be very successful for some patients but not for others.  This is changing with the emergence of precision medicine, an innovative approach to disease prevention and treatment that takes into account individual differences in people’s genes, environments, and lifestyles.  Precision medicine gives clinicians tools to better understand the complex mechanisms underlying a patient’s health, disease, or condition, and to better predict which treatments will be most effective.

Advances in precision medicine have already led to powerful new discoveries and several new treatments that are tailored to specific characteristics of individuals, such as a person’s genetic makeup, or the genetic profile of an individual’s tumor.  This is leading to a transformation in the way we can treat diseases such as cancer.  Patients with breast, lung, and colorectal cancers, as well as melanomas and leukemias, for instance, routinely undergo molecular testing as part of patient care, enabling physicians to select treatments that improve chances of survival and reduce exposure to adverse effects.

The potential for precision medicine to improve care and speed the development of new treatments has only just begun to be tapped. Translating initial successes to a larger scale will require a coordinated and sustained national effort.  Through collaborative public and private efforts, the Precision Medicine Initiative will leverage advances in genomics, emerging methods for managing and analyzing large data sets while protecting privacy, and health information technology to accelerate biomedical discoveries.  The Initiative will also engage a million or more Americans to volunteer to contribute their health data to improve health outcomes, fuel the development of new treatments, and catalyze a new era of data-based and more precise medical treatment.

Key Investments to Launch the Precision Medicine Initiative:

Complementing robust investments to broadly support research, development, and innovation, the President’s 2016 Budget will provide a $215 million investment for the National Institutes of Health (NIH), together with the Food and Drug Administration (FDA), and the Office of the National Coordinator for Health Information Technology (ONC) to support this effort, including:

$130 million to NIH for development of a voluntary national research cohort of a million or more volunteers to propel our understanding of health and disease and set the foundation for a new way of doing research through engaged participants and open, responsible data sharing.

$70 million to the National Cancer Institute (NCI), part of NIH, to scale up efforts to identify genomic drivers in cancer and apply that knowledge in the development of more effective approaches to cancer treatment.

$10 million to FDA to acquire additional expertise and advance the development of high quality, curated databases to support the regulatory structure needed to advance innovation in precision medicine and protect public health.

$5 million to ONC to support the development of interoperability standards and requirements that address privacy and enable secure exchange of data across systems.

Objectives of the Precision Medicine Initiative:

More and better treatments for cancer: NCI will accelerate the design and testing of effective, tailored treatments for cancer by expanding genetically based clinical cancer trials, exploring fundamental aspects of cancer biology, and establishing a national “cancer knowledge network” that will generate and share new knowledge to fuel scientific discovery and guide treatment decisions.
Creation of a voluntary national research cohort: NIH, in collaboration with other agencies and stakeholders, will launch a national, patient-powered research cohort of one million or more Americans who volunteer to participate in research.  Participants will be involved in the design of the Initiative and will have the opportunity to contribute diverse sources of data—including medical records; profiles of the patient’s genes, metabolites (chemical makeup), and microorganisms in and on the body; environmental and lifestyle data; patient-generated information; and personal device and sensor data.  Privacy will be rigorously protected.  This ambitious project will leverage existing research and clinical networks and build on innovative research models that enable patients to be active participants and partners.  The cohort will be broadly accessible to qualified researchers and will have the potential to inspire scientists from multiple disciplines to join the effort and apply their creative thinking to generate new insights. The ONC will develop interoperability standards and requirements to ensure secure data exchange with patients’ consent, to empower patients and clinicians and advance individual, community, and population health.

Commitment to protecting privacy: To ensure from the start that this Initiative adheres to rigorous privacy protections, the White House will launch a multi-stakeholder process with HHS and other Federal agencies to solicit input from patient groups, bioethicists, privacy, and civil liberties advocates, technologists, and other experts in order to identify and address any legal and technical issues related to the privacy and security of data in the context of precision medicine.
Regulatory modernization: The Initiative will include reviewing the current regulatory landscape to determine whether changes are needed to support the development of this new research and care model, including its critical privacy and participant protection framework.  As part of this effort, the FDA will develop a new approach for evaluating Next Generation Sequencing technologies — tests that rapidly sequence large segments of a person’s DNA, or even their entire genome. The new approach will facilitate the generation of knowledge about which genetic changes are important to patient care and foster innovation in genetic sequencing technology, while ensuring that the tests are accurate and reliable.

Public-private partnerships: The Obama Administration will forge strong partnerships with existing research cohorts, patient groups, and the private sector to develop the infrastructure that will be needed to expand cancer genomics, and to launch a voluntary million-person cohort.  The Administration will call on academic medical centers, researchers, foundations, privacy experts, medical ethicists, and medical product innovators to lay the foundation for this effort, including developing new approaches to patient participation and empowerment.  The Administration will carefully consider and develop an approach to precision medicine, including appropriate regulatory frameworks, that ensures consumers have access to their own health data – and to the applications and services that can safely and accurately analyze it – so that in addition to treating disease, we can empower individuals and families to invest in and manage their health.

ENGINEER LOOKS AT DIABETES AND HEART DISEASE

FROM:  NATIONAL SCIENCE FOUNDATION 
Mechanical engineer studies flow of blood vessels related to diabetes and resulting heart disease
Research could lead to development of new drugs and tissue engineering applications

People with diabetes develop early and severe heart disease, specifically atherosclerosis, a condition in which plaque builds up inside the arteries. Alisa Clyne, a mechanical engineer by training, wants to better understand the biomechanics of this process.

"We know people with diabetes get these plaques but not why they are more severe with diabetes," says Clyne, an associate professor of mechanical engineering and mechanics at Drexel University. "Could there be a mechanical aspect to it?"

The National Science Foundation (NSF)-funded scientist specifically is studying the behavior of endothelial cells, which form the inner layer of blood vessels, and which "sense the mechanics of their environment and respond to it," she says. "They are exposed to a variety of mechanical forces, mostly from blood flow."

Moreover, blood flow, specifically shear stress--the force of flowing blood on the endothelial surfaces--cause the cells to react in multiple ways. "Atherosclerosis occurs in locations where there are disturbances in the blood flow," she says. "We want to know if the relationship between atherosclerotic plaque development and endothelial response to fluid flow is altered in diabetic conditions."

With normal flow, "your endothelial cells should not be dysfunctional, and you should not get plaque," she adds. "So the question for us is, if you change the endothelial cell environment to simulate a diabetic condition, such as high blood sugar, would there be a change in the way the cells are able to respond to fluid flow?"

Insights into the role of these cells in plaque development potentially could provide new ideas for drug development, as well as tissue engineering applications, such as designing new blood vessels.

"This information about how the cell mechanisms respond to blood flow is important," Clyne says. "For example, you could tissue engineer a better blood vessel for coronary artery bypass surgery by understanding how the endothelial cells respond to flow in a diabetic environment."

Clyne is conducting her research under an NSF Faculty Early Career Development (CAREER) award, which she received in 2009. The award supports junior faculty who exemplify the role of teacher-scholars through outstanding research, excellent education, and the integration of education and research within the context of the mission of their organization. NSF is funding her work with about $400,000 over five years.

Endothelial cells align and elongate in the direction of the shear stress, and change some of their functions as well. For example, in response to increased shear stress, endothelial cells produce more nitric oxide, a vasodilator which causes the blood vessels to expand. This physiological response decreases blood velocity and thereby reduces shear stress down to the original level. Nitric oxide also scavenges reactive oxygen species and reduces inflammation, both of which are factors that contribute to atherosclerotic plaque development. If endothelial cells do not produce nitric oxide in response to shear stress in a diabetic environment, this could contribute to atherosclerosis in people with diabetes.

In her experiments, Clyne cultures endothelial cells in a parallel plate flow chamber, which allows her to put "flow" over the cells to simulate the stresses they would experience in the human body. "We added high sugar levels to see how the cells would respond in normal flow," she says.

"One thing high sugars do is change the structure of proteins," she explains. "There are proteins underneath the endothelial cells, and the cells attach to them. The one we study in particular is collagen. As we age, or if you have high sugar levels, the collagen becomes glycated, meaning that sugar attaches to one of the collagen amino acids. When the cells are attached to glycated collagen, rather than normal collagen, it changes how they respond to fluid flow. "

The researchers measured the responses, including the release of nitric oxide, and found that the cells "don't align in the flow direction or release nitric oxide when they are on glycated collagen," she says. " The way in which cells adhere to the substrate proteins changes many signaling pathways in the cells. Our cells adhere to glycated collagen in a different way from native collagen, and this changes the way that they are able to respond to mechanical forces from fluid flow."

The researchers also looked at the effects of increasing sugar levels in the cultured cells and found that high sugar levels--and low sugar levels--also changed the way the cells respond to fluid flow. "So if you are at either extreme, you're in trouble," she says. "Sugar can either directly affect the cells or affect the proteins the cells adhere to, so it has two effects."

As part of the CAREER educational component, Clyne's lab is conducting an outreach program with the Girl Scouts, including a "Science Saturdays" program at Drexel, bringing in junior high school-age scouts for up to six Saturdays to teach them about different kinds of engineering, and how engineering applications can solve human health problems. The scouts are paired with mentors, who are Drexel engineering undergraduate students.

They engage in hands-on activities that relate to engineering. For example, they constructed robot cars (mechanical engineering), made lip gloss (chemical engineering) and participated in a water filtration project (civil engineering).

"Over the course of the program, they also worked on a design project related to biomedical engineering. One year, the girls created solutions that would help soldiers coming home from the war without a limb," she says. "One group made a gripper hand to help with eating, whereas another group made a device to improve balance using a prosthetic leg. The girls learned about how engineering contributes to helping others, which hopefully will encourage them to consider engineering careers."

-- Marlene Cimons, National Science Foundation
Investigators
Alisa Morss Clyne

NSF DISCUSSES THE FUTURE OF TRANSDERMAL ULTRASOUND DELIVERY OF MEDICATIONS

FROM:  NATIONAL SCIENCE FOUNDATION 
'Smuggling' drugs at the cellular level
Drexel researchers use ultrasound to deliver customized medication through the skin
December 5, 2013

Medicated adhesive patches have become a preferred method of delivery for everything from nicotine to hormones to motion sickness medication.

Drexel University researchers are trying to expand the possibilities of this system--called transdermal delivery--with the help of a cleverly designed delivery vehicle and an ultrasonic "push," or pressure from sound waves.

The advantage of transdermal drug delivery is the ability to regulate the release of medication into the bloodstream and promote a more direct interaction of the treatment with the affected area. But the challenge of this method is that the skin is very good at protecting the body from invaders--even the helpful kind.

Molecules of nicotine and medication currently delivered via adhesive patch are small enough to pass through the pores. To sneak a slightly larger package--say, insulin or arthritis medication--past the body's epidermal defenses requires a bit more biological trickery.

Steven P. Wrenn, of Drexel's College of Engineering, and Peter A. Lewin, from Drexel's School of Biomedical Engineering, Science and Health Systems, are driving forces behind this research. Their team is investigating the molecular architecture of human skin and certain promising drugs and compounds, as well as the mechanics of an ultrasound interface necessary to broaden the capabilities of transdermal drug delivery.

Their work is part of a larger trend: More and more, researchers are exploring advanced materials and manufacturing techniques for biomedical applications. New, high-precision technologies and more rapid, personalized fabrication methods allow engineers to design on smaller scales, such as those required to traverse the human body.

The package

The Drexel team is looking at a drug called Methotrexate (MTX) as an example of the cargo that could one day be transported into the body using an ultrasound "Band-Aid." MTX is used to treat arthritis and various types of cancer. It is typically taken orally, but after prolonged use it can become toxic to the liver. This side effect could be avoided if the drug were delivered transdermally, as afflicted cells would use up much of the medication before it could reach the liver.

It's not an ideal candidate for topical application, however, because its molecules are too large to easily pass through the pores of the skin. It is also easily dissolved in water, which means that, to be effective, it must be contained and protected until it reaches its destination.

The carrier

Wrenn's group is designing a vessel that can transport the medicine and penetrate the skin's first line of defense: the stratum corneum. This barrier is the body's equivalent of a brick wall built with dead skin cell bricks and a lipid mortar.

The group selected the liposome, a fabricated lipid sac filled with water, as the carrier. Liposomes are prime candidates for the job because they are made of the same lipid substrate as the stratum corneum's "mortar," so they can pass through the skin virtually unnoticed.

The team is also engineering the sacs so they're hearty enough to survive a transdermal push, but capable of being opened to release the medicine once inside the body.

The push and the pop

After coaxing the liposomes through the epidermis, the tunable ultrasound patch would "pop" them open to deliver the medicine.

But this interaction is where the real problem lies. The liposome, while a perfect craft for making a stealthy, transdermal entry is not rugged enough to withstand the intensity of ultrasound required to push it through the skin.

Wrenn's group devised a creative solution to this quandary by adding a bit of ballast to the liposome vessel, in the form of tiny gas-filled sacs called microbubbles.

Microbubbles respond to ultrasound in two ways that are key to making the liposome's transdermal voyage a success. First, they can be pushed by ultrasound at an intensity gentle enough to keep the liposome intact. So, nesting the microbubbles inside a liposome is analogous to raising the sail on a boat to catch the wind.

Secondly, when the intensity of the ultrasound is turned up a bit, it causes microbubbles to wobble like a spring and--if the intensity is high enough--pop. Wrenn's group has shown that these gas implosions in the vicinity of the liposome can rip it open, thus allowing disbursal of its contents.

A significant advantage of their approach over current transdermal delivery methods is that it could easily be customized to work for a broad array of drugs and other biological products.

The future

By combining these findings, the team suggests that a liposome laden with a payload of medicine and using microbubbles to sail an ultrasonic "wind" should be able to traverse the epidermis and enter the body. An adjustment to the ultrasound frequency could then pop the microbubbles and split open the liposome to release the medicine.

With a hefty amount of research on liposome architecture underway, the next step for the group will be to fine-tune the ultrasound patch delivery system and work toward a successful transdermal push.

Editor's Note: This Behind the Scenes article was first provided to LiveScience in partnership with the National Science Foundation.

-- Britt Faulstick, Drexel University

MULTI-INSTITUTIONAL CONSORTIA ESTABLISHED TO RESEARCH PTSD AND TBI

FROM:  U.S. DEPARTMENT OF DEFENSE 

DoD, VA Establish Two Multi-Institutional Consortia to Research PTSD and TBI

           In response to President Obama's Executive Order, the Departments of Defense (DoD) and Veterans Affairs (VA) highlighted today the establishment of two joint research consortia, at a combined investment of $107 million to research the diagnosis and treatment of post-traumatic stress disorder (PTSD) and mild traumatic brain injury (mTBI) over a five-year period.

           "VA is proud to join with its partners in the federal government and the academic community to support the President's vision and invest in research that could lead to innovative, new treatments for TBI and PTSD," said Secretary of Veterans Affairs Eric K. Shinseki. "We must do all we can to deliver the high-quality care our Service members and Veterans have earned and deserve."

           The Consortium to Alleviate PTSD (CAP), a collaborative effort between the University of Texas Health Science Center – San Antonio, San Antonio Military Medical Center, and the Boston VA Medical Center will attempt to develop the most effective diagnostic, prognostic, novel treatment, and rehabilitative strategies to treat acute PTSD and prevent chronic PTSD.

           The Chronic Effects of Neurotrauma Consortium (CENC), a collaborative effort between Virginia Commonwealth University, the Uniformed Services University of the Health Sciences, and the Richmond VA Medical Center will examine the factors which influence the chronic effects of mTBI and common comorbidities in order to improve diagnostic and treatment options.  A key point will be to further the understanding of the relationship between mTBI and neurodegenerative disease.

           Since Sep. 11, 2001, more than 2.5 million American service members have been deployed to Iraq and Afghanistan. Military service exposes service members to a variety of stressors, including risk to life, exposure to death, injury, sustained threat of injury, and the day-to-day family stress inherent in all phases of the military life cycle.

           To improve prevention, diagnosis, and treatment of mental health conditions, the President released an Executive Order directing the Federal agencies to develop a coordinated National Research Action Plan. The Department of Defense (DoD), Department of Veterans Affairs (VA), the Department of Health and Human Services (HHS), and the Department of Education (ED) came forward with a wide-reaching plan to improve scientific understanding, effective treatment,  and reduce occurrences of Post-Traumatic Stress Disorder (PTSD), Traumatic Brain Injury (TBI), co-occurring conditions, and suicide.