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Wearable Sensor Promises More Efficient Early Cancer Drug Development

Posted on by Lawrence Tabak, D.D.S., Ph.D.

A labeled sensor rests on the surface of the skin. Under the sensor, beneath the skin in a tumor. A graph shows the tumor's size over time.

Wearable electronic sensors hold tremendous promise for improving human health and wellness. That promise already runs the gamut from real-time monitoring of blood pressure and abnormal heart rhythms to measuring alcohol consumption and even administering vaccines.

Now a new study published in the journal Science Advances [1] demonstrates the promise of wearables also extends to the laboratory. A team of engineers has developed a flexible, adhesive strip that, at first glance, looks like a Band-Aid. But this “bandage” actually contains an ultra-sensitive, battery-operated sensor that’s activated when placed on the skin of mouse models used to study possible new cancer drugs.

This sensor is so sensitive that it can detect, in real time, changes in the size of a tumor down to one-hundredth of a millimeter. That’s about the thickness of the plastic cling wrap you likely have in your kitchen! The device beams those measures to a smartphone app, capturing changes in tumor growth minute by minute over time.

The goal is to determine much sooner—and with greater automation and precision—which potential drug candidates undergoing early testing in the lab best inhibit tumor growth and, consequently, should be studied further. In their studies in mouse models of cancer, researchers found the new sensor could detect differences between tumors treated with an active drug and those treated with a placebo within five hours. Those quick results also were validated using more traditional methods to confirm their accuracy.

The device is the work of a team led by Alex Abramson, a former post-doc with Zhenan Bao, Stanford University’s School of Engineering, Palo Alto, CA. Abramson has since launched his own lab at the Georgia Institute of Technology, Atlanta.

The Stanford team began looking for a technological solution after realizing the early testing of potential cancer drugs typically requires researchers to make tricky measurements using pincer-like calipers by hand. Not only is the process tedious and slow, it’s less than an ideal way to capture changes in soft tissues with the desired precision. The imprecision can also lead to false leads that won’t pan out further along in the drug development pipeline, at great time and expense to their developers.

To refine the process, the NIH-supported team turned to wearable technology and recent advances in flexible electronic materials. They developed a device dubbed FAST (short for Flexible Autonomous Sensor measuring Tumors). Its sensor, embedded in a skin patch, is composed of a flexible and stretchable, skin-like polymer with embedded gold circuitry.

Here’s how FAST works: Coated on top of the polymer skin patch is a layer of gold. When stretched, it forms small cracks that change the material’s electrical conductivity. As the material stretches, even slightly, the number of cracks increases, causing the electronic resistance in the sensor to increase as well. As the material contracts, any cracks come back together, and conductivity improves.

By picking up on those changes in conductivity, the device measures precisely the strain on the polymer membrane—an indication of whether the tumor underneath is stable, growing, or shrinking—and transmits that data to a smartphone. Based on that information, potential therapies that are linked to rapid tumor shrinkage can be fast-tracked for further study while those that allow a tumor to continue growing can be cast aside.

The researchers are continuing to test their sensor in more cancer models and with more therapies to extend these initial findings. Already, they have identified at least three significant advantages of their device in early cancer drug testing:

• FAST is non-invasive and captures precise measurements on its own.
• It can provide continuous monitoring, for weeks, months, or over the course of study.
• The flexible sensor fully surrounds the tumor and can therefore detect 3D changes in shape that would be hard to pick up otherwise in real-time with existing technologies.

By now, you are probably asking yourself: Could FAST also be applied as a wearable for cancer patients to monitor in real-time whether an approved chemotherapy regimen is working? It is too early to say. So far, FAST has not been tested in people. But, as highlighted in this paper, FAST is off to, well, a fast start and points to the vast potential of wearables in human health, wellness, and also in the lab.

Reference:

[1] A flexible electronic strain sensor for the real-time monitoring of tumor regression. Abramson A, Chan CT, Khan Y, Mermin-Bunnell A, Matsuhisa N, Fong R, Shad R, Hiesinger W, Mallick P, Gambhir SS, Bao Z. Sci Adv. 2022 Sep 16;8(37):eabn6550.

Links:

Stanford Wearable Electronics Initiative (Stanford University, Palo Alto, CA)

Bao Group (Stanford University)

Abramson Lab (Georgia Institute of Technology, Atlanta)

NIH Support: National Institute of Biomedical Imaging and Bioengineering


Tackling Complex Scientific Questions Requires a Team Approach

Posted on by Nora D. Volkow, M.D., National Institute on Drug Abuse

A group of people are hand in hand in a spiral. Team Science
Credit: Getty Images/melitas

During the COVID-19 pandemic, we have seen unprecedented, rapid scientific collaboration, as experts around the world in discrete, previously disconnected fields, have found ways to collaborate to face a common cause. For example, physicists helped respiratory specialists understand how virus particles could spread in air, leading to improved mitigation strategies. Specialists in cardiovascular science, neuroscience, immunology, and other fields are now working together to understand and address Long COVID. Over the past two years, we have also seen remarkable international sharing of epidemiological data and information on effects of vaccines.

Science is increasingly a team activity, which is true for many fields, not just biomedicine. The professional diversity of research teams reflects the increased complexity of the questions science is called upon to answer. This is especially obvious in the study of the brain, which is the most complex system known to us.

The NIH’s Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative, with the goal of vastly enhancing neuroscience through new technologies, includes research teams with neuroscientists, engineers, mathematicians, physicists, data scientists, ethicists, and more. Nearly half (47 percent) of grant awards have multiple principal investigators.

Besides the BRAIN Initiative, other multi-institute NIH research projects are applying team science to complex research questions, such as those related to neurodevelopment, addiction, and pain. The Helping to End Addiction Long-term® Initiative, or NIH HEAL Initiative®, created a team-based research framework to advance promising pain therapeutics quickly to clinical testing.

In the Adolescent Brain Cognitive Development (ABCD) study, which is led by NIDA in close partnership with NIH’s National Institute on Alcohol Abuse and Alcoholism (NIAAA), and other NIH institutes, 21 research centers are collecting behavioral, biospecimen, and neuroimaging data from 11,878 children from age 10 through their teens. Teams led by experts in adolescent psychiatry, developmental psychology, and pediatrics interview participants and their families. These experts then gather a battery of health metrics from psychological, cognitive, sociocultural, and physical assessments, including collection and analysis of various kinds of biospecimens (blood, saliva). Further, experts in biophysics gather information on the structure and function of participants’ brains every two years.

A similar study of young children in the first decade of life beginning with the prenatal period, the HEALthy Brain and Child Development (HBCD) study, supported by HEAL, NIDA, and several other NIH institutes and centers, is now underway at 25 research sites across the country. A range of scientific specialists, similar to that in the ABCD study, is involved in this effort. In this case, they are aided by experts in obstetric care and in infant neuroimaging.

For both of these studies, teams of data scientists validate and curate all the information generated and make it available to researchers across the world. This makes it possible to investigate complex questions such as human neurodevelopmental diversity and the effects of genes and social experiences and their relation to mental health. More than half of the publications using ABCD data have been authored by non-ABCD investigators taking advantage of the open-access format.

Yet, institutions that conduct and fund science—including NIH—have been slow to support and reward collaboration. Because authorship and funding are so important in tenure and promotion decisions at universities, for example, an individual’s contribution to larger, multi-investigator projects on which they may not be the grantee or lead author on a study publication may carry less weight.

For this reason, early-career scientists may be particularly reluctant to collaborate on team projects. Among the recommendations of a 2015 National Academies of Sciences, Engineering, and Medicine (NASEM) report, Enhancing the Effectiveness of Team Science, was that universities and other institutions should find effective ways to give credit for team-based work to assist promotion and tenure committees.

The strongest teams will be diverse in other respects, not just scientific expertise. Besides more actively fostering productive collaborations across disciplines, NIH is making a more concerted effort to promote racial equity and inclusivity in our research workforce, both through the NIH UNITE Initiative and through Institute-specific initiatives like NIDA’s Racial Equity Initiative.

To promote diversity, inclusivity, and accessibility in research, the BRAIN Initiative recently added a requirement in most of its funding opportunity announcements (FOAs) that has applicants include a Plan for Enhancing Diverse Perspectives (PEDP) in the proposed research. The PEDPs are evaluated and scored during the peer review as part of the holistic considerations used to inform funding decisions. These long-overdue measures will not only ensure that NIH-funded science is more diverse, but they are also important steps toward studying and addressing social determinants of health and the health disparities that exist for so many conditions.

Increasingly, scientific discovery is as much about exploring new connections between different kinds of researchers as it is about finding new relationships among different kinds of scientific databases. The challenges before us are great—ending the COVID pandemic, finding a solution to the addiction and overdose crisis, and so many others—and increased collaboration between scientists will give us the greatest chance to successfully overcome these challenges.

Links:

Nora Volkow’s Blog (National Institute on Drug Abuse/NIH)

Adolescent Brain Cognitive Development Study

Brain Research Through Advancing Innovative Neurotechnologies® (BRAIN) Initiative (NIH)

Racial Equity Initiative (NIDA)

Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 13th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.


Using Science To Solve Oral Health Inequities

Posted on by Rena D'Souza, D.D.S., M.S., Ph.D., National Institute of Dental and Craniofacial Research

A grid of smiling people intermixed with dental health images

At NIH, we have a front row seat to remarkable advances in science and technology that help Americans live longer, healthier lives. By studying the role that the mouth and saliva can play in the transmission and prevention of disease, the National Institute of Dental and Craniofacial Research (NIDCR) contributed to our understanding of infectious agents like the coronavirus SARS-CoV-2, the cause of COVID-19. While these and other NIH-supported advances undoubtedly can improve our nation’s health as a whole, not everyone enjoys the benefits equally—or at all. As a result, people’s health, including their oral health, suffers.

That’s a major takeaway from Oral Health in America: Advances and Challenges, a report that NIDCR recently released on the status of the nation’s oral health over the last 20 years. The report shows that oral health has improved in some ways, but people from marginalized groups —such as those experiencing poverty, people from racial and ethnic minority groups, the frail elderly, and immigrants—shoulder an unequal burden of oral disease.

At NIDCR, we are taking the lessons learned from the Oral Health in America report and using them to inform our research. It will help us to discover ways to eliminate these oral health differences, or disparities, so that everyone can enjoy the benefits of good oral health.

Why does oral health matter? It is essential for our overall health, well-being, and productivity. Untreated oral diseases, such as tooth decay and gum disease, can cause infections, pain, and tooth loss, which affect the ability to chew, swallow, eat a balanced diet, speak, smile, and go to school and work.

Treatments to fix these problems are expensive, so people of low socioeconomic means are less likely to receive quality care in a timely manner. Importantly, untreated gum disease is associated with serous systemic conditions such as diabetes, heart disease, and Alzheimer’s disease.

A person experiencing poverty also may be at increased risk for mental illness. That, in turn, can make it hard to practice oral hygiene, such as toothbrushing and flossing, or to maintain a relationship with a dental provider. Mental illnesses and substance use disorders often go hand-in-hand, and overuse of opioids, alcohol, and tobacco products also can raise the risk for tooth decay, gum disease, and oral cancers. Untreated dental diseases in this setting can cause pain, sometimes leading to increased substance use as a means of self-medication.

Research to understand better the connections between mental health, addiction, and oral health, particularly as they relate to health disparities, can help us develop more effective ways to treat patients. It also will help us prepare health providers, including dentists, to deliver the right kind of care to patients.

Another area that is ripe for investigation is to find ways to make it easier for people to get dental care, especially those from marginalized or rural communities. For example, the COVID-19 pandemic spurred more dentists to use teledentistry, where practitioners meet with patients remotely as a way to provide certain aspects of care, such as consultations, oral health screenings, treatment planning, and education.

Teledentistry holds promise as a cost-saving approach to connect dentists to people living in regions that may have a shortage of dentists. Some evidence suggests that providing access to oral health care outside of dental clinics—such as in schools, primary care offices, and community centers—has helped reduce oral health disparities in children. We need additional research to find out if this type of approach also might reduce disparities in adults.

These are just some of the opportunities highlighted in the Oral Health in America report that will inform NIDCR’s research in the coming years. Just as science, innovation, and new technologies have helped solve some of the most challenging health problems of our time, so too can they lead us to solutions for tackling oral health disparities. Our job will not be done until we can improve oral and overall health for everyone across America.

Links:

Oral Health in America: Advances and Challenges (National Institute of Dental and Craniofacial Research/NIH)

Oral Health in America Editors Issue Guidance for Improving Oral Health for All (NIDCR)

NIH, HHS Leaders Call for Research and Policy Changes To Address Oral Health Inequities (NIDCR)

NIH/NIDCR Releases Oral Health in America: Advances and Challenges (NIDCR)

Note: Acting NIH Director Lawrence Tabak has asked the heads of NIH’s Institutes and Centers (ICs) to contribute occasional guest posts to the blog to highlight some of the interesting science that they support and conduct. This is the 11th in the series of NIH IC guest posts that will run until a new permanent NIH director is in place.


How Severe COVID-19 Can Tragically Lead to Lung Failure and Death

Posted on by Dr. Francis Collins

SARS-CoV-2 and a sick woman. Leader lines label lungs, liver, heart and kidney

More than 3 million people around the world, now tragically including thousands every day in India, have lost their lives to severe COVID-19. Though incredible progress has been made in a little more than a year to develop effective vaccines, diagnostic tests, and treatments, there’s still much we don’t know about what precisely happens in the lungs and other parts of the body that leads to lethal outcomes.

Two recent studies in the journal Nature provide some of the most-detailed analyses yet about the effects on the human body of SARS-CoV-2, the coronavirus that causes COVID-19 [1,2]. The research shows that in people with advanced infections, SARS-CoV-2 often unleashes a devastating series of host events in the lungs prior to death. These events include runaway inflammation and rampant tissue destruction that the lungs cannot repair.

Both studies were supported by NIH. One comes from a team led by Benjamin Izar, Columbia University, New York. The other involves a group led by Aviv Regev, now at Genentech, and formerly at Broad Institute of MIT and Harvard, Cambridge, MA.

Each team analyzed samples of essential tissues gathered from COVID-19 patients shortly after their deaths. Izar’s team set up a rapid autopsy program to collect and freeze samples within hours of death. He and his team performed single-cell RNA sequencing on about 116,000 cells from the lung tissue of 19 men and women. Similarly, Regev’s team developed an autopsy biobank that included 420 total samples from 11 organ systems, which were used to generate multiple single-cell atlases of tissues from the lung, kidney, liver, and heart.

Izar’s team found that the lungs of people who died of COVID-19 were filled with immune cells called macrophages. While macrophages normally help to fight an infectious virus, they seemed in this case to produce a vicious cycle of severe inflammation that further damaged lung tissue. The researchers also discovered that the macrophages produced high levels of IL-1β, a type of small inflammatory protein called a cytokine. This suggests that drugs to reduce effects of IL-1β might have promise to control lung inflammation in the sickest patients.

As a person clears and recovers from a typical respiratory infection, such as the flu, the lung repairs the damage. But in severe COVID-19, both studies suggest this isn’t always possible. Not only does SARS-CoV-2 destroy cells within air sacs, called alveoli, that are essential for the exchange of oxygen and carbon dioxide, but the unchecked inflammation apparently also impairs remaining cells from repairing the damage. In fact, the lungs’ regenerative cells are suspended in a kind of reparative limbo, unable to complete the last steps needed to replace healthy alveolar tissue.

In both studies, the lung tissue also contained an unusually large number of fibroblast cells. Izar’s team went a step further to show increased numbers of a specific type of pathological fibroblast, which likely drives the rapid lung scarring (pulmonary fibrosis) seen in severe COVID-19. The findings point to specific fibroblast proteins that may serve as drug targets to block deleterious effects.

Regev’s team also describes how the virus affects other parts of the body. One surprising discovery was there was scant evidence of direct SARS-CoV-2 infection in the liver, kidney, or heart tissue of the deceased. Yet, a closer look heart tissue revealed widespread damage, documenting that many different coronary cell types had altered their genetic programs. It’s still to be determined if that’s because the virus had already been cleared from the heart prior to death. Alternatively, the heart damage might not be caused directly by SARS-CoV-2, and may arise from secondary immune and/or metabolic disruptions.

Together, these two studies provide clearer pictures of the pathology in the most severe and lethal cases of COVID-19. The data from these cell atlases has been made freely available for other researchers around the world to explore and analyze. The hope is that these vast data sets, together with future analyses and studies of people who’ve tragically lost their lives to this pandemic, will improve our understanding of long-term complications in patients who’ve survived. They also will now serve as an important foundational resource for the development of promising therapies, with the goal of preventing future complications and deaths due to COVID-19.

References:

[1] A molecular single-cell lung atlas of lethal COVID-19. Melms JC, Biermann J, Huang H, Wang Y, Nair A, Tagore S, Katsyv I, Rendeiro AF, Amin AD, Schapiro D, Frangieh CJ, Luoma AM, Filliol A, Fang Y, Ravichandran H, Clausi MG, Alba GA, Rogava M, Chen SW, Ho P, Montoro DT, Kornberg AE, Han AS, Bakhoum MF, Anandasabapathy N, Suárez-Fariñas M, Bakhoum SF, Bram Y, Borczuk A, Guo XV, Lefkowitch JH, Marboe C, Lagana SM, Del Portillo A, Zorn E, Markowitz GS, Schwabe RF, Schwartz RE, Elemento O, Saqi A, Hibshoosh H, Que J, Izar B. Nature. 2021 Apr 29.

[2] COVID-19 tissue atlases reveal SARS-CoV-2 pathology and cellular targets. Delorey TM, Ziegler CGK, Heimberg G, Normand R, Shalek AK, Villani AC, Rozenblatt-Rosen O, Regev A. et al. Nature. 2021 Apr 29.

Links:

COVID-19 Research (NIH)

Izar Lab (Columbia University, New York)

Aviv Regev (Genentech, South San Francisco, CA)

NIH Support: National Center for Advancing Translational Sciences; National Heart, Lung, and Blood Institute; National Cancer Institute; National Institute of Allergy and Infectious Diseases; National Institute of Diabetes and Digestive and Kidney Diseases; National Human Genome Research Institute; National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism


Lessons Learned About Substance Use Disorders During the COVID-19 Pandemic

Posted on by Dr. Francis Collins

Nora Volkow and Francis Collins in a teleconference from their recent conversation

Every spring, I and my colleague Dr. Nora Volkow, Director of NIH’s National Institute on Drug Abuse (NIDA), join with leaders across the country in the Rx Drug Abuse and Heroin Summit. Our role is to discuss NIH’s continued progress in tackling our nation’s opioid crisis. Because of the continued threat of COVID-19 pandemic, we joined in virtually for the second year in a row.

While the demands of the pandemic have been challenging for everyone, biomedical researchers have remained hard at work to address the opioid crisis. Among the many ways that NIH is supporting these efforts is through its Helping to End Addiction Long-Term (HEAL) Initiative, which is directing more than $1.5 billion to researchers and communities across the country.

Here’s a condensed transcript of our April 6th video dialogue, which focused on the impact of the COVID-19 pandemic on people struggling with substance use disorders and those who are trying to help them.

HEAL NIH Helping to End Addition Long-term

Collins: What have we learned so far through HEAL? Well, one thing HEAL is doing is tackling the need for pain treatments that help people avoid the risks of opioids. This research has uncovered new targets and therapeutics for different types of pain, including neuropathic, post-surgical, osteoarthritic, and chemotherapy induced. We’re testing implanted devices, such as electrodes and non-invasive nerve stimulation; and looking at complementary and integrative approaches, such as phone-based physical therapy for low back pain.

Through HEAL, we’ve launched a first-in-human test of a vaccine to protect against the harmful effects of opioids, including relapse and overdose. We’re also testing a tool that provides pharmacists with a validated opioid use disorder risk measure. The goal is to identify better who’s at high risk for opioid addiction and to determine what kind of early intervention could be put in place.

Despite COVID, many clinical studies are now recruiting participants. This includes family-based prevention programs, culturally tailored interventions for hard-hit American Indian populations, and interventions that address social inequities, such as lack of housing.

We are also making progress on the truly heart-breaking problem of babies born dependent on opioids. HEAL has launched a study to test the effectiveness of a new approach to care that measures the severity of a baby’s withdrawal, based on their ability to eat, sleep, and be consoled. This approach helps provide appropriate treatment for these infants, without the use of medication when possible. We’re also developing novel technologies to help treat neonatal opioid withdrawal syndrome, including a gently vibrating hospital bassinet pad that’s received breakthrough device designation from the FDA.

2020 was an extraordinary year that was tragic in so many ways, including lives lost and economic disasters that have fallen upon families. The resilience and ingenuity of the scientific community has been impressive. Quick pivoting has resulted in some gains through research, maybe you could even call them silver linings in the midst of this terrible storm.

Nora, what’s been at the forefront of your mind as we’ve watched things unfold?

Volkow: When we did this one year ago, we didn’t know what to expect. Obviously, we were concerned that the stressors associated with a pandemic, with unknowns, are factors that have been recognized for many years to increase drug use. Unfortunately, what we’ve seen is an increase in drug use of all types across the country.

We have seen an exacerbation of the opioid epidemic, as evidenced by the number of people who have died. Already, in the 12 months ending in July 2020, there was a 24 percent increase in mortality from overdoses. Within those numbers, there was close to a 50 percent increase in mortality associated with fentanyl. We’re also seeing an increase, not just in deaths from fentanyl and other synthetic opioids, but in deaths from stimulant drugs, like cocaine and methamphetamine. And the largest increases have been very much driven by drug combinations.

So, we have the perfect storm. We have people stressed to their limits by decreases in the economy, the loss of jobs, the death of loved ones. On the other hand, we see dealers taking the opportunity to bring in drugs such as synthetic opioids and synthetic stimulants and distribute them to a much wider extent than previously seen.

Collins: On top of that, people are at risk of getting sick from COVID-19. What have we learned about the risks of coronavirus illness for people who use drugs?

Volkow: It is a double whammy. When you look at the electronic health records about the outcomes of people diagnosed with substance use disorders, you consistently see an increased risk for getting infected with COVID-19. And if you look at those who get infected, you observe a significantly increased risk of dying from COVID.

What’s driving this vulnerability? One factor is the pharmacological effects of these drugs. Basically, all of the drugs of abuse that result in addiction, notably opioids, damage the cardiopulmonary system. Some also damage the immune system. And we know that individuals who have any disruption of cardiovascular health, pulmonary health, immune function, or metabolism are at higher risk of getting infected with COVID-19 and having adverse outcomes.

But there’s another factor that’s as important—one that’s very tractable. It is the way in which our society has dealt with substance use disorders: not actually treating them as a disease that requires intervention and support for recovery. The stigmatization of individuals with addiction, the lack of access to treatment, the social isolation, have all created havoc by making these individuals so much more vulnerable to get infected with COVID-19.

They will not go to a doctor. They don’t want to be stigmatized. They need to go out into the streets to get access to the drugs. Many times, they don’t have a choice of what drugs to take because they cannot afford anything except what’s offered to them. So, many, especially those who are minorities, end up homeless or in jails or prison. Even before COVID, we knew that prisons and jails are places where infections can transmit extraordinary rapidly. You could see this was going to result in very negative outcomes for this group of individuals.

Collins: Nora, tell us more about the trends contributing to the current crisis. Maybe three or four years ago, what was going straight up was opioid use, especially heroin. Then, fentanyl started coming up very fast and that has continued. Now, we are seeing more stimulants and mixing of different types of drugs. What is the basis for this?

Volkow: At the beginning of the opiate pandemic, mortality was mainly associated with white Americans, many in rural or semi-suburban areas of the Appalachian states and in New Mexico and Arizona. That has shifted. The highest increase in mortality from opioids, predominantly driven by fentanyl, is now among Black Americans. They’ve had very, very high rates of mortality during the COVID pandemic. And when you look at mortality from methamphetamine, it’s chilling to realize that the risk of dying from methamphetamine overdose is 12-fold higher among American Indians and Alaskan Natives than other groups. This should make us pause to think about what’s driving these terrible racial disparities.

As for drug combinations, many deaths from methamphetamine or cocaine—an estimated 50 percent—are linked to these stimulant drugs being combined with fentanyl or heroin. Dealers are lacing these non-opioid drugs with cheaper, yet potent, opioids to make a larger profit. Someone who’s addicted to a stimulant drug like cocaine or methamphetamine is not tolerant to opioids, which means they are going to be at high risk of overdose if they get a stimulant drug that’s laced with an opioid like fentanyl. That’s been contributing to the sharp rise in mortality from non-opioid drugs.

Collins: I’m glad you raised the issue of health disparities. 2020 will go down as a year in which our nation had to focus on three public health crises at once. The first is the crisis of opioid use disorder and rising mortality from use of other drugs. The second is COVID-19. And the third is the realization, although the problem has been there all along, that health disparities continue to shorten the lives of far too many people.

The latter crisis has little to do with biology, but everything to do with the way in which our society still is afflicted by structural racism. We at NIH are looking at this circumstance, realizing that our own health disparities research agenda needs to be rethought. We have not fully incorporated all the factors that play out in health inequities and racial inequities in our country.

coronavirus icons

You were also talking about how stimulants have become more widespread. What about treatments for people with stimulant use disorders?

Volkow: For opioid addiction, we’re lucky because we have very effective medications: methadone, buprenorphine, naltrexone. On top of that, we have naloxone, Narcan, that if administered on time, can save the life of a person who has overdosed.

We don’t have any FDA-approved medication for methamphetamine addiction, and we don’t have any overdose reversal for methamphetamine. At the beginning of this year, we funded a large clinical trial aimed at investigating the benefits of the combination of two medications that were already approved as anti-depressants and for the treatment of smoking cessation and alcoholism. It found this combination significantly inhibits the urge to take drugs and therefore helps people stay away from use of methamphetamine. Now, we want to replicate these findings, and to tie that replication study in with guidelines from the FDA on what is needed to approve our new indication for these medications. Why? Because then insurance can cover it, and that will increase the likelihood that people will get treated.

Another exciting possibility is a monoclonal antibody against methamphetamine that’s in Phase 2 clinical trials. If someone comes into the emergency room with an overdose of a combination of opioid and methamphetamine, naloxone often will not work. But this monoclonal antibody with naloxone may offer a greater likelihood of success.
Another thing that’s promising is that investigators have been able to modify monoclonal antibodies so they stay in the bloodstream for a longer time. That means we may someday be able to use this passive immunization approach as a treatment for methamphetamine addiction.

Collins: That’s good to hear. Speaking of progress, is there any you want to point to within HEAL?

Volkow: There’s a lot of excitement surrounding medication development. We’re interested in developing antidotes that will be more effective in reversing overdose deaths from fentanyl. We’re also interested in providing longer lasting medications for treatment of opioid use disorders, which would improve the likelihood of patients being protected from overdoses.

The Justice Community Opioid Innovation Network (JCOIN) is another HEAL landmark project. It involves a network of researchers that is working with judges and with the workers in jail and prison systems responsible for taking care of individuals with substance use disorders. Through this network, we’ve been able to start to harmonize practices. One thing that’s been transformative in the jail and prison system has been the embracing of telehealth. In the past, telehealth was not much of a reality in jails and prisons because of the fear of it could lead to communications that could perhaps be considered dangerous. That’s changed due to COVID-19. Now, telehealth is providing access to treatment for individuals in jail and prison, many of them with substance use disorders.

Also, because of COVID, many nonviolent individuals in jails and prisons were released. This gives us an opportunity to evaluate how best to help such individuals achieve recovery from substance use disorders. Hopefully we can generate data to show that there are much more effective strategies than incarceration for dealing with substance use disorders.

The HEALing Communities Study, involves Massachusetts, New York, Ohio, and Kentucky—four of the states with the highest rates of mortality from overdoses from the inception of the opioid epidemic. By implementing a battery of interventions for which there is evidence of benefit, this ambitious study set out to decrease overdose mortality by 40 percent in two years. Then, came COVID and turned everything upside down. Still, because we consolidated interactions between agencies, we’ve been able to apply support systems more efficiently in those communities in ways that have been very, very reinforcing. Obviously, there’ve been delays in implementation of interventions that require in-person interactions or that involve hospital emergency departments, which have been saturated with COVID patients.

We’ve learned a lot in the process. I may be too optimistic, but I do believe that we can stay on goal.

Collins: Now, I’d like to transition to a few questions from people who subscribe to the HEAL website. Announced at this meeting three years ago, the HEAL Initiative involves research participants and patients and stakeholders—especially people who have lived experience with pain, addiction, or both.

Let’s get to the first question: “What is NIH doing through HEAL to address the stigma that prevents people who need opioid medications for treatment from getting them?”

Volkow: A crucial question. As we look at the issue of stigma, we need to recognize that there are structural issues in how our society is prioritizing the importance of substance use disorders and the investments devoted to them. And we need to recognize that substance use disorder doesn’t exist in isolation; it is frequently comorbid with mental illness.

We need to listen. Some of the issues that we believe are most problematic are not. We need to empower these communities to speak up and help them do so. This is probably one of the most important things that we can do in terms of addressing stigma for addiction.

Collins: Absolutely. The HEAL Initiative has a number of projects that are focusing on stigma and coming up with tools to help reduce this. And here’s our second question: “In small communities, how can we provide more access to medications for opioid use disorder?”

Volkow: One project funded through HEAL was to evaluate the effectiveness of community pharmacies for delivering buprenorphine to individuals with opioid use disorder. The results show that patients receiving buprenorphine through community pharmacies in rural areas had as good outcomes as patients being treated by specialized clinicians on site.
Another change that’s made things easier is that in March 2020, the DEA relaxed its rules on how a physician can prescribe buprenorphine. In the past, you needed to go physically to see a doctor. Now, the DEA allows a patient to be initiated on buprenorphine through telehealth, and that’s opened the possibility of greater access to treatment in rural communities.

My perspective is let’s look at innovative ways of solving problems. Because the technology is changing in so many ways and so rapidly, let’s take advantage of it.

Collins: Totally with you on that. If there’s a silver lining to COVID-19, it’s that we’ve been forced to take stock of the ways we’ve been doing things. We will learn from this pandemic and change the way we approach so many things in health and medicine as a result. Certainly, opioid use disorder ought to be very high on that list. Let’s move on to another question: “What is the HEAL initiative doing to promote prevention of opioid use?”

Volkow: This is where the HEAL initiative is aiming to provide alternative treatments for the management of pain that reduce the risk of addiction.

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Then there’s the issue of prevention in people who start to take opioids because they either want to get high or escape. With the COVID pandemic, we’ve seen increases in anxiety and in depression. Those are factors that can put a teenager or young adult on a trajectory for higher risk of substance use disorders.

So, what is HEAL doing? There is prevention research specifically targeted, for example, at the transition from adolescence to young adulthood. That is the period of greatest vulnerability of uptake of opioids, or drugs of misuse. We’re also targeting minority groups that may be at very, very high risk. We want to be able to understand the factors that make them more vulnerable to tailor prevention interventions more effectively.

Collins: Today, we’ve shared some of the issues that NIH is wrestling with in its efforts to address the crisis of opioid misuse and overdose, as well as other drugs that are now very much part of the challenge. To learn more, go to the HEAL website. You can also send us your thoughts through the HEAL Idea Exchange.

These developments give me hope in the wake of a very difficult year. Clearly, we still have the capacity to work together, we are resilient, and we are determined to put an end to our nation’s opioid crisis.

Volkow: Francis, I want to thank you for your incredible leadership and your support. I hope the COVID pandemic will bring forth a more equitable system, in which all people are given the chance for resilience that maximizes their life, happiness, and productivity. I think science is an extraordinary tool to help us do that.

Links:

Video: The 2021 Rx Drug Abuse & Heroin Summit: Francis Collins with Nora Volkow (NIH)

COVID-19 Research (NIH)

Helping to End Addiction Long-term (HEAL) Initiative (NIH)

HEAL Idea Exchange (NIH)

National Institute on Drug Abuse (NIH)

Rx Drug Abuse & Heroin Summit, A 2021 Virtual Experience


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