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Story of a CU Anschutz-driven breakthrough

Nichol Miller and family

Under the sunny skies that return to Portland, Ore., every summer, Nichol Miller is enjoying a life of family and purpose. The mother of three soaks in the milestones of graduations, weddings and anniversaries as well as the simple pleasures of seeing her kids head off to school and her husband come home from work.

All this seemed improbable just a few years ago – even impossible. Stricken with an aggressive soft-tissue sarcoma that started in her hip flexor and quickly spread to her lungs, Miller traveled to Denver to participate in a clinical trial of an experimental therapy.

She called it her “hail Mary.”

Breakthrough in the making

At the CU Cancer Center at the CU Anschutz Medical Campus Miller met Robert Doebele, MD, PhD, associate professor of medicine, CU School of Medicine, who had found – thanks to an immortal cell line donated by another cancer patient – the abnormal gene NTRK1 in the cancer of that patient, who also happened to be a mother of three children.

Doebele’s discovery set the stage for a breakthrough therapy.

Nichol Miller and Robert Doebele
Nichol with Dr. Robert Doebele at the CU Cancer Center after undergoing the successful clinical trial drug for her aggressive cancer in 2015.

“The finding of an NTRK1 gene fusion in the lung cancer patient made me want to develop a therapy for patients with this type of genetic mutation as none had existed beforehand,” he said. “This led my lab to perform a number of experiments demonstrating that this gene was cancer-causing and, importantly, that cancer cells with this gene could be inhibited with a selective TRK inhibitor called ARRY-470, now better known as larotrectinib.”

When Miller arrived at the CU Cancer Center, breathing was almost impossible without five litres of oxygen per minute. Put on the targeted-therapy drug in spring 2015, called LOXO-101 at the time and taken orally as a pill, Miller showed immediate improvement.

FDA approves targeted-therapy drug

Miller still takes the drug, now commercially known as Vitrakvi, on cycles that start every 28 days. During the cycles ­– she’s currently on her 56th – Miller takes the pill twice a day, and will continue doing so for the rest of her life.

She and her family celebrated when the Food and Drug Administration (FDA) approved Vitrakvi last November.

Early on in the development of targeted therapies, Doebele said, researchers saw examples of cancers such as EGFR mutation-positive lung cancer in which mutations seemed to occur in only one type of cancer, or that perhaps a therapy would only work on a mutation when it was found in certain types of cancer.

“When we started planning the clinical trial (of LOXO-101) I had the idea, based on data from our laboratory showing that lung, colon and leukemia cells responded to therapy as long as they had the right genetic fusion in an NTRK gene, that we should include any tumor type as long as it had an NTRK gene fusion,” Doebele said.

Drug attacks the genetic markers in cancer

Because Miller’s tumors had this specific gene fusion, the therapy had the desired effect: her lung tumors began to shrink and disappear and tumor markers in her blood showed dramatic declines. The drug works by targeting the proteins that are abnormally turned on by a gene fusion event. It essentially kills the cancer or stops it from growing.

“The term is ‘tumor agnostic,’ and that’s part of what’s unique about this drug,” Miller said. “It’s not linked to a particular cancer, or where a cancer is found in the body, but linked instead to the genetic markers in the cancer.”

Now her life is marked by milestones.

‘Lab saved my life’

This spring, Miller, 46, got to see her oldest son get decked out for prom and then graduate from high school. For her birthday in March, she and her husband enjoyed a week in Florida – the first time in 18 years of marriage they vacationed without their children.

Nichol Miller is now a cancer patient advocate, frequently speaking in her home state of Oregon as well as during a recent trip to Denver. Here, she is pictured with fellow presenters at an Oregon Health & Science University panel. Pictured from left: Lara Davis, MD; Miller; Summer Gibbs, PhD; and Shannon McWeeney, PhD.

“I wouldn’t be talking to you without (the clinical trial at the Cancer Center),” she said. “It was huge. It was my miracle. It gets easier with time, but I still think about how close I came (to dying), and it makes you appreciate everything so much more and gives you a lot more patience.”

Miller likes to say “the lab saved my life” because she gives full credit to the important cancer studies being performed by researchers at the CU Cancer Center as well as, closer to her home, the Oregon Health & Science University. The gene mutation found in her cancer is very rare; only 1 to 3 percent of all solid cancers have the NTRK1 mutation.

“I wouldn’t be here without the all the work of the researchers and the doctors who are trying to solve the cancer puzzle.” – Nichol Miller

“I wouldn’t be here without the all the work of the researchers and the doctors who are trying to solve the cancer puzzle,” she said. “The genetic testing that found my alteration is incredibly important because the chances of finding something are rare, but for that one person it’s life or death. It’s a new way of looking at cancer.”

When physicians do genetic testing on a patient, Doebele said, they look not only for a specific mutation, such as NTRK, but rather a host of other rare genetic events that may already have, or may soon have, effective therapies.

A standout clinical trial

The clinical trial he administered to Miller stood out for a number of reasons. A key part was the 46-year-old mother who had never smoked but, by 2012, had developed metastatic lung cancer. Unfortunately, at the time there were no drugs available that could treat her illness. Before she died, the woman gave Doebele a sample of her tumor to grow an immortal cell line that could be used for further research and to test drugs against this type of cancer.

Nichol and Marc Miller
Nichol and her husband, Marc, take in the sunset at the Snake River gorge in Twin Falls, Idaho, on their return trip home from the clinical trial in Aurora in 2015. “We knew the drug was working,” Nichol says.

Her donation ended up helping another young mother, Miller, and potentially countless patients in the future.

“Her sacrifice and forethought is something I’m so grateful for,” Miller said of the patient who donated her cells. “I know that’s something people are working on at a national level – to make it easier for people to donate genetic material for research. There’s a lot of valuable information that just goes into the incinerator.”

And that’s another part of Miller’s clinical trial that stands out.

It shows how an understanding of cancer biology can reveal genetic markers which are tested in human tumors, thereby accelerating potential therapies to target the cancers, Doebele said. “We identified NTRK1 in lung cancer in 2012, published the initial laboratory findings in 2013 and 2014 and had started the trial by early 2014 with an FDA approval only a few years later in 2018.”

‘There’s always hope’

For Miller, telling her story and furthering the cause of genetic testing is now a big part of her purpose. She recently returned to Denver as a featured speaker at the “Stupid Cancer” conference, and she frequently shares her story at other venues as a patient advocate.

“My story is unique, and it’s a good story for giving people hope,” Miller said. “I read a lot of survivor stories and they’re what kept me going – knowing there’s always hope.”

Mainly, she’s joyful to share in the life of her family, and seeing her teenagers grow into healthy and happy adults.

“Ultimately, I’d like my children to grow up into a world where there is no longer a fear of cancer,” Miller said. “It doesn’t have to be a death sentence.”

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CU Anschutz researchers win grant to commercialize miniature microscope

A team of researchers from the University of Colorado Anschutz Medical Campus has received a grant to commercialize a miniature microscope that fits on the head of a mouse and can peer deeply inside the living brain.

The microscope, known as the 2P-FCM, uses an electrowetting lens mounted on the head of a freely moving mouse where a high-powered, fiber optic light can actually view and control neural activity as it happens. The lens is liquid and can change shape when electricity is applied.

Emily Gibson and Diego Restrepo examined the miniature microscope they developed with two professors from CU Boulder. The team won a $2 million NIH Brain Initiative grant to refine and expand the use of the instrument.
Emily Gibson and Diego Restrepo working on the miniature microscope that allows them to see inside a living brain.

“We can image deep into the brain which makes it very attractive to a lot of neuroscience researchers,” said Emily Gibson, PhD, assistant professor of bioengineering at CU Anschutz who helped create the microscope.  The initial demonstration of the 2P-FCM was published in Scientific Reports (Ozbay et al., 2018).

Gibson and her colleague Diego Restrepo, PhD, professor of cell and developmental biology at the University of Colorado School of Medicine, along with Karl Kilborn, co-president of 3i (Intelligent Imaging Innovations, Inc.) in Denver, won the $394,260 Small Business Innovation Research (SBIR) grant.

The microscope was first deployed to the University of Paris. Based on that success, it will next be used at New York University and Duke University.

The company 3i, founded by Karl Kilborn, along with Colin Monks, a former PhD student of CU Anschutz, and Abraham Kupfer, a former investigator at National Jewish, will produce the microscope. The company’s manufacturing efforts will be guided by Baris Ozbay, PhD, who helped create the prototype while working in Gibson’s lab and now works at 3i.

In 2016, Restrepo and Gibson along with Juliet Gopinath, PhD, associate professor in electrical, computer and energy engineering at CU Boulder and Victor Bright, PhD, professor of mechanical engineering at CU Boulder won a $2 million grant, spread over three years, from the National Institutes of Health (NIH) and the National Institute of Neurological Disorders and Stroke (NINDS). It was part of the NIH’s new BRAIN initiative aimed at revolutionizing the understanding of the human brain.

The money was partly used to optimize the microscope and deploy it in different neuroscience labs.

The device represents a breakthrough in the way scientists can observe brain activity. The microscope is attached to a thin fiber optic cable and mounted on a mouse’s head, allowing it to wander freely. Scientists can then observe complex neural processes within the brain.

“This can also be used to monitor brain responses to social and behavioral interactions,” Restrepo said. “To do that, you need an animal that is moving around and interacting with its environment.”

Kilborn, 3i co-president, said the goal of the BRAIN initiative was to ensure that new technologies developed academically made their way into as many laboratories as possible.

“This SBIR will help 3i disseminate the pioneering work done at CU Anschutz in the laboratories of Emily Gibson and Diego Restrepo, along with collaborators at CU Boulder in the laboratories of Victor Bright and Juliet Gopinath, which has also been funded, in part, by the BRAIN Initiative,” he said.  We are excited by the experimental potential of this new technology and believe the grant represents a positive example of how academia and industry can work together to advance research in neuroscience.”

The microscope will allow scientists to investigate a wide range of subjects.

Some of those involved with the project are studying the neural basis of vocal learning in songbirds, decision-making in non-human primates and the neural basis of social bonding among prairie voles.

“This microscope has been getting a lot of attention,” Gibson said. “The idea is to turn it into an easy-to-use commercial product and make it available to labs around the world. For me, that is what is most rewarding about this work.”

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Book focuses on ‘the how’ of implementing integrated healthcare

Integrated care handbook
The evidence-based handbook “Integrated Behavioral Health in Primary Care” is available through Springer Publishing and Amazon.

For decades, mental health was largely divorced from physical health. While this perspective has changed, primary care physicians continue the challenging task of revising their practices to encompass mental and behavioral healthcare.

They are turning to an emerging approach to primary care practice called integrated behavioral healthcare — an area in which the University of Colorado Anschutz Medical Campus is leading. This patient-centric model focuses on care that treats the whole person; it relies on the idea that the mind and body are not separable. In other words, patients’ primary care and behavioral healthcare providers work together to deliver the best care.

CU Anschutz’s very own, Larry Green, MD, and  Stephanie Gold, MD, co-edited a handbook to help guide this process, “Integrated Behavioral Health in Primary Care: Your Patients Are Waiting.”

Leadership for transforming care

This evidence-based handbook is intended to give practical, firsthand advice from real-world practices that can be applied by large and small, rural and urban, and public and private primary care practices around the world. It is broken down into chapters that focus on “the how” of what it takes to implement integrated care.

Larry Green, MD
Larry Green, MD, professor in the Department of Family Medicine

“This handbook can be used as a walkthrough for practice transformation,” said Gold, an assistant professor in the Department of Family Medicine in the University of Colorado School of Medicine. “It is a ‘how to guide’ on integrating behavioral health into primary care clinics. It provides much-needed guidance and support in how to approach to care delivery.”

Each chapter includes extra resources including articles and websites that can assist in implementation.

Collaborating to create change

Gold and Green, MD, a professor in the Department of Family Medicine, were contacted by Springer, publisher of the handbook, to edit the piece and organize other expert opinion.

“The book is grounded in lessons learned from pioneers in integrated care,” Gold said of her collaborators.

The intended audience stretches far beyond physicians; it is for anyone involved in primary care, including practice administrators and practice facilitators. The content is general enough to be applicable to practices across the world, save some policy information specific to the United States.

Stephanie Gold, MD
Stephanie Gold, MD, assistant professor in the Department of Family Medicine

“This can be used in any community,” said Green. “It’s a practical guide to help healthcare providers know what it takes to get this implementation work done.”

Progressing despite barriers

“There has been a persistent failure of providing proper healthcare for people with mental, emotional, and behavioral problems,” Green added. “Primary care practices everywhere cannot escape this. Patients are waiting for this kind of care. We just need to get on with it. We know how; let’s work together and do it.”

Integrated Behavioral Health in Primary Care is available now through Springer Publishing and Amazon.

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Grubstake Awards highlight remarkable return on investment

Grubstake awardees 2018-19

Pioneering research recognized by the 2018/19 Gates Grubstake Awards underscores promising strides in recent years in guiding basic science at the CU Anschutz Medical Campus toward commercialization and tangible benefits for patients.

Kenneth Liechty, MD
Kenneth Liechty, MD

The Grubstake Fund, with multiple awards of about $350,000 each year, is meant to bridge the “valley of death” funding gap that separates a promising medical concept from production and a business model that will make a difference in human lives.

It’s working.

The Gates Center for Regenerative Medicine and the CU Innovations Office, its Grubstake Fund collaborator, report that through early 2019, the cumulative $3.5 million in Grubstake awards had already produced nearly $20 million of follow-on funding from partners seeking to help develop and commercialize the concepts.

The more-than “5X” return is remarkable in any financial setting. For the Gates Center, it is confirmation that the mission of collaboration and entrepreneurship in the name of medical advancement is now producing results.

“The Grubstake Fund program has been so game-changing as far as impact and getting research to patients,” said Kim Muller, executive director of CU Innovations. “We are looking at using that model for all therapeutic areas around campus. We almost feel we have an ethical obligation to do it.”

This year’s winners

The 2018/19 Gates Grubstake Fund winners of $350,000 grants were selected from 15 applicants representing CU Anschutz schools, centers and institutes, CU Boulder, CU Denver and Children’s Hospital Colorado. They are:

  • Kenneth Liechty, MD, who is developing an inhaled formulation for the prevention and treatment of pulmonary fibrosis. Acute lung injury leading to Acute Respiratory Distress Syndrome (ARDS) causes 150,000 adult ICU admissions and 75,000 deaths annually in the US. Liechty and his team use nanoparticle therapy to regenerate healthy lung tissue in a mouse model of acute lung injury. The award will support an inhaled therapy and safety studies required prior to a clinical trial in ARDS patients.
  • Kunhua Song, PhD, for the regeneration of functional heart tissue from tissue damaged in a heart attack. Eight million Americans suffer a heart attack annually, and up to 40 percent of those develop heart failure. Despite the development of various therapies and medical devices, the five-year survival rate has not changed in the past 20 years. Song and his team have discovered a way to regenerate healthy cardiac cells from the fibrotic tissue causing heart failure using a gene therapy approach. The Grubstake Award will allow them to complete their animal studies and begin preparing to file an IND to enter clinical trials.
  • Michael Verneris, MD, for the generation of engraftable hematopoietic stem cells for use in bone marrow transplants. Bone marrow transplants are a high risk, high cost procedure used to treat leukemia, lymphoma, and genetic diseases. Autologous donation is the safest and quickest method. Recently, scientists have discovered how to create induced pluripotent stem cells (iPS cells) from a patient’s own cells, expand them, and convert them to bone marrow cells. So far these cells have not engrafted into the bone marrow of mouse models. Verneris and his team have discovered that adding a small molecule during the conversion of the iPS cells allows engraftment. The Grubstake Award will allow them to confirm their initial finding in animal models, and to determine the most promising small molecule for clinical and commercial use in humans.
Kunhua Song, PhD
Kunhua Song, PhD

To date, there are 105 ongoing regenerative medicine projects on campus with potential to compete for Grubstake awards, of which 25 have reached the product development stage. As word spreads of the program’s opportunities for researchers, being selected for the handful of awards has become increasingly competitive.

The Grubstake Fund goes a significant way toward addressing a gap between academia and “the real world” that has existed since the founding of medical schools. Researchers are constantly trying to broaden the impact of their work to help more than an individual patient. Yet when they have a promising concept, their scientific training lacks the background in regulatory approvals and how to access the capital required to prove a concept’s commercial value.

Intersecting with the private sector

“They’ve never had to intersect with the private sector,” Muller explained. “There’s no education in medical school or at work that helps them prepare for that.”

Members of the public who read casually about venture capital (VC) in hotbeds like California’s Silicon Valley may assume there are financiers with suitcases full of ready cash hovering around all PhDs. But that kind of capital tends to move in when an idea is ready for mass commercialization, innovation experts said. Before that stage, scientists need money for lab assistants and regulatory help to show that something seen under a microscope has real promise as a treatment.

“When you are at the proof-of-concept translational stage, that’s where most VCs aren’t going to invest,” said the Gates Center’s Entrepreneur in Residence Heather Callahan, who also serves as portfolio manager at CU Innovations, bringing the expertise of an Executive MBA, a law degree and a PhD in biochemistry. “That’s why this was the perfect place in the trajectory of invention to start putting money.”

The money and the mentoring have moved a growing portfolio of projects toward initial clinical trials in the next two to three years.

Michael Verneris, MD
Michael Verneris, MD

“The Gates Center has been phenomenally helpful in accelerating our work,” said Liechty, who received a previous Grubstake award in anti-inflammatory research. The Grubstake model and the Gates Biomanufacturing Facility address three keys to the drug commercialization process, he said: “It’s one thing to say, ‘Okay, we can manufacture things.’ Or another thing to say, ‘We have people who know the ins and outs.’ And another to say, ‘How do you pay for it?’ We’re a relatively new campus for that kind of idea, and this is what’s needed to really jumpstart this.”

Applications due at the end of August

The annual Grubstake award process has helped everyone involved with the Gates Center and wider campus research efforts keep an eye on the true significance of the scientific pursuit, said Gates Center Associate Director J. Mark Petrash, PhD.

“This is an important part of the mission of the university, to not only do good research but to make it of practical use to society,” he said.

Written applications for the 2020 round of Grubstake Awards are due at the end of August. Interested applicants are encouraged to reach out to the Gates Center’s Entrepreneur in Residence Heather Callahan for information.

Guest contributor: Michael Booth

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Scientists demonstrate the advantages of diverse populations when compiling genetic data

AURORA, Colo. (June 19, 2019) – Relying strictly on genetic data from those of European descent, rather than more diverse populations, can exacerbate existing disease and increase health care disparities, according to new research.

The research letter was published today in the journal Nature.

“There have been numerous discoveries in human genetics over the last few decades that have told us a lot about biology, but most of the work is being done on those of European descent,” said the study’s first author Christopher Gignoux, PhD, MS, associate professor at the Colorado Center for Personalized Medicine at the University of Colorado Anschutz Medical Campus. “By limiting our focus, we are limiting our understanding of the human genetics underlying complex traits. The PAGE Study gives us an overdue opportunity to look at what we can find when studying a large number of groups together.”

Associate Professor Chris Gignoux of the Colorado Center for Personalized Medicine.
Associate Professor Chris Gignoux of the Colorado Center for Personalized Medicine at CU Anschutz.

This was borne out in the study which examined thousands of individuals in the U.S. of non-European ancestry. The Population Architecture using Genomics and Epidemiology study (PAGE) was developed by the National Human Genome Research Institute and the National Institute on Minority Health and Health Disparities to conduct and empower genetic research in diverse populations.

Researchers genotyped 49,839 people and found a number of genetic variants replicated from studies strictly of European descent. But PAGE investigators found dozens of discoveries that would not have been possible in a single population study. This included both complex traits and in Mendelian, or monogenic disorders.

“In light of differential genetic architecture that is known to exist between populations, bias in representation can exacerbate existing disease and health care disparities,” the study said. “Critical variants can be missed if they have a low frequency or are completely absent in European populations…” Especially rare variants.


Kathleen Barnes, PhD, director of the Colorado Center for Personalized Medicine at CU Anschutz
Kathleen Barnes, PhD, director of the Colorado Center for Personalized Medicine at CU Anschutz

Gignoux said the success of precision medicine and genomics means recruiting people from underrepresented populations for genetic studies. Right now, those genomic databases lack critical diversity despite the fact that many of in underrepresented groups have the greatest health burden and stand to benefit the most from being included.

“The Colorado Center for Personalized Medicine on the Anschutz Medical Campus is committed to personalized medicine here in our state and region that will benefit ALL people, regardless of who you are or where you came from,” said Kathleen Barnes, PhD, director of the Colorado Center for Personalized Medicine. “Initiatives like PAGE, and the work summarized in this manuscript by Chris Gignoux and colleagues, show us the way forward in achieving our goals of inclusion. It also illuminates just how important genetic diversity is in our understanding of the architecture of genetic disease. These approaches can now feed into our personalized ancestry information resource for patients interested in their own ancestry, as well as benefit our research and clinical community.”

Gignoux agreed.

“With studies of diverse groups we got a better overall picture of the genetic architecture which show the underpinnings of disease,” Gignoux said. “We want to understand how genetics can improve and ameliorate disease rather than make it worse.”

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Tanning industry uses promos, cheap prices to lure adolescents and young adults

Woman laying in tanning bed

It’s well-known that cigarette smoking causes cancer and as a result, prices and advertising are closely regulated to discourage youth from starting.  But another cancer risk, indoor tanning, shown to cause melanoma, lags in regulation.

Researchers at the Colorado School of Public Health have found that the tanning industry uses marketing strategies that appeal to adolescents and young adults, including unlimited tanning packages, discounts, and even offering free tanning when paired with other services like an apartment rental or gym membership.

“This study highlights the fact that a lot of businesses out there are providing this service at a low cost which removes a barrier to adolescents and young adults,” said Nancy Asdigian, lead author of the study and a research associate in the Department of Community and Behavioral Health at the Colorado School of Public Health. “Young people who want to tan do so when they can afford it and don’t when they can’t.  The industry capitalizes on this with the strategies they use to price and promote this risk behavior.”

The study was published this week in the Journal of Public Health Policy.

According to the Global Burden of Disease Study, about 352,000 people worldwide were diagnosed with potentially deadly melanoma in 2015. That includes 81,000 cases in the U.S.

High profile public health and policy efforts along with state age restrictions have helped decrease the prevalence of indoor tanning among youth, but the study said levels remain  `unacceptably high.’

The researchers posed as customers and contacted tanning facilities in Akron, Ohio, Denver, Colorado, Austin, Texas, Boston, Massachusetts, Portland, Oregon and Pittsburgh, Pennsylvania. These cities were selected because they represent a variety of climate and geography as well as a range of stringency of state indoor tanning laws.

Of the 94 tanning places they contacted, 54 were primary tanning salons, and 40 were ‘secondary facilities’ that offered indoor tanning secondary to some other service like hair styling or physical fitness.

The study found that indoor tanning was free at 35 percent of secondary facilities. Nearly all apartments with tanning offered it free compared to 12 percent of gyms. Free tanning was most common in Austin.

Nearly all primary tanning salons offered time-limited price reductions.

“Many provide promos geared toward young adults. They offer packages that incentivize more frequent tanning. The more you use them the cheaper tanning becomes,” Asdigian said. “Everyone wants to get their money’s worth. When you buy a ski pass, you want to ski as much as possible.” In some cases, an individual tanning session could cost as little as $1 if the customer buys an unlimited monthly plan and uses it frequently.

Some countries, including Brazil and Australia, have banned indoor tanning salons altogether. The U.S. imposed a 10% tax on indoor tanning in 2010 and 19 states and the District of Columbia have enacted complete bans on indoor tanning for those under age 18.

But few of these policies have focused on the advertising, promotions or pricing practices of these facilities.

“A next step is to work with policymakers to restrict the use of discounts and deals to lure customers,” said Lori Crane, PhD, MPH, the study’s senior author and professor at the Colorado School of Public Health.

Another strategy would be to eliminate tanning provided in apartment complexes and fitness centers where tanning services are often free and less likely to be licensed and inspected by local regulators.

Asdigian said it’s important to understand the connection between pricing and the use of indoor tanning.

“In this study we described the costs and promotions,” she said. “An important question to answer is how variability in pricing impacts behavior. Establishing that link is an important step.”

The study co-authors include: Yang Lui; Joni A. Mayer; Gery P. Guy and L. Miriam Dickinson.




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Alzheimer’s FAQ

Alzheimer’s disease is the sixth leading cause of death in the United States, impacting millions of Americans and their families.

Here at the CU Anschutz Medical Campus, The Rocky Mountain Alzheimer’s Disease Center is focused on ending Alzheimer’s disease and other causes of dementia.

The Center’s Director, Dr. Huntington Potter, PhD, has answers to some common questions they receive on Alzheimer’s disease.

Dr. Huntington Potter Kurt N. and Edith von Kaulla Memorial Professor of Neurology; Vice Chair of Basic Research; Director, Rocky Mountain Alzheimer’s Disease Center

What causes Alzheimer’s disease?

Alzheimer’s is a complex disease caused by the accumulation of harmful proteins both inside and outside brain cells. These clumps, called plaques and tangles, kill healthy neurons and eventually lead to memory loss and other cognitive problems. What causes the beginnings of Alzheimer’s disease remains a mystery.

What are the first warning signs and early symptoms?

We want to stress, Alzheimer’s disease is not normal aging, but the very earliest symptoms are often misread as simply getting older: having less energy and drive, some forgetfulness or confusion, and mood changes. The name for the condition that precedes Alzheimer’s disease is called Mild Cognitive Impairment. Many people ignore the early signs when they should be seeing their doctors, asking for an evaluation.

How is someone diagnosed?

Historically, a diagnosis of Alzheimer’s was 100% accurate only after death and a brain autopsy. But more recently, physicians are able to make probable diagnoses while people are living, using brain imaging technology, multiple questions and answers, and an analysis of blood proteins.

Is Alzheimer’s hereditary?

Yes and no. Heredity often plays a role but it is not a guarantee. Many people with a family history of Alzheimer’s do not get the disease, and likewise, many with no family history can still develop Alzheimer’s. Alzheimer’s disease is the most common form of dementia, and the greatest risk for everyone is simply living longer.

What about prevention? Are there ways to keep the brain healthy as we age?

A healthy brain is often part of good overall physical health. Although there is no cure, there is research that says health-conscious living can delay the onset of dementing diseases, including Alzheimer’s. We sometimes say, “what’s good for the heart is good for the brain,” meaning a heart-healthy lifestyle is also a brain-healthy lifestyle. Getting lots of exercise, the right amount of sleep, a good diet, and staying engaged with people and creativity all make life more enjoyable with healthy brain benefits.

How can someone best help a loved one diagnosed with Alzheimer’s?

Continue to love and support the person and be mindful that the disease is no one’s fault. Beyond having a supportive attitude, families and individuals should get their affairs in order while they have the presence of mind to do so. Determine how care in both the short and long term can be provided. Don’t expect one person to have the capacity, know-how or interest to provide all the care. Build a network of care partners and get trained on how to properly manage the changes that are coming.

What are researchers at the Rocky Mountain Alzheimer’s Disease Center focused on? Are there any promising studies?

We have a large, dedicated team of scientists and clinicians at the University of Colorado Anschutz Medical Campus working together, studying how the disease develops and how it can be better diagnosed. We’re also developing new treatments in the laboratory that will be next tested in mice and, if successful, ultimately in humans.

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Cochrane US Network opens affiliate at CU Anschutz

The Cochrane US Network, made up of some of the country’s leading institutions in the research and practice of evidence-based medicine, announced Tuesday the opening of 11 new affiliates across the country including one at the University of Colorado Anschutz Medical Campus.

These new affiliates will join Cochrane’s 70 other groups around the world to promote evidence-informed decision making in health care by supporting and training systematic review authors and users of Cochrane Reviews, as well as working with clinicians, professional associations, policymakers, patients, health care provider organizations and the media to encourage the dissemination and use of Cochrane evidence.

Robert Dellavalle, MD, PhD, MSPH, professor of dermatology at the CU School of Medicine
Robert Dellavalle, MD, PhD, MSPH, professor of dermatology at the CU School of Medicine

“Cochrane is a leading evidence-based medicine organization, so it’s a very big deal to be a site that is tied to that effort,” said Robert Dellavalle, MD, PhD, MSPH, a professor of dermatology at the University of Colorado School of Medicine, who will lead the CU Anschutz affiliate. “Cochrane is known for having some of the best methodology for doing systematic review of evidence and they are highly cited in the field.”

The Cochrane US Network is made up of the existing Cochrane US West Associate Center based at Oregon Health & Science University; three Cochrane Review Groups producing systematic reviews in neonatal health, fertility regulation and urological conditions; three US satellites of Cochrane Review Groups focusing on eyes and vision, pregnancy and childbirth and musculoskeletal disease; one field specializing in complementary medicine. The 11 new affiliate institutions include:

  • AcademyHealth
  • American College of Physicians
  • Central Michigan University
  • Cornell University
  • Mayo Clinic Evidence-based Practice Center
  • Penn Medicine Center for Evidence-based Practice
  • RTI International – University of North Carolina Evidence-based Practice Center
  • Texas Christian University
  • University of Chicago Medicine
  • University of Colorado Anschutz Medical Campus
  • University of Maryland School of Medicine

Mark Wilson, Cochrane CEO, said: “I am delighted to see such a prestigious and committed group of US institutions and leaders in evidence-informed health care join Cochrane’s global family of collaborators.”

“Many of these researchers and clinicians are leaders in the field, and I am excited by the expertise, innovation and knowledge they will bring to our mission of delivering trusted evidence into health policy and clinical decision-making,” Wilson said. “The US health system is the largest and most sophisticated in the world, yet suffers from huge inequalities in health outcomes and tremendous wastefulness.”

Wilson believes a vibrant Cochrane Network promoting greater use of evidence showing what health interventions work and what don’t can make a real difference.

“I hope that this new – already extensive – network will grow further and welcome many more partners in the years to come,” he said.

These new Cochrane affiliates each have their own specific areas of expertise and focus. Collectively, the Network will focus on producing high quality evidence on priority topics for the US; providing training to systematic review authors and health care practitioners, policymakers and others in the interpretation of Cochrane Reviews. It will also raise the general awareness around Cochrane evidence to make well-informed health and health care decisions.  The new Network will build on the work of the former US Cochrane Center based at Johns Hopkins University.

“The establishment of the US Network is an important development for Cochrane as well as the health care community in the U.S.,” said Marguerite Koster, co-chair of the Cochrane Governing Board. “Coordination and collaboration are core values of the Network because we strongly believe we can add value by working together as a consortium. I very much look forward to the start of the network and to seeing it develop and grow as a platform for anyone interested in evidence-informed health and health care in the US.”

A formal launch of the new ‘Cochrane US Network’ was held today in Washington DC. During the launch meeting Cochrane CEO, Mark Wilson, and Governing Board co-chair, Marguerite Koster, introduced the US Network. Additionally, representatives from the Network will introduce their institutions and planned work, and speak to the value of being part of the Network.

The Cochrane US Network is part of Cochrane, a global independent network of researchers, professionals, patients, careers and people interested in health. Cochrane produces reviews which study all of the best available evidence generated through research and make it easier to inform decisions about health. Cochrane is a not-for profit organization with over 65,000 members and supporters from more than 130 countries working together to produce credible, accessible health information that is free from commercial sponsorship and other conflicts of interest. Cochrane’s work is recognized as representing an international gold standard for high quality, trusted information.


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Cannabis use among older adults rising rapidly

Cannabis Sativa leaf

Cannabis use among older adults is growing faster than any other age group but many report barriers to getting medical marijuana, a lack of communication with their doctors and a lingering stigma attached to the drug, according to researchers.

The study, the first to look at how older Americans use cannabis and the outcomes they experience, was published this month in the journal Drugs & Aging.

Hillary Lum, MD, PhD, assistant professor of medicine at the University of Colorado School of Medicine

“Older Americans are using cannabis for a lot of different reasons,” said study co-author Hillary Lum, MD, PhD, assistant professor of medicine at the University of Colorado School of Medicine. “Some use it to manage pain while others use it for depression or anxiety.”

The 2016 National Survey of Drug Use and Health showed a ten-fold increase in cannabis use among adults over age 65.

The researchers set out to understand how older people perceived cannabis, how they used it and the positive and negative outcomes associated with it.

They conducted 17 focus groups in in senior centers, health clinics and cannabis dispensaries in 13 Colorado counties that included more than 136 people over the age of 60. Some were cannabis users, others were not.

“We identified five major themes,” Lum said.

These included: A lack of research and education about cannabis; A lack of provider communication about cannabis; A lack of access to medical cannabis; A lack of outcome information about cannabis use; A reluctance to discuss cannabis use.

Researchers found a general reluctance among some to ask their doctors for a red card to obtain medical marijuana. Instead, they chose to pay more for recreational cannabis.

Lum said this could be driven by feeling self-conscious about asking a doctor for cannabis. That, she said, points to a failure of communication between health care providers and their patients.

“I think [doctors can] be a lot more open to learning about it and discussing it with their patients,” said one focus group respondent. “Because at this point I have told my primary care I was using it on my shoulder. And that was the end of the conversation. He didn’t want to know why, he didn’t want to know about effects, didn’t want to know about side effects, didn’t want to know anything.”

Some said their doctors were unable or unwilling to provide a certificate, the document needed to obtain medical marijuana. They also said physicians need to educate themselves on the latest cannabis research.

Some older users reported positive outcomes when using cannabis for pain as opposed to taking highly addictive prescription opioids. They often differentiated between using cannabis for medical reasons and using it recreationally.

“Although study participants discussed recreational cannabis more negatively than medical cannabis, they felt it was more comparable to drinking alcohol, often asserting a preference for recreational cannabis over the negative effects of alcohol,” the study said.

The researchers also found that despite the legalization of cannabis in Colorado and other states, some older people still felt a stigma attached to it.

“Some participants, for example, referred to the movie `Reefer Madness’ (1936) and other anti-marijuana propaganda adverts that negatively framed cannabis as immoral and illegal,” the researchers said.

The study adds to the growing literature on the diversity of marijuana use patterns in older adults, said co-author Sara Honn Qualls, PhD, ABPP, professor of psychology and director of the Gerontology Center at the University of Colorado Colorado Springs.

“Older adults who use marijuana are ingesting it in a variety of ways for multiple purposes,” she said.  “This and other papers from the same project show growing acceptance of marijuana use for medical purposes by older adults, and a clear desire to have their primary health providers involved in educating them about options and risks.

Lum agreed.

She said Colorado, the first state to legalize recreational marijuana, provides a unique laboratory to gauge public attitudes toward cannabis.

“From a physician’s standpoint this study shows the need to talk to patients in a non-judgmental way about cannabis,” she said. “Doctors should also educate themselves about the risks and benefits of cannabis and be able to communicate that effectively to patients.”

The study co-authors include: Julie Bobitt; Melissa Schuchman; Robert Wickersham; Kanika Arora; Gary Milavetz and Brian Kaskie.


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Symposium uses data to clear air-quality debate haze

On May 9, a conference room in the Education 1 building on the University of Colorado Anschutz Medical Campus steadily filled with smoke, ozone, particulate matter and a brew of other pollutants.

Well, not literally. The aforementioned air pollution agents were the focus of an Air Quality & Health Symposium hosted by the Colorado Air Quality Control Commission and the Colorado School of Public Health (ColoradoSPH). A series of speakers presented information about the most significant challenges to Colorado in maintaining safe air quality, including traffic increases, wildfires, accelerating growth and climate change, while the attending commissioners were updated on the latest evidence on air pollution and health.

Colorado is just one player in a global struggle to clean the air, noted ColoradoSPH Dean Dr. Jonathan Samet. After reviewing the scientific evidence and often contentious debate involved in setting air quality standards, Samet offered a blunt observation.

“There are billions around the world not breathing clean air,” he said.

Colorado’s efforts to reduce emissions

The symposium occurred in the aftermath of Colorado’s recently concluded legislative session, which saw passage of a number of bills aimed at reducing emissions that dirty the air. These include House Bill 1261, which establishes goals to reduce greenhouse gas emissions in the state at least 26 percent by 2025 and 90 percent by 2050. In addition, Governor Jared Polis in January issued an executive order supporting a “transition” to zero-emission vehicles in the state.

Jill Hunsaker Ryan
Jill Hunsaker Ryan, executive director of the Colorado Department of Health and Environment, said the transition to zero-emission vehicles in Colorado is “our highest priority.”

That transition is “our highest priority,” Jill Hunsaker Ryan, executive director of the Colorado Department of Health and Environment (CDPHE) told the crowd. “Transportation is the single greatest source of climate-changing emissions.”

Transportation is the only one of the big three sources of greenhouse gas emissions – power sources and the built environment round out the trio – that is expected to grow in the coming years, noted Taryn Finnessey, senior climate change specialist with the Colorado Department of Natural Resources.

Changing our sources of power

“We are changing our sources of power, but we are not necessarily changing the ways that we move as rapidly as we should be,” Finnessey said. She added that steps to “clean up our energy grid” by continuing to adopt renewable sources – there are now more than 57,000 clean energy jobs across the state – work hand-in-hand with electrifying transportation. Construction of charging stations for electric vehicles, begun in 2017, is well underway. Nearly three dozen stations, placed roughly every 50 miles along major highway corridors, are slated to be in place by 2020.

“Start car-shopping,” Finnessey quipped.

Rob McConnell, a professor at the University of Southern California (USC), pointed to the health risks posed by vehicle emissions, particularly to those who live nearby busy roadways. McConnell summarized the findings of USC’s 25-year Children’s Health Study, which followed some 12,000 children living in Southern California.

Researchers used spirometry tests to measure lung function in the participants and established a clear association between abnormally low lung function and living in communities with high particulate levels, McConnell said. The study also showed increased rates of childhood asthma among children who lived within 150 meters of a roadway.

Costs of poor air quality

The costs have been considerable: In Los Angeles County alone, some $400 million annually for asthma exacerbations attributable to pollution, and about half of that tied to near-roadway pollution, McConnell said. In the South Coast Air Basin, which encompasses much of greater Los Angeles, between 430 and 1,300 heart attacks were attributed to near-roadway pollution, generating costs of between $3.8 billion and $11.5 billion, he added.

‘There are billions around the world not breathing clean air.’ – Jonathan Samet, dean of the Colorado School of Public Health

Confronting these sobering statistics should be on the board for Colorado, McConnell said, noting the upcoming widening of I-70. He described steps taken in California to mitigate people’s exposure to pollution near roadways, including expanding mass transit, building high-density housing, and creating parks and other green spaces as buffers.

“By ignoring roadway pollution, we are missing an opportunity to improve air quality,” McConnell said.

Other speakers also noted the health risks posed by polluted air. Dr. Jennifer Peel, a professor of Epidemiology for ColoradoSPH and Colorado State University (CSU), cited data from the Health Effects Institute’s Global 2017 Burden of Disease assessment that pegged the worldwide number of premature deaths tied to fine particulate matter at 3 million. In the United States, the toll was 100,000 lives; in Colorado the number was 650, Peel said.

There is “solid evidence” tying short- and long-term exposure to particles of 2.5 microns (PM2.5) – about one-thirtieth the diameter of a human hair – to cardiovascular and respiratory disease and mortality, Peel said. But evidence is growing that these particles also have adverse effects on the central nervous system, including depression, cognitive decline and autism, she added.

The West Is hotter than ever

Peel cited wildfires as an important source of health-threatening particulate matter. As Finnessey and others noted, fires in Colorado and the West are more frequent and hotter than ever before.

Jonathan Samet at symposium
Dr. Jonathan Samet, dean of the Colorado School of Public Health (far left), fields a question from an audience member at the Air Quality & Health Symposium.

“The size and severity of wildfires has increased significantly over the past four decades,” Finnessey said. “And they are projected to continue to increase.” She noted that “science agrees” that without significant changes, the climate is expected to warm 2 to 6 degrees Fahrenheit by 2050. That rise will contribute to ever-thirstier and more heavily stressed ecosystems that are more vulnerable to prolonged drought and more intense wildfires.

And where there is fire there is smoke that can spread across states and regions. Dr. Colleen Reid, assistant professor in the Department of Geography at CU-Boulder, described her studies of the impacts of wildfires on air pollution and health. She said there is “clear evidence” associating wildfire smoke with respiratory health, including exacerbations of COPD and asthma. More studies of the long-term effects of exposure to wildfire smoke and possible public health interventions are needed, Reid added.

An important part of that effort is figuring out what exactly makes up that smoke. That’s the goal of Dr. Emily Fischer, assistant professor in the Department of Atmospheric Science at CSU. Fischer said wildfires often elevate PM2.5 levels on the ground, creating new emission-control challenges.

“Sporadic smoke events are offsetting improvements in mean PM2.5 air quality in some areas,” Fischer said.

‘Rivers of smoke’

Fischer led a National Science Foundation project called WE-CAN, which aimed to understand wildfire smoke by going to the source. She and fellow CSU scientists boarded a research airplane in 2018 that flew through “rivers of smoke” produced by western wildfires, with the aim of studying the composition of the thick plumes. Among the questions: how does the composition of smoke change as it ages and how does it contribute to rising levels of ozone, another primary air pollution issue.

The efforts to improve air quality also proceed on the ground. Dr. John Volckens, professor of Environmental and Occupational Health for ColoradoSPH and in CSU’s Department of Mechanical Engineering, described work with his team to develop an Ultrasonic Personal Aerosol Sampler (UPAS) that uses cell phone-assisted technology to measure individuals’ exposures to PM2.5. About 1,000 of the relatively inexpensive units are in operation around the globe, Volckens said.

Even more ambitiously, CSU partnered with NASA on a “citizen-science” initiative called CEAMS (Concerned and Engaged Community Members) that set up a network of air-monitoring stations around Fort Collins. The stations, manned by citizen volunteers, gather real-time air-quality data that supplement satellite imaging and the computer analysis that NASA uses to develop predictive air-pollution models.

The information from the monitoring network produced much useful information, Volckens said. For example, the team noticed elevated particle levels in the Old Town section of Fort Collins on cold winter nights. The reason: on those nights, the residents of the mostly old homes were lighting plenty of wood-burning fires.

“Science presents an opportunity to learn more about behavior and about how behavior and exposures [to air pollution] affect each other,” Volckens said. “I think we are only at the beginning of scratching the surface of that opportunity.”

Cleaner air on the horizon

But Volckens also cautioned that changing behavior is no easy task. And while Colorado now has plenty of initiatives on the table to address air-quality issues and climate change, the hard work of implementation is only beginning, Finnessey said.

“The challenge comes in figuring out what this all means and how do we achieve our goals,” she said.

Samet noted the “huge number of adverse” effects attributed to air pollution and the need for science to continue to generate as much evidence as possible about the risks dirty air poses. But in the end, he said, deciding on what to do with the data lies in policymakers’ unpredictable hands.

“The data still leaves those who make the decisions left to make those decisions,” Samet said.

This story was written by guest contributor Tyler Smith.

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