With Gratitude to the Hewit Family Foundation —
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Ms. Johnston and Mr. Andrews, On behalf of the CU Anschutz Medical Campus, thank you for the Hewit Family Foundation’s investments in a shared vision for improving the lives of people with Alzheimer’s disease and related dementias, as well as those with substance abuse disorders and liver diseases. Your incredible generosity continues to open up countless possibilities in the development of new treatments and therapies, and we are honored by your partnership. In this report, we have highlighted some of the ways that your support has kept us at the forefront of innovation and discovery. Your investments have positioned us well to take our research to new heights, and to advance our ability to transform the lives of more patients and their families. Thank you for the work you make possible with your support.
Donald M. Elliman, Jr. Chancellor, University of Colorado Anschutz Medical Campus
Your Support of Alzheimer’s Disease Research Since Huntington Potter, PhD, arrived at the CU Anschutz Medical Campus eight years ago, the University of Colorado Alzheimer’s and Cognition Center (CUACC) has made important progress in the treatment of Alzheimer’s disease and related dementias. The CUACC’s clinical and research expertise has grown from a single neurologist with around 100 clinic visits each year to a staff of 50 physicians and researchers with over 3,000 clinic visits each year. Support from benefactors like you allows us to achieve our goal of engaging in innovative research with the potential to change lives, while also providing exceptional clinical care today. Thanks to our partnerships, the CUACC is now one of the major Alzheimer’s research centers in the country. With your help, we are advancing Leukine® as a potential effective treatment to be offered in the clinic, and we are narrowing down our research into other molecules that could alter the trajectory of Alzheimer’s disease. Thanks to benefactors like you, we now have five new promising drug candidates to move into organoid and then animal model studies, with the goal of launching the best in a human clinical trial. We are also exploring the role of sleep in Alzheimer’s and how we may change the course of Alzheimer’s through sleep interventions, and we are developing a better understanding of the role of the immune system in Alzheimer’s and healthy aging.
HEPATOLOGY
SUBSTANCE ABUSE
ALZHEIMER’S
HEWIT FAMILY FOUNDATION GIVING
$1,000,000 pledge
1988
2005
The Hewit Family Foundation begins over three decades of support for various efforts at CU Anschutz including cancer research, AIDS education, scholarships, preventative medicine, OB/GYN and dental medicine.
MILESTONES
• Dr. Hugo Rosen is recruited to the CU Anschutz Medical Campus, citing the Hewit family’s transformative gift as a key reason for relocating to Colorado
2007 • Dr. Greg Everson founded HepQuant, LLC in order to commercialize his invention of novel technology for noninvasive assessment of chronic liver disease
2009 • National Institute on Drug Abuse (NIDA) renewed P60 center grant, which brought $10,733,993 to CU between 2009 and 2015 for drug abuse research
All scientific research, especially in the complex field of neurodegeneration and Alzheimer’s, requires collaboration at every stage – between scientists, with participants in clinical trials and observational studies, and with philanthropists who support the early steps toward the discovery of new diagnostics and treatments. We and our current and future patients are grateful for the Hewit Family Foundation’s ongoing support. HUNTINGTON POTTER, PhD Director, CU Alzheimer’s and Cognition Center Kurt N. and Edith von Kaulla Memorial Professor of Neurology Vice Chair of Basic Research, Department of Neurology
Promising Results from the Pilot Leukine® Safety Trial
40
In our recently completed Pilot Leukine® Safety Trial, our primary aim was determining the safety of Leukine® in humans with mild-to-moderate Alzheimer’s disease. We also had secondary aims of determining the efficacy of Leukine® in improving cognition and removing amyloid from the brain.
total research participants with mild-to-moderate Alzheimer’s disease
This trial included 40 total participants, with half receiving Leukine® and half receiving placebo injections five days per week for three weeks. The participants were analyzed throughout the treatment phase, and then at intervals of 45 days and 90 days post-treatment. With the support of private foundations, we were able to include amyloidPET imaging for the final 20 out of 40 research participants. The goals of including this imaging were to assess whether amyloid load reduction was noticeable in participants that received Leukine®, and to further validate that the participants indeed had Alzheimer’s disease. These efforts were critical as some scientists believe other drug trials have often failed because the participants did not all have Alzheimer’s.
20
received a placebo
HEPATOLOGY
20
received Leukine®
SUBSTANCE ABUSE
0
Results of the trial have been submitted for scientific peer review and publication. Given the optimistic findings of this trial, we were selected to give an oral presentation at the Clinical Trials on Alzheimer’s Disease (CTAD) Conference this November.
ALZHEIMER’S
•
2010
• $3.9 million NIH grant awarded to Dr. Rosen’s liver disease research
serious adverse events from Leukine®
The final trial results indicated that Leukine® is safe in humans with mild-tomoderate Alzheimer’s, as individuals who received Leukine® experienced no drug-related serious adverse effects. Our final analysis of the data also showed that those who received Leukine® demonstrated improved cognition on the Mini-Mental State Exam. We ultimately were not able to prove causation of amyloid reduction in the brains of participants that received Leukine®, but the amyloid-PET imaging did indicate a correlation with cognitive changes in the combined Leukine® and placebo groups, which is suggestive. It is likely the number of participants with amyloid-PET imaging who received Leukine® was too small of a data set to see statistically significant amyloid reduction results, and that the drug treatment period was too short. We will again assess whether amyloid load is reduced for individuals receiving Leukine® in the next phase trial.
2011
• Dr. Rosen published “Chronic Hepatitis C Infection” in the New England Journal of Medicine
• World Health Organization and President Obama declared July 28 to be recognized as World Hepatitis Day
2012
• Drs. Crowley and Sakai made progress in showing that when adolescents with conduct disorders and substance dependence make risky decisions, their brains function differently; data has led to investigating underlying mechanisms that may eventually lead to a cure
Launching the Leukine® Safety/Efficacy Trial
In this longer and larger trial, 42 individuals with mild-to-moderate Alzheimer’s will receive injections of Leukine® (28 participants) or placebo (14 participants), five days a week for 24 weeks. Key takeaways from the completion of the Pilot Leukine® Safety Trial led us to recently redesign elements of the longer Leukine® Safety/Efficacy Trial, including having participants or their caregivers administer the injections, and including cerebral spinal fluid (CSF) to track different biomarkers. The participants will continue to be assessed after 24 weeks of treatment, at intervals over six months.
Improvement in Mini-Mental State Exam score 3
We are currently in the process of gaining all approvals from the University of Colorado and the state for this trial. The date of recruitment for the first subjects will depend on the speed of those approvals and how quickly clinical trials resume due to the COVID-19 pandemic. The support we have received from another private foundation will be deployed immediately to support this trial, along with funds from the Alzheimer’s Association’s global research grant program, Part the Cloud. These investments provide a runway to launch this trial, while we continue to close the $3.9 million gap in cost through National Institutes of Health (NIH) grant applications and other private foundations and philanthropic support. We anticipate that we will take approximately four years to complete the trial and analyze the results. This work could be accelerated should we acquire additional funding for hiring more staff.
$122,070 gift $122,070 gift
• Dr. Huntington Potter joined CU Anschutz to begin building a comprehensive Alzheimer’s Center
• NIDA granted CU $1,368,209 between 2012 and 2017 for imaging research related to adolescent drug use
2013
• Dr. Rosen published “Emerging Concepts in Immunity to Hepatitis C Virus Infection,” one of more than 100 papers on the topic of hepatitis C immunology
2014
EOT
2 Delta MMSE Total Score
The promising results from the Pilot Leukine® Safety Trial provide a strong foundation for moving closer to a true understanding of the promise of Leukine® to successfully treat Alzheimer’s disease. In the Leukine® Safety/Efficacy Trial, we will continue to monitor safety and long-term tolerability of the drug in individuals with mild-to-moderate Alzheimer’s disease. We will also be testing the hypothesis that Leukine® improves cognition, removes amyloid from the brain and improves other biomarkers of Alzheimer’s disease, indicating the drug’s effect on altering the disease process.
• Pilot Leukine® Safety Trial for mild-moderate Alzheimer’s enrolled first subject at CU Anschutz
FFU
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Placebo GM-CSF
-3 0
20
40 60 Time (Days)
80
100
Cognitive Improvement measured in Pilot Leukine® Safety Trial The graph shows that Leukine® treatment (black line) improves memory compared to placebo (gold line) in participants through the end of treatment (EOT) and that the benefit continues for 45 days after the EOT until the first follow-up visit (FFU).
Exploring Potential Alzheimer’s Disease Biomarkers Several avenues of biomarker research are advancing at the CUACC. For example, Brianne Bettcher, PhD, studies the biological mechanisms that contribute to how people age, with a special focus on the role of the immune system in memory decline. In order to examine how the immune system might contribute to brain aging, Dr. Bettcher’s program focuses on the identification of biological indicators of a disease, called “biomarkers,” and how they relate to cognitive functioning. Biomarkers include immune markers and Alzheimer’s disease-related proteins that are carried in the blood and in the cerebrospinal fluid (CSF) that surrounds the brain and spinal cord. Dr. Bettcher is especially interested in studying CSF because it provides unique insights into specific proteins that may contribute to brain health that cannot be captured in bloodwork or brain scans.
With your generous support, we are better able to recruit, comprehensively assess, and track aging adults in the community over time, which is critical to our understanding of Alzheimer’s and other devastating brain diseases. Your support has allowed us to continue momentum in our aging and biomarkers studies that we believe will ultimately help us improve early diagnosis and treatment of neurodegenerative diseases in aging adults. We are committed to the highest caliber of studies, and, with your help, are truly optimistic about the future of treatment and possible prevention of Alzheimer’s disease. BRIANNE BETTCHER, PhD Associate Professor, Department of Neurology
Christina Coughlan, PhD, collaborates with Dr. Bettcher at the CUACC on her studies through the exploration of small vesicles, called exosomes, found in large quantities in blood. These vesicles carry material that is thought to play roles not only in normal healthy individuals, but also in the spread of disease, such as Alzheimer’s disease and related dementias. Nearly all of the body’s cells, including brain cells, secrete exosomes continuously into the blood, and if they carry toxic proteins, the exosomes may inadvertently deliver them to other cells. In collaboration with others, Dr. Coughlan is investigating biological blockers that could prevent this transmission and halt disease progression. They are also exploring how exosomes might be used to help clear toxic proteins in Alzheimer’s disease, or even to help deliver targeted drug therapies into cells.
HEPATOLOGY
SUBSTANCE ABUSE
ALZHEIMER’S
$2,500,000 pledge
• NIDA Adolescent Brain & Cognitive Development study began; consortium of University of Minnesota, Washington University, Virginia Commonwealth University and University of Colorado
$200,000 gift
$100,000 gift
2015
2016
• Small molecule drug library screens for potential new Alzheimer’s drugs began
• Published findings that adolescents with addiction have brain differences during risky or cautious decision-making
• Published papers examining prosocial and antisocial behaviors, and their relation to addiction
Your Support for Substance Use Research Thank you for your support of our lab’s goal of better understanding the neurobiological underpinnings of early onset substance use disorders and related conditions, with the hope that we can one day have more powerful treatments for patients. With the tremendous support of the Hewit Family Foundation, we have made important progress in moving promising research forward to help develop tailored interventions that may more effectively treat individuals with substance use disorders. We hope that you share in our pride for the accomplishments made possible with your support.
An Update from Dr. Sakai’s Lab In recent years, we have focused on two main areas, including enhancing our understanding of the social neuroscience of addiction and moving toward developing a first-of-its-kind trial of deep brain stimulation (DBS) for the treatment of cocaine use disorder. Our efforts in the development of behavioral paradigms and brain imaging approaches to better understand the links between social neuroscience and drug use have led to multiple publications. Our preliminary work supported by the Hewit Family Foundation has now developed to the point where we were able to submit a R01 grant to National Institute on Drug Abuse (NIDA), where it is currently under consideration for funding.
Our cutting edge work on DBS for cocaine dependence is of interest to NIDA for funding. In September we received a “Just-In-Time” request from NIDA. This is done when the agency is strongly considering a grant for funding. We are successfully navigating the protocol requirements that are required for funding. NIDA’s interest is a good sign but we will need to provide further data. Your continued support in this area is critical to continuing this important work in addiction.
$125,000 gift
• Began developing Leukine® mimetics • Began studies to develop a ‘blood test’ for Alzheimer’s by assessing exosomes
2017
• NIDA Adolescent Brain & Cognitive Development consortium received $4,720,631 in funding • Published research indicated that 9-11-year-olds at high risk for developing addiction had impaired reward circuitry and frontal regions in the brain when deciding to behave in a risky manner
• Positive interim Pilot Leukine® Trial results showing improved cognition reported at Alzheimer’s Association International Conference (AAIC) • Department of Defense awards $357,473 grant to study the relationships between traumatic brain injury and Alzheimer’s
• Started developing ‘mini brains’ to test potential new Alzheimer’s drugs
We are very grateful for the support of the Hewit Family Foundation, as it has provided us with the opportunity to do truly novel work in the field of substance use disorders. We are excited about the possibilities of utilizing brain stimulation techniques, including transcranial magnetic stimulation, to improve addiction treatment outcomes. And, we are looking forward to advances in the next decade that could bring care to people suffering from addiction. JOSEPH SAKAI, MD Associate Professor, Director, Medical Student Education Department of Psychiatry, CU School of Medicine
A Message from the Department Chair Ms. Johnston and Mr. Andrews, I am pleased to inform you that the CU Department of Psychiatry’s Division of Addiction Science, Prevention and Treatment is one of the department’s strongest and most active divisions with respect to clinical care, education and research. Each year, our robust addiction and co-occurring treatment programs attract psychiatry residents and fellows from across the country for continued education and training. Many remain affiliated with the department or practice in other areas of Colorado, spreading expertise in addiction psychiatry throughout the region. As the chair of the department, I’m fully committed to the enhancement and growth of our addiction and co-occurring programs to support the mental health needs of Coloradans suffering from alcohol and drug abuse, and the psychiatric disorders that frequently co-occur with addiction. Our clinical programs span a large swath of the state through telemental health, state contracts and federal research dollars.
C. NEILL EPPERSON, MD Professor and Chair, Department of Psychiatry Robert Freedman Endowed Professor of Psychiatry CU School of Medicine
Support from the Hewit Family Foundation has been critical to the growth of research in addiction sciences, promoting new knowledge regarding novel treatments for addictions, including opioid use disorders. The use of deep brain stimulation will be greatly advanced both here in Colorado and nationally through Dr. Sakai’s careful and ground-breaking research. Thank you for your support for novel therapies, which will bring hope to many individuals suffering from the devastation of addiction. Sincerely,
C. Neill Epperson, MD
HEPATOLOGY
SUBSTANCE ABUSE
ALZHEIMER’S
$400,000 pledge
• Dr. Everson, professor of medicine, retired from the School of Medicine after making pioneering contributions to the treatment and care of people with hepatitis C, a condition that was not even known when he was beginning his career
2018
• Positive interim Pilot Leukine® Trial results showing improved cognition and reduced amyloid reported at AAIC
• Alzheimer’s Association awards $1 million Part the Cloud grant for longer and larger, Leukine® Safety/Efficacy Trial
• Memory Disorders Clinic patient visits reach over 3,000 per year — an increase from around 100 in 2012 thanks to growth of clinical team to include six neurologists, one neuropsychologist, three nurse practitioners, and one fellow
• Dr. Rosen is recruited to serve as chair of the Department of Medicine at the Keck School of Medicine, University of Southern California
• During his tenure at CU, Dr. Rosen recruited 45 faculty members, established new multidisciplinary programs, garnered more than $11M in federal research support, including two Hep-C Research Centers and four VA Merit review grants and transformed the division into one of the highestrated divisions in the country
Your Support for Hepatology Research In the years that Hugo Rosen, MD, was part of CU Anschutz, he transformed the Division of Gastroenterology and Hepatology into one of the highest-rated divisions in the country. With the support of the Hewit Family Foundation, Dr. Rosen’s research career was significantly bolstered. During the period of support, Dr. Rosen published more than 80 papers on the topic of hepatitis C immunology and garnered more than $3 million in research support. His work has made major inroads to our understanding of chronic persistence of hepatitis C in human patients and has, in part, contributed to the development of drugs to treat hepatitis C. Your early support for Dr. Rosen’s work has helped the next generation of researchers continue our momentum to inform treatments and therapies that will ultimately help us improve lives. One of our emerging leaders in liver disease is Beth Tamburini, PhD.
2019
• Protocols and approvals finalized for Deep Brain Stimulation (DBS) Trial for cocaine addiction • CU Anschutz conducts its first transplant of a liver infected with hepatitis C to save a patient’s life, then cures patient of hepatitis C
• Final subject completed Pilot Leukine® Trial • Bio-AD study has enrolled 142 participants to search for biomarkers of Alzheimer’s
• Awarded NIH grant of $3,236,543 for the study, “Investigating the Contribution of Peripheral versus Central Nervous System Immune Dysfunction to Cognitive Aging”
• Awarded $777,499 Department of Defense grant for the study, “Investigating Immune Biology and Alzheimer’s Disease-Related Biomarkers in Asymptomatic, Late Life Mild Traumatic Brain Injury”
The Hewit Family Foundation’s support was transformative, and a key reason why I came to Colorado, where I headed the Division of Gastroenterology and Hepatology for more than a decade. During that time, the research and clinical portfolio of the division more than doubled, and I recruited almost 50 faculty. It was exciting to be on the front line of the evolution of hepatitis C treatment at CU Anschutz. During this time, we definitely had one of the best liver groups in the country. I am very grateful for your kind support of hepatitis C research and I enjoyed interacting with such a wonderful family as yours. HUGO ROSEN, MD Professor and Chair, Department of Medicine Keck School of Medicine of USC
Beth Tamburini, PhD
Philanthropy makes high-risk and high-reward projects possible, allowing us to address new questions as we work at the cutting-edge of research to develop potential therapeutic targets. Without private support, our success in developing novel treatment options for chronic liver disease would be limited. BETH TAMBURINI, PhD Assistant Professor of Medicine, Division of Gastroenterology and Hepatology
Our research goals are aimed toward developing treatments for chronic liver diseases by evaluating new potential therapeutic targets. One of our major interests is understanding how the lymphatic system regulates organ homeostasis. The lymphatic system is a circulatory system that maintains fluid homeostasis and assists in the transport of immune cells to the lymph node for immune surveillance. In an attempt to maintain liver function, the lymphatic vessels within the liver expand dramatically during disease to accommodate excess fluid and immune cell infiltrate. However, inflammatory factors, such as a cholesterol, accumulate in the liver during chronic liver disease and impede lymphatic function. Loss of lymphatic function within the liver compounds liver inflammation and worsens disease. Our future studies are aimed at understanding how these inflammatory factors affect lymphatic function within the liver in order to develop therapeutics to improve lymphatic function and overall liver health.
HEPATOLOGY
2020
SUBSTANCE ABUSE
Invited to present Pilot Leukine® Safety Trial results to Clinical Trials on Alzheimer’s Disease Conference
ALZHEIMER’S
Thanks to research of leaders around the world, including Drs. Rosen and Everson, more than 98% of patients diagnosed with hepatitis C today can be cured. At CU Anschutz today, we are able to transplant livers from those infected with hepatitis C to healthy patients, and then cure the hepatitis C within 12 weeks
MORE THAN
98%
patients diagnosed with hepatitis C today can be cured
Ms. Johnston and Mr. Andrews, Thank you for your generous philanthropic investments at the CU Anschutz Medical Campus. Your partnership helps keep our skilled physician-scientists and researchers at the leading edge of innovation, and bolsters our mission of developing improved knowledge and delivering high-quality patient care. With your support, we continue to deepen our understanding of Alzheimer’s disease and related dementias, as well as substance use disorders and liver diseases. You also strengthen our ability to improve the quality of care for those who have these diseases. I offer our gratitude on behalf of our dedicated faculty and those whose lives depend on our work. We sincerely appreciate your contributions to this vital work. We look forward to our continued partnership and all that we will accomplish together.
Thank you,
John J. Reilly, Jr., MD Dean, CU School of Medicine Vice Chancellor for Health Affairs Richard D. Krugman Endowed Chair