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Researchers say issues of dementia and gun ownership need more discussion

As the number of adults with Alzheimer’s disease and dementia steadily increases, questions around their access to firearms remain largely unaddressed, according to a study by researchers at the University of Colorado Anschutz Medical Campus.

“Firearm access, like driving, can pose a risk of injury or death to both cognitively- impaired individuals and those with whom they interact,” said the study’s lead author Marian (Emmy) Betz, MD, MPH, of the University of Colorado School of Medicine. “How can health care providers, family members and friends balance firearm-related safety concerns with the rights and wishes of the individual?”

The study was published Monday in the Annals of Internal Medicine.

Betz and her colleagues from institutions including Johns Hopkins University, the University of Michigan and the University of California Davis, examined clinical perspectives relating to assessment and counseling about firearm access for those with dementia or other cognitive impairment.

They found that nearly 4.7 million adults had Alzheimer’s in 2010 and that number was expected to grow to 13.8 million by 2050. The disease accounts for about 70 percent of all dementia cases. That means the total number of people with cognitive impairment and a firearm at home will also grow.

The study noted that even in the highly politicized atmosphere surrounding gun ownership, about 89 percent of Americans support limiting firearm purchases and access to those with a mental illness. Americans also support temporarily reducing gun access in times of elevated suicide risks.

Dr. Emmy Betz, associate professor of emergency medicine.
Marian Betz, MD, associate professor of emergency medicine

“The primary firearm injury risk for individuals with dementia is likely to be death by suicide,” said Betz, an associate professor of emergency medicine at the CU School of Medicine. “Some 91 percent of older adults’ firearm deaths are due to suicide, and firearms are the most common method of suicide among people with dementia.”

People with dementia can experience hallucinations, delusions, agitation or aggression. If a person is delusional and believes people are breaking into their home, they may feel caregivers and family members are intruders and confront them with a gun.

Betz said conversations about guns in these situations are similar to talks with older drivers.

“When is it time to give up the keys, be they to a gun safe or a car?” she asked. “What are the relevant state and national laws? When and how should conversations occur?”

Right now there are no validated screening tools for assessing firearm access among cognitively-impaired people. For those with milder forms of dementia, some experts recommend discussions with the patient and family about setting a `firearm retirement date.’

Caregivers can also ensure that guns are securely locked so the patient can’t have access without supervision. They can reduce risks of gun injury by making firearms less lethal – removing ammunition from the home, storing firearms unloaded or having trigger mechanisms removed.

Betz said physicians have a right and a duty to ask and counsel patients about potential health risks so long as they balance the welfare of the person with the health and safety of the public.

Federal law forbids the sale of a gun to someone judged `mentally defective’ or who has been committed to a mental institution. Still, federal and state laws don’t explicitly prohibit those with dementia from buying guns.

Betz said working with stakeholders in the dementia and firearms community would go a long way toward creating effective materials and programs to address this problem.

She and her colleagues have developed a sample family firearm document. The person with dementia would be able to sign the agreement before symptoms become too severe. The agreement says that when the person with dementia can no longer make the best safety decisions, the family can control the possession of his or her firearm.

“It’s best to have these conversations early and be aware that you have to take action at some point,” Betz said. “This is not about the government or anyone else seizing guns, but about a family making the best decision for everyone involved.”

The co-authors of the study include Alexander McCourt, JD, MPH, Johns Hopkins Bloomberg School of Public Health; Jon S. Vernick, JD, MPH, Johns Hopkins Bloomberg School of Public Health; Megan L. Ranney, MD, MPH, Rhode Island Hospital/Alpert Medical School; Donovan T. Maust, MD, MS, Department of Psychiatry, University of Michigan Center for Clinical Management Research, VA Ann Arbor Healthcare System; Garen J. Wintemute, MD, MPH, University of California, Davis School of Medicine.

 

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Donors celebrated for transformational gifts

More than 430 people attended the Benefactor Recognition Dinner, a celebration of the passionate people behind philanthropic gifts to the CU Anschutz Medical Campus. The event took place in the Seawall Ballroom in the Denver Performing Arts Complex on March 29.

This year’s gathering was particularly special because, for the first time, the recognition dinner included a celebration of CU Anschutz’s partnership with University of Colorado Hospital, and an acknowledgment of how philanthropic support makes an impact all across campus. Hosts of the evening included CU President Bruce Benson and his wife, CU First Lady Marcy Benson; CU Anschutz Chancellor Don Elliman; and University of Colorado Hospital President and CEO Will Cook.

Learn more about our generous honoree benefactors in the video presentations on this page.

“Our vision at CU Anschutz is simple,” Elliman said. “We seek to rise higher among the country’s top medical destinations; to be the place where anyone who needs it can get the finest care in the world; where the science of that care is being pushed to new horizons; and where we train and prepare the health workforce of our future.”

When Cook stepped to the podium, he said, “I hope you’re getting a sense of the momentum of our campus. The tremendous promise we’re seeing realized is what drew me to the University of Colorado Hospital from UPMC (University of Pittsburgh Medical Center) 2 ½ years ago.”

He added, “We’re pleased to be partnering more closely than ever with the university, as we work to rise even higher among the ranks of the country’s top destinations for health, wellness and world-class medical care.”

Elliman thanked the benefactors for their generous gifts, which help fuel the campus’s unprecedented growth. “You are a vital part of our growth and progress,” he said. “Because of you, we are in great shape and getting stronger.”

2018 honorees:

 

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Immune system dysfunction may occur early in Alzheimer’s disease

An association between inflammation biomarkers in both blood plasma and cerebrospinal fluid (CSF) and markers of Alzheimer’s disease (AD) associated pathology, has been found by researchers at the University of Colorado Anschutz Medical Campus working with the University of Wisconsin Alzheimer’s Disease Research Center and the University of California San Francisco Memory and Aging Center.

The discovery sheds new light on the pathology of AD as well as on the communication between the brain and the rest of the body. The findings were published today in the Journal of Alzheimer’s Disease.

Brianne Bettcher, PhD, assistant professor of neurosurgery and neurology at CU Anschutz
Brianne Bettcher, PhD, assistant professor of neurosurgery and neurology at CU Anschutz.

Scientists have long known that AD-related pathology may develop long before clinical symptoms of AD appear, and that inflammation is a core component of the disease. Previous studies have linked levels of inflammatory markers in CSF and blood to Mild Cognitive Impairment (MCI), and research shows that elevations in inflammatory markers may be present decades before any AD symptoms appear.

However, whether markers of inflammation in the blood (i.e., ‘peripheral’ inflammation) were related to known measures of AD-related pathology, even after accounting for CSF levels of inflammation (i.e., ‘central’ inflammation), remained unclear. Researchers also wanted to know whether markers of inflammation in blood plasma reflected inflammation of the central nervous system.

“One of the two primary goals of our study was to assess the association between inflammatory markers in CSF and plasma to clarify how well plasma inflammatory markers reflect central nervous system inflammation,” said study author Brianne Bettcher, PhD, assistant professor of neurosurgery and neurology at the University of Colorado School of Medicine. “Even more importantly, we were interested in determining whether inflammatory markers in plasma were independently linked to CSF markers of AD-related pathology and neuronal damage in a group of healthy, community dwelling older adults.”

Her team tested blood and CSF samples from 173 middle-aged and older adults enrolled in the Wisconsin Alzheimer’s Disease Research Center. Participants were healthy adults in that they had no clinical symptoms of Alzheimer’s disease, although some had family histories of dementia presumed due to AD.

The scientists had expected inflammation markers in the CSF to be more robust predictors of AD-related pathology and neuronal damage than those in the blood due to the `blood brain barrier.’

“Results from our study suggest that although CSF markers of inflammation are strong predictors, both plasma and CSF markers of inflammation independently relay information about AD-related pathology and neuronal damage in head-to-head comparisons,” Bettcher said.

The finding was unexpected.

“From my perspective, there has been a perception in the field that the blood and the ‘periphery’ are not related to the brain – that the brain and the rest of the body are completely separate,” Bettcher said. “I think increasing evidence suggests that the brain and body communicate. Our study shows that inflammation markers in the blood may be telling us about what is going on inside the brain.”

Recent animal studies have shown a strong relationship between elevated inflammation and the propagation of tau proteins, which are associated with AD.

Bettcher said the new findings could possibly serve as the focus of more in-depth studies aimed at developing a blood test to detect inflammation biomarkers years before symptoms of Alzheimer’s appear.

She says the study also points to a potentially early role for inflammation in aging and AD. Bettcher also emphasized that although participants had detectable levels of AD-related markers and markers of neuronal damage in their CSF, the presence of these markers alone does not indicate a diagnosis of AD, nor does it mean that they will develop AD in the future.

“These findings add to a growing body of literature underscoring an increasingly important relationship between systemic inflammation, central inflammation, and pathological outcomes,” she said.

Full Reference:
Bettcher, B.M., Johnson, S.C., Fitch, R., Casaletto, K.B., Heffernan, K.S., Asthana, S., Zetterberg, H., Blennow, K., Carlsson, C.M., Neuhaus, J., Bendlin, B.B., & Kramer, J.H. (2018). Cerebrospinal fluid and plasma levels of inflammation differentially relate to CNS markers of Alzheimer’s disease pathology and neuronal damage. Journal of Alzheimer’s Disease, 62(1). DOI 10.3233/JAD-170602

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Curiosity: It’s what makes new interim vice chancellor tick

Robert Eckel at desk
Dr. Robert “Bob” Eckel is serving as interim vice chancellor for research while a search for a permanent replacement is underway. Eckel has served as program director of the Clinical Translational Research Center Network of the Colorado Clinical Translational Sciences Institute (CCTSI) and the CU Adult General Clinical Research Center. He was only the second endocrinologist ever to serve as president of the American Heart Association.

It might have been what killed the cat, but to Dr. Robert “Bob” Eckel, the University of Colorado’s new interim vice chancellor for research, curiosity reigns in propelling a successful career and research program.

“It’s what drives the bus here,” said Eckel, MD, recently tapped for the job left vacant by Dr. Richard “Dick” Traystman’s death this fall, as CU administrators launch a search for a permanent vice chancellor.

Although “filling Dick’s shoes is impossible,” Eckel, an international expert in his field of lipid and lipoprotein metabolism and a recognized face on the CU Anschutz Medical Campus after nearly 40 years, said he hopes his ingrained curiosity can serve as a catalyst for furthering the research enterprise at an institution that has been good to him and his profession.

“There are many components to a successful career in science and medicine,” Eckel said. “But curiosity, in my opinion, is one of the most important factors. If curiosity is driving you, then grants, papers and quality research will follow.”

Fanning the curiosity flame

The curiosity flame was lit early in Eckel’s career. After conceding that he was no Vivaldi and ditching the thought of a profession in music (a passion that led him to his first wife, a talented violinist), Eckel decided his idea of medical school was more on track. “And I knew it would make my mother happier.”

But his vision of being solely a clinically-focused doctor soon vanished. “I found out during my residency in internal medicine that I was starting to get increasingly curious about what made people sick and why they weren’t responding to therapy,” said Eckel, an endocrinologist in both the School of Medicine’s Division of Endocrinology, Metabolism and Diabetes and Division of Cardiology. He also has an appointment in the Department of Physiology and Biophysics.

“I thought if I wanted to pursue that drive, that ultimately I needed to be trained in research,” said Eckel, crediting his subsequent research-fellowship experience at the University of Washington for fanning the flames. “I came out on fire for research.”

‘There are many components to a successful career in science and medicine. But curiosity, in my opinion, is one of the most important factors. If curiosity is driving you, then grants, papers and quality research will follow.’ – Robert Eckel, MD

Bringing a dual perspective

Eckel, who often calls himself a “cross-dresser” as a preventive cardiologist and endocrinologist, said he loves all components of his job. “As a clinician, I’m more of a preventive cardiologist, but as a scientist, I’m a metabolically-driven guy,” he said, adding that his physician-scientist perspective brings a different “twist” to the vice chancellor position.

As an investigator, Eckel thrives on being tucked in his lab, where he and Assistant Research Professor Kimberley Bruce, PhD, have expanded their longtime focus on how lipids (such as cholesterol and triglycerides) and lipoproteins (which carry lipids) relate to obesity, metabolic syndrome, diabetes and cardiovascular disease.

The two have joined forces with Wendy Macklin, PhD, a leading expert on glial biology in the Department of Cell and Developmental Biology, in investigating how lipids and lipoproteins play a role in neurological disorders, such as Multiple Sclerosis and Alzheimer’s disease, with a renewed funding award on Feb. 1.

“Myelin is loaded with lipids,” Eckel said, referring to the myelin sheath that protects the body’s nervous system. With MS, a disabling degenerative disease that affects an estimated 400,000 Americans, myelin is slowly destroyed. “So we are involved in understanding how lipids and lipoproteins can be processed to re-myelinate nerves that have been demyelinated.”

Eckel and wife at Nuggets game
Dr. Robert Eckel poses with Rocky and wife, Margaret, at a Nuggets game. Eckel credits the women in his life for much of his success.

Encouraging research partnerships

Bruce and Eckel have also teamed up with another top CU Anschutz Medical Campus researcher, SOM’s Department of Neurology’s Huntington Potter, PhD, in their work on the role of lipids and lipoproteins and the brain-degenerating Alzheimer’s disease. Alzheimer’s affects at least 5.5 million Americans, a number expected to soar with an aging population.

During her years working beside him, Bruce said Eckel has served as a great mentor and role model. “I’ve learned a great deal from Bob, not just about lipid and lipoprotein biology, but also about how to strive for scientific excellence while still keeping your feet on the ground,” she said. “I honestly can’t think of anyone better for this vice chancellor role.”

No stranger to cross-disciplinary collaboration, Eckel said researcher success also depends on networking. “None of us is an island anymore in science and medicine. There are no single-authored papers anymore. Science is really teamwork, and that’s something I will consider as I look at the big network of research on both campuses.”

Recognizing research’s influence

Eckel, winner of the Endocrine Society’s 2016 Outstanding Clinical Investigator Award, understands the power of research on both a professional and a personal level.

Diagnosed at age 5 with Type 1 diabetes, a disease he shares with two sons and opted early on to separate from his lab work, Eckel said he’s grateful for his colleagues who have made huge research strides in the insulin-related disorder.

“There’s been so much improvement in therapeutics for Type 1 diabetes,” he said. “I have a pump and a sensor,” he said, patting his lower chest, where a pump automatically infuses the insulin his body cannot make. “I’ve had this disease for 65 years now, and I’ve never felt better in my life. I feel fortunate to be alive, and that’s research,” he said.

Finding collaboration on all fronts

Eckel with family
Dr. Robert Eckel balances career and family, which includes three grandchildren and five grown children. Eckel, who emphasizes the importance of music in a well-rounded lifestyle, taught each of his kids piano until they were in sixth grade.

Eckel doesn’t just stand out in his field. In 2016, he won Father of the Year from the American Diabetes Association, for which he serves on the board. A devoted but humble family man, he doesn’t take the credit for his well-rounded success.

“It’s the women I’ve done it all with,” he said, acknowledging his first wife, who worked as a teacher while he went through medical school and then raised their five children before she died of breast cancer at age 45. “She was a great mom.”

Eckel eventually married his current wife, Margaret. “She stepped up and became a stepmom who’s now loved by all of my kids, and I’ve been married to her almost as long as I was my first wife. So I had great companionship and love from two women, and I probably didn’t deserve either one of them.”

On the professional side, Eckel said Bruce “runs the bus” in his research lab. “She’s smarter than I am. I’m lucky to have her.” With a retirement date set for July 1, 2019, Eckel hopes to have his research program ready to hand over to Bruce and to have fulfilled his new interim post to the best of his ability.

“I work at a great institution that’s been incredibly supportive, and it’s a privilege to serve,” said Eckel, who will not vie for the permanent post. “But right now, I’m neither intellectually nor emotionally ready to retire. The science is just too much fun.”

 

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Rare brain donation could shed light on Alzheimer’s pathology

As he looks back on this year’s activities at the Rocky Mountain Alzheimer’s Disease Center, Huntington Potter, PhD, points to one event that was especially meaningful – receiving the center’s first brain donation for research from a person with Down syndrome who died with late-stage Alzheimer’s disease.

It’s a contribution neuroscience researchers hope will help further unravel the mystery of why some people develop Alzheimer’s disease symptoms while others do not.

Potter, whose groundbreaking research expanded knowledge of the genetic and molecular relationships between Alzheimer’s disease and Down syndrome, said the donation was made by a Denver-based family who felt that their sister would have been thrilled to know that she was making a significant contribution to science.

‘Great contribution’

And, Potter said, it’s a sentiment that goes beyond this one family. “People with Down syndrome and their families would very much like to help research to understand Alzheimer’s disease in them and in the rest of us, and so brain donations from people with Down syndrome are very important.”

“It’s a great contribution to humanity,” he added.

Potter plays multiple roles related to Alzheimer’s disease and Down syndrome research at the CU School of Medicine. In addition to being the Director of the Rocky Mountain Alzheimer’s Disease Center, he is also the Director of Alzheimer’s Disease Research at the Linda Crnic Institute for Down Syndrome.

The brain came from a 63-year-old woman named Gretchen Josephson, whose family has a long lineage in medicine and a connection to the CU School of Medicine. (See sidebar below).

Connection to Alzheimer’s disease

The direct link between Down syndrome and Alzheimer’s disease is on human Chromosome 21. People with Down syndrome are born with three copies of Chromosome 21 in every cell, a condition that occurs at conception.

Brain donor Gretchen Josephson
The brain donation came from Gretchen Josephson, second from left, a woman with Down syndrome. Josephson’s family has a long lineage in medicine. Here, she is pictured with her three sisters.

Additionally, the main gene that produces the protein linked to Alzheimer’s disease resides on Chromosome 21. Because people with Down syndrome have this third copy of Chromosome 21 in all of their cells, Potter says that they all will develop the underlying Alzheimer’s disease pathology by the time they are 40 years old.

According to Potter, the mystery is that despite all people with Down syndrome having this predisposition to Alzheimer’s disease brain pathology, around 20 percent will not develop dementia symptoms.

“We’d like to study them to better understand how Alzheimer’s disease brain pathology and dementia develop,” he said. “That way, we could learn who is most likely to develop dementia and who isn’t. And we’d like to be able to initiate treatment for people who don’t have Down syndrome but who might be at risk, say, in their 40s or 50s, and prevent the cell death and the problems that accompany Alzheimer’s disease.”

Potter points out that Alzheimer’s disease is believed to start developing as many as 20 years before clinical symptoms appear. He says the main research goal is to develop treatments for people “on the steps” to Alzheimer’s disease, and also to develop early diagnoses.

The vast majority of people who are diagnosed with typical age-related Alzheimer’s disease, over 95 percent, do not have Down syndrome. However, Potter’s earlier research showed that they have Down syndrome-like cells with three copies of Chromosome 21 throughout their bodies, including in neurons in their brains.

Insights into the pathology

“What are the earliest signals in people with Down syndrome that they’re going to develop Alzheimer’s disease within five or 10 years? Can we use those same signals, whether it be a blood protein or a neuropsychological test, to help figure out when and whether the rest of us are at risk for Alzheimer’s disease?”

In recent years, Alzheimer’s disease research centers around the world have received many brain donations from typical people with Alzheimer’s disease, but not from people with Down syndrome. These donations are very rare, and “are very valuable,” said Potter, “because if we can understand more about the pathology that develops in people with Down syndrome, we will be better able to understand the pathology that happens in typical people. And that’s going to give us a hint of what’s going wrong, and of how we might be able to compare the brains and come up with an idea for fixing them.”

Potter also notes that receiving a brain for research from a person with Down syndrome who did not have dementia at death would be especially rare and would be extremely valuable for research.

Potter encourages adults with Down syndrome to be assessed by the neurology team in the Memory Disorders Clinic, part of the Neurology clinic in the Anschutz Outpatient Pavilion and the clinical arm of the Rocky Mountain Alzheimer’s Disease Center. “We recommend this regardless of whether they have memory problems, so that they can take full advantage of the consultation opportunities,” he said.

More information about the center is at www.medschool.ucdenver.edu/alzheimers.

Guest Contributor: Both of these stories were written by Helen Gray, MBA, Communications and Community Outreach Coordinator of the Rocky Mountain Alzheimer’s Disease Center.

 

GRETCHEN JOSEPHSON MADE A ‘LAST GREAT GIFT TO ALL OF US’

The Denver woman with Down syndrome whose brain is the first donated for Alzheimer’s disease and Down syndrome research had a reputation for making her own way in the world and for making friends wherever she went.

Gretchen Josephson, who was 63 when she died, was the daughter of two physicians, the fourth of four girls. Her mother, Lula Lubchenco Josephson, MD, was a professor in the Department of Pediatrics in the CU School of Medicine. Her father, Carl Josephson, MD, was a cardiologist in private practice.

Gretchen graduated from South High in Denver Public Schools and studied food service at the Emily Griffith Opportunity School. The training helped her land a job as a bus girl at the Tea Room at the old downtown Denver Dry Goods store before it closed. Gretchen was retrained to work with inventory on the retail side of Foley’s, and then Macy’s at the Cherry Creek Mall. By the time she retired, Gretchen had worked continuously for 37 years.

And customers remembered Gretchen. Her eldest sister, Patty McFeeley, MD, said “you couldn’t walk with her through the Cherry Creek Mall without someone stopping her and saying, ‘Hi Gretchen.’”

Wrote a book of poetry

Gretchen wrote poetry. In 1997, with her mother’s encouragement, she published a book of poems called “Bus Girl,” and read and signed copies for a packed house at the Tattered Cover bookstore.

Gretchen Josephson with book of poetry
Gretchen Josephson holds “Bus Girl,” her book of poems.

One of Gretchen’s passions was country music. She frequently traveled to Nashville and figured out how to go backstage at concerts. The walls of Gretchen’s apartment were covered with photos of her and the stars she adored so much.

Another passion was sports. In addition to skiing, Gretchen swam and competed in Special Olympics. Her family took her on scuba trips, and her sister said she especially loved the shipwreck dives.

Self-advocate for Down syndrome

Gretchen was a self-advocate for Down syndrome, and she spoke at numerous national and international conferences, telling large audiences about her personal experiences with independent living.

McFeeley, a pathologist, said it was natural for Gretchen’s sisters to consider making the brain donation for scientific research. She occasionally took Gretchen along when she performed post-mortem examinations on cadavers, and Gretchen was, according to McFeeley, “fascinated” with the procedure.

Although Gretchen’s Alzheimer’s disease had advanced so much that she wasn’t able to discuss her own brain donation before she died, her sisters firmly believe that would have been what Gretchen wanted. “It was her last great gift to all of us,” said McFeeley.

 

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CU Anschutz Researcher Receives Alzheimer’s Association Grant

The Alzheimer’s Association, in partnership with a fundraising initiative led by philanthropist Michaela “Mikey” Hoag, announces a new $7 million investment in clinical trials that target brain inflammation as an innovative avenue for Alzheimer’s disease therapy. Among the four clinical trials included in the newly-funded research is one led by noted Alzheimer’s researcher Huntington Potter, Ph.D., of the University of Colorado Anschutz Medical Campus.

The Part the Cloud Challenge on Neuroinflammation targets a critical gap in understanding and treating Alzheimer’s, and absorbs some of the financial risk associated with advancing these studies across a space in drug development where many promising ideas stall due to lack of funding. This innovative funding program is the vision of Mikey Hoag, of Atherton, California, whose family is affected by Alzheimer’s disease.

“When my father passed away with Alzheimer’s, I decided to use my personal story to rally others in support of Alzheimer’s research. When my mother started to show signs of the disease, I knew I had to kick these efforts into high gear,” said Hoag. “We hope the competition we’re creating for additional funding will speed the rate of discovery and deliver a new and effective treatment or prevention strategy to doctors’ offices and people’s medicine cabinets more quickly.”

Each study will receive $1 million to advance current research to the next stage of clinical trials. A unique, goal-driven competition offers an additional $3 million to the clinical trial that demonstrates the most promise for treating this devastating disease.

“The importance of the Part the Cloud Challenge from the Alzheimer’s Association cannot be overstated,” said Dr. Potter, who is director of the Rocky Mountain Alzheimer’s Disease Center and professor and director of Alzheimer’s disease research, Department of Neurology, Linda Crnic Institute for Down Syndrome, University of Colorado School of Medicine. “The million dollars, with a potential for another $3 million after two years, will certainly propel novel research forward towards a therapy for Alzheimer’s. For my research, the hope is that Leukine, an FDA-approved drug, may slow or even prevent the progression of Alzheimer’s disease.  That would be a home run for everyone.”

“There has not been a genuinely new Alzheimer’s drug in more than a decade, and there is currently no drug that stops or slows the progression of this devastating disease,” said Linda Mitchell, president and CEO of the Alzheimer’s Association of Colorado. “The Association’s Part the Cloud Challenge is a much-needed and inventive approach to complement mainstream drug development that we hope can change the current situation.”

Increasing evidence suggests neuroinflammation plays an important role in the brain changes that occur in Alzheimer’s and other neurodegenerative diseases. By further understanding the role and the timing of neuroinflammation and immune responses, there is an opportunity to further accelerate novel candidate Alzheimer’s therapies.

Inflammation is a natural immune system response to infection and injury where defense cells are directed to fight infection or repair damaged tissue. However, persistent or misdirected inflammation can damage otherwise healthy tissue, such as the destruction of joint cartilage that occurs in arthritis or nerve damage in multiple sclerosis. Similarly, inflammation in the brain may help protect it from harm, such as the formation of the hallmark amyloid plaques of Alzheimer’s, but too much inflammation may damage the brain’s delicate nerve cells and intricate connections.

The four selected projects will receive $1 million over two years for either a Phase I or Phase II trial. Projects will be evaluated for their ability to advance in human testing, such as being safe for use in people and the ability to influence the underlying biological process they are meant to target. The project that demonstrates the most viable translation to advanced clinical trials will be eligible to receive an additional award of up to $3 million to further therapy development. Three of the four studies are testing potential therapies developed for other conditions that are being repurposed for Alzheimer’s.

“This funding from the Alzheimer’s Association is a testament to the incredible potential that Dr. Potter’s work holds for the future,” said CU Anschutz Medical Campus Chancellor Donald M. Elliman, Jr. “As the director of the Rocky Mountain Alzheimer’s Disease Center, he is ideally positioned to bring together teams of the brightest minds in medicine across the University of Colorado system to unravel the mysteries of Alzheimer’s disease. This generous investment will accelerate Dr. Potter’s work, bringing us closer to novel therapies that could impact countless lives in Colorado and around the world.”

“I like to think we have the brightest, most hard working scientists who also have huge hearts for our families,” said Michelle Sie Whitten, president and CEO of the Global Down Syndrome Foundation – an affiliate of the Linda Crnic Institute for Down Syndrome. “We are so pleased Dr. Potter has received $1 million from the Alzheimer’s Association to advance his research.  His work is shining a light on the link between Down syndrome and Alzheimer’s disease, and his team is focused on several innovative paths towards better treating and preventing Alzheimer’s.”

The funded projects are:

  • A Phase II clinical trial of the FDA-approved drug Leukine, to determine whether it is safe and can help slow or prevent the progression of Alzheimer’s, led by Huntington Potter, Ph.D., Professor and Director of Alzheimer’s disease research, Department of Neurology, Linda Crnic Institute for Down syndrome, University of Colorado Anschutz Medical Campus. Leukine is approved for reducing and preventing infection in people who have received chemotherapy.
  • A Phase II clinical trial to determine if the drug Sativex, a cannabis-based liquid medication that was previously tested for the alleviation of cancer-related pain, reduces brain inflammation and helps slow the progression to Alzheimer’s disease in people with mild cognitive impairment, led by Isidro Ferrer, M.D., Ph.D., Coordinator of the group Neuropathology at CIBERNED (Network Center for Biomedical Research in Neurodegenerative Diseases), Institute of Health Carlos III, Barcelona, Spain.
  • A study to test if treatment with the drug Senicapoc can reduce brain inflammation, alter the rate of brain amyloid accumulation, and improve memory in people with early Alzheimer’s disease or mild cognitive impairment. In previous research, a drug similar to Senicapoc helped to reduce brain inflammation, prevent nerve cell damage, and improve memory in mice with an Alzheimer’s-like condition. The project includes a Phase II clinical trial led by John Olichney, M.D., Professor and Neurologist at the University of California, Davis. Senicapoc has been shown to be safe in clinical trials of sickle cell anemia and asthma, but has yet to be tested in people with Alzheimer’s.
  • A Phase I clinical trial to examine the safety and efficacy to reduce brain inflammation of a novel therapy manufactured by Longeveron LLC using stem cells derived from healthy adult donors and that are delivered into the bloodstream of people with mild Alzheimer’s disease. Anthony Oliva, Ph.D., senior scientist at Longeveron, will serve as principal investigator, and Bernard Baumel, M.D., will serve as the clinical investigator of the trial at the University of Miami Miller School of Medicine. Longeveron is a life sciences company located in Miami, Florida. In past research, this type of stem cell has demonstrated the ability to target and reduce inflammation, promote tissue repair, and improve brain function in mouse models of Alzheimer’s disease.

Individuals interested in applying to participate in the research should register for the Alzheimer’s Association’s TrialMatch program or call the Association’s 24/7 Helpline at 800-272-3900.

 

 

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Key brain receptor sheds light on neurological conditions

Researchers at the University of Colorado Anschutz Medical Campus have found that a key receptor in the brain, once thought to only strengthen synapses, can also weaken them, offering new insights into the mechanisms driving depression, drug addiction and even Alzheimer’s disease.

Weakening or strengthening a synapse can have major implications both good and bad. Strengthening can sometimes be beneficial in treating Alzheimer’s while at the same time causing drug addiction and contributing to Post Traumatic Stress Disorder (PTSD) in other cases.

MDellAcqua.png

Professor Mark Dell’Acqua, PhD, vice-chair of the Dept. of Pharmacology at the University of Colorado School of Medicine.

For years, scientists believed that a special calcium permeable subtype of AMPA-type glutamate receptor only strengthened synapses, which send signals between brain cells. But Professor Mark Dell’Acqua, PhD, vice-chair of the Dept. of Pharmacology at the University of Colorado School of Medicine, and his team of researchers found that it also weakened synapses.

“It is a major and unexpected finding,” Dell’Acqua said. “If these receptors go to synapses for a short time they can promote weakening of those synapses. But if they stick around longer they can strengthen those synapses.  In both cases, that strengthening or weakening can be undesirable if it goes too far in either direction such as in PTSD and drug addiction versus Alzheimer’s.”

Researcher hope that drugs could be manufactured to strengthen or weaken these synapses, depending on the condition being treated.

“Our study broadens our knowledge of the role these calcium permeable AMPA receptors plays in weakening synapses,” Dell’Acqua said. “We are also exploring how these same signaling mechanisms may be relevant to what happens to synapses in Alzheimer’s disease. In that case, synapses may be weakened too much.”

Dell’Acqua said tracking calcium permeable AMPA receptor activity “is important for understanding basic synaptic processes that underlie normal learning and memory and are altered by diseases impacting brain function.”

The discovery, he said, has implications for our understanding of autism, Alzheimer’s, epilepsy, Down syndrome, schizophrenia, PTSD and drug addiction. And it offers new avenues to pursue in treating those conditions.

The study was published in the latest edition of the journal `Neuron.’

The study co-authors include Jennifer L. Sanderson, PhD, and Jessica A. Gorski, PhD.

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