CNDR Celebrates 25 Years of Groundbreaking Research

This year, Penn’s Center for Neurodegenerative Disease Research (CNDR) is celebrating 25 years of groundbreaking research.

Celebrating 25 Years

In honor of this milestone, Penn Medicine organized an intimate anniversary event generously hosted by longtime supporters and friends of CNDR, Bob Lane, who is also an Institute on Aging External Advisory Board (IOA EAB) member, and his wife, Randi Zemsky, at their home in the Rittenhouse Square section of Philadelphia.

The event celebrated the work of CNDR over the past 25 years and highlighted research breakthroughs still on the horizon. It was also an opportunity to bring together and thank many of the Center’s supporters. The event was attended by David B. Roth, MD, PhD, Chair of the Department of Pathology and Laboratory Medicine at the University of Pennsylvania, CNDR researchers, IOA EAB members, supporters of the Center and close friends of the hosts.

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The History

— from “A Conversation with Drs. Lee and Trojanowski,” an article by Lisa Bain featured in the CNDR 25th Anniversary special edition newsletter (page 3) — 

Some twenty-five years ago when John Q. Trojanowski, MD, PhD, first envisioned a Center for Neurodegenerative Disease Research (CNDR), Virginia M.-Y. Lee, PhD, MBA, saw only the additional paperwork that would be required. Since they were both already well established in the field, she thought, “what do we need a center for?” But he convinced her that branding and identifying CNDR as a common locus for studies of Alzheimer’s (AD) and Parkinson’s (PD) disease as well as Frontotemporal lobar degeneration (FTLD) and Amyotrophic lateral sclerosis (ALS) or Lou Gehrig’s disease was very important to pursue; and they both knew that the mission — to find cures for these neurodegenerative diseases — was not something that they alone could solve.

They would need a team, infrastructure, an environment that would be welcoming to a multidisciplinary group of collaborators (see Figure 1) and of course, funding. “And that is the dream for CNDR that has come true,” said Trojanowski.

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Get the full story of CNDR’s history, mission, research, and programs in the 25th Anniversary special edition newsletter here:

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CNDR’s Annual Marian S. Ware Research Retreat Through the Years

Each year, CNDR hosts its annual Marian S. Ware Research Retreat to highlight any current or groundbreaking discoveries at CNDR and in the field of neurodegenerative disease research at large. Since the first event in 2000, CNDR has covered a variety of themes from genetics to training the next generation of scientists. Stay tuned for information on CNDR’s 2017 Research Retreat, but for now, take a look back at some of the topics covered in the past:

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You can also view an interactive timeline, including lists of past Retreat speakers, here!
(view in 3D mode for best experience)

Learn more about CNDR at: www.med.upenn.edu/cndr

 

 

Can postponing ill-health via comprehensive damage repair extend human lifespan indefinitely?

On Tuesday, December 6, 2016, the Institute on Aging (IOA) welcomed Aubrey de Grey, PhD, Chief Science Officer at the SENS Research Foundation, for a Visiting Scholars Series lecture on “Rejuvenation biotechnology: Postponing ill-health via comprehensive damage repair.”

The SENS Research Foundation is a public charity doing biomedical research with a focus on developing new medicines that may be more effective than current methods in postponing the ill health of old age.

“I do think that the general concept of eliminating damage that the body does to itself is something in which the sky is the limit,” said Dr. de Grey.

He compared this idea to the example of restoring vintage cars. He explained that since we are able to keep cars going essentially forever just by periodic and comprehensive preventative maintenance, we should be able to do the same thing for the human body, ultimately maintaining people in “truly youthful health indefinitely.”

While he does recognize that the human body is much more complex, Dr. de Grey believes that “the further we get in the process of developing methods for eliminating the various types of damage that the body does to itself, the more slowly we will accumulate damage because we will only be left with the residual damage that we haven’t yet worked out how to fix.”

Watch Dr. de Grey’s full lecture here!

New “Human-like” Animal Model Better Mirrors Tangles in Alzheimer’s Disease Brains

virginialee-inlabResearchers at the University of Pennsylvania’s Center for Neurodegenerative Disease Research (CNDR) have developed a new mouse model to better replicate the neurofibrillary tangles that form in the brains of patients with Alzheimer’s disease (AD).

In the video below, Virginia M.-Y. Lee, PhD, MBA, Director of CNDR and senior author of the study, explains that until now, researchers have been using synthetic tau tangles made in the lab — engineering mice to overexpress the tau proteins in order for the tangles to form. The new study instead uses authentic tangles taken from Alzheimer’s brains and injected into normal mice to provide a more accurate model not only of the properties in AD brains, but also how the disease spreads over time.

These findings are especially important in terms of moving forward with developing potential treatments for Alzheimer’s disease. “It is essential for us to have animal models so we can use them to test the efficacy of potential treatments before they go into humans,” said Dr. Lee.

This study was published in the Journal of Experimental Medicine and featured by ALN.

Penn Medicine News Release.

The Longevity Dividend

On Tuesday, November 29, 2016, the Institute on Aging hosted its annual Vincent J. Cristofalo Lectureship and reception featuring this year’s keynote speaker, S. Jay Olshansky, PhD, professor of public health at the University of Illinois at Chicago.

Dr. Olshansky’s research focuses primarily on human longevity, exploring the health and public policy implications associated with individual and population aging, global implications of the re-emergence of infectious and parasitic diseases, and most recently, the topic of his Cristofalo Lecture; the pursuit of the scientific means to slow aging in people, or as he calls it “The Longevity Dividend.”

“The Longevity Dividend,” a term borrowed from the era of the “peace dividend,” is basically the idea that if we can find a way to slow the basic biological aging process, both society and individuals will reap huge economic and health benefits.

Over the years, human life expectancy has become longer but the success of extended lifespans come with a price. With the ridding of many infectious diseases came the rise of other conditions such as cardiovascular disease, cancer, and Alzheimer’s disease; three different diseases with one thing in common—the process of aging being their most powerful risk factor.

“The rise of these diseases are nota consequence of failure… they are a consequence of success. You’ve lived long enough to experience them. But, the consequences of success might be very dangerous.” – S. Jay Olshansky, PhD

Dr. Olshanksy shared more on the “longevity dividend” during our video interview here:

In addition to his current research on “The Longevity Dividend,” Dr. Olshansky and his colleagues have also conducted research on “facial analytics” combined with biodemography. The study of facial analytics uses components of the face to measure disease risk, longevity risk, and survival prospects. Through this research, Dr. Olshansky and his team are trying to find new ways of allowing organizations and industries to use what we know about ourselves to improve the ways that they do assessments of health and survival.

Recently, Dr. Olshansky and his colleagues published an article in Computer that lays out the framework for building a “health data economy.”

“I think a new form of “currency” will be developed and this “currency” will be your own health data,” explained Dr. Olshansky. The idea is to take data from Fit Bits and other wearable monitoring devices monetize this information, for instance, selling your recorded health data to companies and organizations in exchange for things like money, lower premiums on health insurance policies, coupons, and more. He believes that this resource could be the new form of collecting health data and could inspire a whole new generation of citizen scientists.

To watch Dr. Olshansky’s full lecture on “The Longevity Dividend,” click here.

To learn more about the Vincent J. Cristofalo lectureship, click here.

CNDR Researcher receives second place prize for poster on Alpha-Synuclein at 2016 Udall Center Directors Meeting

Last month, Chao Peng, a post-doctoral researcher at the University of Pennsylvania’s Center for Neurodegenerative Disease Research, won a second place poster prize at the 2016 Udall Center Directors Annual Meeting.

Title: “Distinct Pathological a-Synuclein Strains in Glial Cytoplasmic Inclusions and Lewy Bodies”
Presenter: Chao Peng
Authors: Chao X. Peng, Ronald Gathagan, Dustin J. Covell, Anna Stieber, Coraima Medellin, John L. Robinson, Bin Zhang, Kelvin C. Luk, John Q. Trojanowski, Virginia M.-Y. Lee

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Chao Peng (second from the right) with Walter Koroshetz, MD, Director of NINDS (far left), and his fellow poster winners at the Udall Center Directors Meeting.

Peng’s poster was on the properties of the misfolded alpha-synuclein protein in different neurodegenerative diseases.

Alpha-synuclein is known for playing a key role in the development of Parkinson’s disease (PD), however, this protein is not unique to PD. Alpha-synuclein is also present in the brains of patients with Lewy body dementia (LBD) and Multiple system atrophy (MSA).

During a video interview with the Institute on Aging (see below), Chao Peng explains that alpha-synuclein accumulation is also present in almost 50% of Alzheimer’s disease cases.

While these diseases all show signs of this same misfolded protein, they actually exhibit very different pathological and clinical behaviors than one would experience with Parkinson’s disease—but how?

Chao Peng and his colleagues at CNDR are using multiple different cell and animal models to better understand not only how this occurs and why the same misfolded protein can cause one disease in one patient but something different in others, but what this could mean for potential treatments. Learn more here:

Eli Lilly Announces Unfortunate Results for Solanezumab Phase III Clinical Trial

Today, global pharmaceutical company, Eli Lilly and Company, revealed the results of their solanezumab study, a phase III clinical trial seeking to combat Alzheimer’s disease (AD). Unfortunately, for both researchers and those affected by Alzheimer’s, the once-promising trial has provided disappointing results.

As reported by NBC News, Eli Lilly released a statement explaining that “patients treated with solanezumab did not experience a statistically significant slowing in cognitive decline compared to patients treated with placebo,” therefore, they will not pursue the study any further.

“The results of the solanezumab EXPEDITION3 trial were not what we had hoped for and we are disappointed for the millions of people waiting for a potential disease-modifying treatment for Alzheimer’s disease. We will evaluate the impact of these results on the development plans for solanezumab and our other Alzheimer’s pipeline assets,” said John Lechleiter, president and chief executive officer of Eli Lilly

Read the full statement from Eli Lilly here.

This news comes just days after news of a dramatic decline in dementia seen among older adults in the U.S. The STAT News article reported that “the percent of older US adults with dementia, including Alzheimer’s disease, declined from 11.6 percent in 2000 to 8.8 percent in 2012, a decrease of nearly a quarter.”

Yet, there is still an estimated 5 million Americans 65 and older currently suffering with Alzheimer’s or other dementias—along with their loved ones and a field of researchers—who are desperately seeking more effective treatments. Until now, many were hopeful that solanezumab might have been the answer that they were looking for.

“The field of treatments for Alzheimer’s disease has been living through a prolonged drought. We’ll soak up the arrival of a new drug like rain on a sun-burnt, fallow field, and solanezumab may be that drug,” said Jason Karlawish, MD, Co-director of Penn Memory Center, in a recent Forbes column highlighting the study.

Developing Breakthrough Treatments for Alzheimer’s Disease

“Alzheimer’s disease (AD) is our #1 public health problem in terms of cost and burden of care and it is projected that over 100 million people will be diagnosed with Alzheimer’s worldwide by 2050,” said Stephen Salloway, MD, MS, a professor of Neurology and Psychiatry at Brown University and the Institute on Aging (IOA) at the University of Pennsylvania’s most recent Visiting Scholar.

On Tuesday, November 15, 2016, Dr. Salloway visited the University of Pennsylvania to present a lecture on “Developing Breakthrough Treatments for Alzheimer’s Disease” in which he shared some of the latest advances, and challenges, in the field of Alzheimer’s disease research.

“Our goal, and the goal of the National Plan developed by the U.S. Congress, is to develop breakthrough treatments by 2025.” – Stephen Salloway, MD, MS

It’s no secret that the world is getting older. In fact, according to Dr. Salloway, there are many regions of the world where more than 30 percent of the population will be 60 or older and coming into the risk state for cognitive impairment. Aside from the staggering and rising cost of care for Alzheimer’s disease and related dementias, it is the disease that older people fear most — fearing the disability and loss of identity.

With this in mind, you would assume that Alzheimer’s research would be a top priority, but “funding for Alzheimer’s disease at a federal level has paled in comparison to other diseases like cancer and heart disease,” said Dr. Salloway. However, things are starting to look up and we have recently started to see some improvement. For the first time, there is a strong potential for Alzheimer’s federal research funding to reach over $1 billion.

Researchers are steadily working to build a worldwide infrastructure to fight Alzheimer’s disease with a number of private/public partnerships, collaborative initiatives such as the Alzheimer’s Disease Neuroimaging Initiative (ADNI) one component of which is right here at Penn, and many other alliances across the board. We’ve already seen several important benefits emerge from these initiatives; for example, real time data sharing to trigger an increase in publications and shape new trials and views on Alzheimer’s research.

Several advances in AD research have been made over the years, from the discovery of plaques and tangles to the development of new imaging techniques and biomarker breakthroughs. “We now know that plaques and tangles begin accumulating 15-20 years before the onset of cognitive decline,” explained Dr. Salloway. Through these findings, we are able to better understand the progression of Alzheimer’s disease as a process starting with a long pre-clinical period, moving on to an early symptomatic period of mild cognitive impairment (MCI), then followed by the actual dementia period. The significance of understanding this process is that it opens the door of opportunity to eventually intervene before a patient reaches the late stage of Alzheimer’s disease.

In terms of current treatments, there are two classes of medications approved to treat the symptoms of the dementia phase of Alzheimer’s disease—cholinesterase inhibitors and memantine. Both drugs have been found to have a very mild multi-symptomatic clinical effect, but cannot cure the disease or stop it from progressing, which is the ultimate aim for researchers.

Since 2003, there have been no new treatments approved by the U.S. Food and Drug Administration (FDA), but there have been several clinical trials focusing on the amyloid pathway — some disappointing and some encouraging.

Two major phase-3 trials were the bapineuzumab trial and the solanuzumab trial. While the bapineuzumab trial was stopped after showing no clinical benefit, the solanuzumab trial raised some hope after findings showed some modest slowing of cognitive decline in a milder subgroup. We are expecting to see some new results soon from a replication trial.

Most recently, some very encouraging results emerged from a phase 1b trial focusing on the antibody, aducanumab. This study showed a substantial dose-dependent lowering of a-beta on amyloid PET scans and also suggested dose-dependent lowering of cognitive decline. There are currently two phase-3 trials underway hoping to reproduce these findings in early Alzheimer’s disease.

“This is very exciting to enter the era of Alzheimer’s prevention, but there are many challenges,” said Dr. Salloway. One of the biggest challenges that researchers face is recruitment of a much larger sample size and population than they’ve used in the past. “In the past, we have tested medicine for people who are cognitively impaired, mostly with dementia, and now we have to reach people who may be at risk for Alzheimer’s in a community who is not coming specifically for care,” he explained. This means they will need hundreds of thousands, if not millions, of people to be enrolled in order to find the highest group at risk and to test medications.

For Dr. Salloway, trying to figure out how to reach and engage this community “is a vastly new undertaking and a second career.” However, he believes that a big avenue is going to be through all types of media—social media, print media, broadcast media, etc.

“The media is critical for getting the word out” – Dr. Salloway

Following the publication and coverage of the results of the aducanumab trial, Dr. Salloway’s center had over 500 calls from people looking to volunteer for research.

In terms of future research, Dr. Salloway has a vision. Through the eventual use of combination treatments and therapies, “Alzheimer’s disease will be much more treatable and manageable than it is today,” he believes.

“Our goal is to detect risk, initiate treatments early, engage the public, develop new public/private partnerships, and to make investments in research to succeed [in fighting Alzheimer’s disease].” – Dr. Salloway  

Dr. Salloway is also the Director of Butler Hospital’s Memory and Aging Center.