“Modeling Neurodegenerative Diseases,” CNDR’s 2017 Marian S. Ware Research Retreat

Screen Shot 2017-11-09 at 1.27.43 PMOn Thursday, October 19, 2017, Penn’s Center for Neurodegenerative Disease Research (CNDR) hosted its annual Marian S. Ware Research Retreat. This year’s topic was “Modeling Neurodegenerative Diseases” and featured a variety of expert speakers within the field.

“As is the tradition with CNDR retreats, every year we focus on a different aspect of neurodegenerative disease. This year, our theme was how to model the complexity of these conditions, for example at the molecular, cellular, and systems levels. The internal and external speakers provided a rich sampling of cutting-edge work being done on each of these areas,” said Kelvin Luk, PhD, Research Assistant Professor of Pathology and Laboratory Medicine and organizer of this year’s CNDR Retreat.

“Among the highlights were the trainee presentations, while we were treated to some spectacular methods for visualizing intact tissues and modeling how disease might be spreading across the central nervous system. Our keynote speaker also finished off by giving a glimpse of the disease process as it advances in living AD patients.

Overall, I think/hope it was enjoyed by all that were present. The feedback was very positive and we were able to bring together many members of the local (Penn and extramural) community from very diverse backgrounds.” – Kelvin Luk, PhD

In addition to the lectures, the day-long event also includes an annual poster session where scientists in all stages of their career, from Penn and beyond, can present their current and recent neurodegenerative-disease related research. The top three posters are selected by experienced judges and are awarded prizes. See this year’s poster winners below!

2017 Marian S. Ware Research Retreat Poster Winners

1st Prize:

Poster Title: “Genome-wide Co-translational Decay of Canonical mRNAs”
Authors: Fadia Ibrahim, Manolis Maragkakis, Panagiotis Alexiou, and Zissimos Mourelatos
Affiliation: University of Pennsylvania Perelman School of Medicine, Department of Pathology and Laboratory Medicine, Division of Neuropathology

2nd Prize:

Poster Title: “Amnestic and Non-Amnestic Phenotypes of Alzheimer’s Disease: An MRI-Based Phasing Analysis”
Authors: Fulvio Da Re1,2,3, Jeffery S Phillips1,4, Laynie Dratch1, Carlo Ferrarese3, David J. Irwin1,4, Corey T. McMillan1,4, Eddie Lee5, Leslie M Shaw5, John Q Trojanowski5, David A Wolk4,6, and Murray Grossman1,4
Affiliation: 1) Penn FTD Center, University of Pennsylvania, 2) PhD Program in Neuroscience, University of MilanoBicocca, Milan, Italy, 3) School of Medicine and Surgery, Milan Center for Neuroscience (NeuroMI), University of MilanoBicocca, Milan, Italy, 4) Perelman School of Medicine, University of Pennsylvania, 5) Center for Neurodegenerative Disease Research, University of Pennsylvania, 6) Penn Memory Center, University of Pennsylvania

3rd Prize:

Poster Title: “Tau and Synuclein: a Tojan horse in the making?”
Authors: Hannah J. Brown, Fares Bassil, Shankar Pattabhiraman, Bin Zhang, Dawn Riddle, John Q. Trojanowski, Virginia M.-Y. Lee
Affiliations: Department of Pathology and Laboratory Medicine, Institute on Aging and Center for Neurodegenerative Disease Research, University of Pennsylvania Perelman School of Medicine

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Full list of 2017 CNDR Retreat Speakers:Screen Shot 2017-11-09 at 1.26.02 PM.

Learn more about CNDR here.

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Penn Medicine’s 6th Annual 5K for the IOA & Memory Mile Walk

It was a warm Fall morning on Sunday, September 24, 2017 as 371 runners and walkers and 70 volunteers gathered for Penn Medicine’s 6th Annual 5K for the IOA and Memory Mile Walk.

The fundraiser, which takes place throughout Penn Park and the University of Pennsylvania campus, raised a total of $49,260 this year for Alzheimer’s and aging-related disease research efforts at Penn’s Institute on Aging.

In addition to its usual run and walk, the event also included pre and post-race yoga sessions, entertainment provided by DeeJay007, and photobooth fun for the whole family. This year’s overall male winner, Alexis Tingan (pictured below, left), finished the race in 17 minutes and 35 seconds, with the overall female winner, Sara McCuaig (pictured below, right), not far behind him with a time of 19 minutes and 24 seconds.

To view the full list of race results, click here.

Last week, CBS Philly interviewed PJ Brennan, MD, Chief Medical Officer at Penn Medicine who created the event in memory of his father who lost his battle with Alzheimer’s disease. “I thought it would be a fun way to get my community here together and bring some attention to the work that the Institute on Aging does and raise some money for this novel research,” said Brennan during the interview.

To view more photos of the event, click here.

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

 

 

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.

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.

Could treating one disease lead to another? The possible link between prostate cancer treatment and dementia

The possible link between prostate cancer treatment and dementia is a topic that has been making quite a few headlines over the last several weeks. According to a recent Penn Medicine News Release that seems to have started the conversation, researchers at the University of Pennsylvania have found that “a common hormone therapy [used] to treat prostate cancer may double a man’s risk of dementia, regardless of his age.”

Last year, lead author Kevin T. Nead, MD, MPhil, a resident in the department of Radiation Oncology at the Perelman School of Medicine at the University of Pennsylvania, and his colleagues discovered an association between Alzheimer’s disease and androgen deprivation therapy (ADT) — a treatment for prostate cancer that is used in over half a million men in the U.S. However, the new findings, published in JAMA Neurology, lead them to believe that the neurocognitive risk involved is actually broader than just Alzheimer’s.

As stated in the news release, “while the findings do not prove that ADT increases the risk of dementia, the analysis comparing the medical records of almost 9,500 prostate cancer patients who received ADT vs. those who did not strongly supports that possibility.”

“We have two papers here showing very similar outcomes and magnitude of risk, which I think supports the case for this to be studied prospectively,” explained Dr. Nead.

This raises the question – do the benefits of ADT outweigh the risk of dementia?

In a recent feature in NY Times Well, Dr. Nead addressed this question explaining that this is a discussion that patients should have with their physician. “This study is important and urges us toward future research, but I don’t think it should impact clinical practice,” he said.

Read the full Penn Medicine News Release here.

Several other local and national news outlets have also picked up the story including