Eliezer Masliah, MD, Director of NIA’s Division of Neuroscience visits Penn

EliezerMasliah_Flyer5217On Tuesday, May 2, 2017, Eliezer Masliah, MD*, Director of the National Institute on Aging’s (NIA) Division of Neuroscience, paid a visit to the University of Pennsylvania’s Institute on Aging (IOA), Center for Neurodegenerative Disease Research (CNDR), and Penn Neurodegeneration Genomics Center (PNGC).

The reason for Dr. Masliah’s visit was not just to learn about the neurodegenerative disease and aging-related research that is taking place in these centers here at Penn, but also to see how they all collaborate and work toward mutual goals. This gave him the opportunity to see firsthand how NIA and National Institutes of Health (NIH) funding is being used and made worthwhile to support the groundbreaking work of these centers.

Several topics were covered during the visit including the inception and mission of the new Penn Neurodegeneration Genomics Center (PNGC), directed by Gerard D. Schellenberg, PhD, and its five NIH-funded projects, the Alzheimer’s Disease Genetics Consortium (ADGC), Alzheimer’s Disease Sequencing Project (ADSP), Consortium for Alzheimer’s Sequence Analysis (CASA), Center for Genetics and Genomics of Alzheimer’s Disease (CGAD), and the NIA Genetics of Alzheimer’s Disease Data Storage Site (NIAGADS). Dr. Schellenberg and other PNGC members, including co-director Li-San Wang, PhD, associate professor of Pathology and Laboratory Medicine and principal investigator of NIAGADS, presented some of the current work and future plans for PNGC to achieve their overarching goal to “completely resolve the genetics of Alzheimer’s disease.”

After the morning session, Dr. Masliah joined John Q. Trojanowski, MD, PhD, Director of the IOA, and Virginia M.-Y. Lee, PhD, Director of CNDR, with several of their lab members as well as several Penn faculty working in neurodegeneration, for an open discussion on the multidisciplinary approach of the IOA and CNDR. A key feature of these centers is their ability to collaborate across many different disciplines within the University of Pennsylvania’s Perelman School of Medicine. This includes faculty members from several different departments such as Pathology and Laboratory Medicine, Neurology, Psychiatry, Geriatric Medicine, and Epidemiology to name a few.

Among the many topics discussed, one that was of particular interest to Dr. Masliah was the large number of young investigators and finding out what it was that attracted them to Penn. Many of the lab members were eager to participate and to share their outlook on why Penn was the right place to start their research career. Overall, they agreed that the collaborative, multidisciplinary nature of these centers is what appealed to them most. They also praised Penn for its training and the encouraging environment that it provides for applying for research grants and other funding opportunities. Additionally, Penn is well known for its state of the art databases and data sharing, providing top-notch integration and access to resources for its investigators. Dr. Masliah was especially impressed with CNDR’s Integrative Neurodegenerative Disease Database (INDD) which tracks nearly 17,000 patients and/or research subjects at Penn’s several neurodegenerative disease related centers.

The visit concluded with a lecture by Dr. Masliah, titled “Advancing the National Plan to Address AD through National and International Collaborations.” During his talk, Dr. Masliah discussed the recent $2 billion NIH budget increase which includes $400 million new Alzheimer’s disease funds, new NINDS funding opportunities in partnership with NIA on Lewy body dementia (LDB), and the 17 new Alzheimer’s disease FOA’s.

In terms of what to expect for the future, Dr. Masliah says to stay tuned for changes in pay-lines for FY17, more funding for fellowship and K awards, and more funded FOA’s and 27 new FOA’s.


* In his position as the Director of the NIA’s Division of Neuroscience, Dr. Masliah oversees the world’s largest research program on Alzheimer’s disease-related dementias and cognitive aging. He is an internationally renowned neuroscientist and neuropathologist and has approximately 800 original research articles and 70 book chapters. 

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.

First Phase of REACT! Trial Comes to a Close

100_0699The University of Pennsylvania recently wrapped up the first round of its Rhythm Experience and Africana Culture Trial (REACT!), a three-year pilot grant in collaboration with the University of Pittsburgh and supported by the Alzheimer’s Association.

Participants and their guests were invited to the ending ceremony, hosted by the Institute on Aging, which included dance performances, presentations, and art displays showcasing the work that was done throughout the study.

For this trial, participants (ages 60-80) were sorted into one of two activities – an African dance group or an educational/discussion group – to compare the bene ts. Final results are still pending, but are anticipated to reveal whether or not brain health, fitness levels or quality of life improved as a result of participating in the dance or educational activities three times per week for six months.

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To learn more about REACT! visit: www.med.upenn.edu/aging/react.html

Penn’s CNDR celebrates 25 years of groundbreaking research with the supporters and friends who make it all possible

screen-shot-2016-11-08-at-3-01-13-pmThis year, the Center for Neurodegenerative Disease Research is celebrating its 25th anniversary in a big way. Penn Medicine organized an intimate anniversary event generously hosted by longtime supporters and friends of CNDR, Bob Lane, 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 groundbreaking 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, CNDR researchers, IOA EAB members, supporters of the Center and close friends of the hosts.

Stay tuned for our special edition CNDR 25th Anniversary Newsletter coming early next year.

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