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.

Delirium and Aging

screen-shot-2016-11-10-at-10-41-51-amDelirium, a medical condition characterized by acute confusion, disorientation, or other mental health disruptions that affect thinking and behavior, affects nearly 7 million hospitalized Americans annually. While this condition can occur at any age, it mainly affects individuals 65 years or older and is often misdiagnosed as dementia.

As stated in an article originally published by Kaiser Health News and shared by Next Avenue, “while delirium and dementia can coexist, they are distinctly different illnesses. Dementia develops gradually and worsens progressively, while delirium occurs suddenly and typically fluctuates during the course of a day.” Particularly susceptible patients are those on ventilators or being heavily sedated in intensive care units, as well as those recovering from surgery.

“After an older adult undergoes anesthesia, they can often experience postoperative delirium,” explained Lee A. Fleisher, MD, chair of Anesthesiology and Critical Care at Penn, in a recent Penn Medicine News Blog on postoperative delirium and the uncertainties of anesthesia. “Patients in this state may hallucinate, they may forget why they are in the hospital, or have difficulty communicating or understanding what is going on around them.”

However, delirium can also result from something as simple and easily treated as a urinary tract infection.

According to research published in 2009 and referenced by Next Avenue, an estimated 40% of delirium cases are actually preventable; yet, the underlying cause is still unknown.

With all of this in mind, health care professionals, government agencies, and related nonprofit organizations gathered at the American Society of Anesthesiologists’ Brain Health Summit to discuss, among other topics, the postoperative risks of delirium and delayed cognitive recovery and whether or not they are significant enough to include in consent and patient education materials. They also considered ways to reduce the risks and to increase research funding.

The Penn Medicine News Blog says that “while the Summit provided some direction and tactics for industry leaders to act upon, there are still other options that can be explored and implemented to advance learning, protect patients, and uncover the uncertainties around anesthesia and postoperative delirium.”

“Encouraging patients to follow a balanced diet and exercise regularly in the lead up to surgery, allowing patients to bring mementos and family photos to their hospital room after surgery, even asking families and caregivers to keep a close eye on small declines in patients’ cognitive function preoperatively – simple things like the patient not being as sharp as he or she once were – may help clinicians properly prepare for patient care, and may help patients readjust after surgery and avoid postoperative delirium,” Fleisher said. “While these have not been scientifically proven to help, we think that even the smallest measures may make a difference for patients who are coming out of anesthesia.”

To learn more about delirium and aging, join the Institute on Aging on Tuesday, April 18, 2017 for our Visiting Scholars Series lecture by Edward Marcantonio, MD, SM.

Dr. Marcantonio is the Section Chief for Research in the Division of General Medicine and Primary Care at Beth Israel Deaconess Medical Center and Professor of Medicine at Harvard Medical School. His research concentrations focus on delirium and cognitive function.

For more information, visit: www.med.upenn.edu/aging/events


Photo credit: news.pennmedicine.org/blog

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.

The National Institute on Aging’s Luigi Ferrucci, MD, PhD receives the IOA’s 2016 Joseph A. Pignolo Award in Aging Research

On Thursday, October 27, 2016, the Institute on Aging hosted its 2016 Joseph A. Pignolo Award in Aging Research event. The recipient of this year’s award — which is given annually to recognize significant contributions in the field of aging research — was Luigi Ferrucci, MD, PhD, an epidemiologist and geriatrician who is currently the Scientific Director of the National Institute on Aging (NIA) and Chief of the Longitudinal Studies Section.

During his lecture on “The Mechanisms of Age-related Loss of Muscle Biomechanical Quality,” Dr. Ferrucci discussed his work on trying to uncover the reasons why we lose muscle mass and strength in aging. “The important thing to understand is not why the muscles shrink, but why we lose muscle quality,” he said.

Watch the video below for a summary of Dr. Ferrucci’s lecture:

Dr. Ferrucci also shared a glimpse into other research happening at the NIA, including a relatively new study in which they selected a small population of healthy individuals in hopes of understanding their secret to maintaining their health in old age. They are conducting in-depth analyses of genomes, epigenetics, blood, and other tissue samples including muscle and skin biopsies. Through their research, they hope to develop technologies that do not require such labor-intensive interventions to be measured and can apply them to new generations of epidemiological studies of aging.

Dr. Ferrucci received the 2016 Pignolo Award in Aging Research for his 2015 publication, “Gene expression markers of age-related inflammation in two human cohorts,” in Experimental Gerontology. His research focuses primarily on the causal pathways leading to progressive physical and cognitive decline in older persons, and in particular, inflammation.

This publication was an attempt for Dr. Ferrucci and his colleagues to look at the genetics of aging in a “somewhat nontraditional way,” he said.

To read the full publication, click here.

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