Spring 2015 E-Newsletter

Easton Center Welcomes New Director of Clinical Programs
Photo: Verna R. Porter, M.D., F.A.N.A.

We are delighted to announce that Verna R. Porter, M.D., F.A.N.A. has joined the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA (UCLA-Easton Center) as Director of Clinical Programs on June 1st, 2015. Dr. Porter’s responsibility is not limited to the oversight of the center’s clinical operations, but is also to collaborate closely with colleagues in facilitating access to clinical trials within the program. In addition to her new role at the UCLA-Easton Center.

Dr. Verna Porter has been a Bruin ever since 1986; she received her undergraduate and doctoral degrees, and served her Medicine Internship, Neurology Residency, and Fellowship in Geriatrics and Behavioral Neurology and Neuropsychiatry at UCLA. Dr. Porter comes to us after having been Chief of the Neurology Section at Santa Monica/UCLA Medical Center from 2002-2015. Her commitment to serving patients and their families, as well as the many residents she has trained over the years, is laudable. Dr. Porter’s goal is to keep the UCLA-Easton Center at the forefront of clinical care for patient with Alzheimer’s disease (AD). Her mission is to continue to expand the clinical services of the UCLA Alzheimer’s Disease Research Center (UCLA ADRC), and to provide a dynamic patient experience, focused on delivery of the best possible clinical care to patients with AD and associated neurodegenerative diseases.

Finally, Dr. Porter is looking forward to continuing to develop her clinical research interests in the neuroimmunology and neuroinflammatory pathophysiology of AD. It has been an area that has intrigued Dr. Porter since her fellowship training in the late 90’s in the UCLA Dementia, Behavioral Neuroscience, and Neurogerontology programs. Dr. Porter is also a Fellow in the American Neurological Association (ANA), and holds subspecialty certification (United Council for Neurological Subspecialties) in Behavioral Neurology and Neuropsychiatry in addition to her board certification from the American Board of Psychiatry and Neurology (ABPN).

Please join us in welcoming Dr. Verna Porter to the UCLA-Easton Center!

The John/Bredesen Drug Discovery Lab Gives New Hope in Treatment of Alzheimer's

Photo: JBDDL lab members from Left to right: Jesus Campagna, Varghese John, Ph.D., Barbara Jagodzinska, Ph.D., and Patricia Spilman, M.A.

When Drs. Dale Bredesen, M.D., and Varghese John, Ph.D., came to the Mary S. Easton Center for Alzheimer’s Disease Research at UCLA, they brought with them the John/Bredesen Drug Discovery Lab, and the potential for a new arsenal aimed at the treatment of Alzheimer’s: the MEND program and the drug F03.

At UCLA, the JBDDL’s goal is to identify new targets and compounds for development as Alzheimer’s disease treatments. The team is off to a strong start. While at the Buck Institute for Research on Aging, it identified tropisetron (F03), an established anti-nausea drug, as a potential new treatment for Alzheimer’s disease (AD). The drug works because it increases sAPPα – a peptide that supports brain health. F03 is now in an Australian clinical trial assessing its impact on patients suffering from mild cognitive impairment (MCI), which often precedes AD.

Photo: Dale E. Bredesen, M.D.

MEND is a comprehensive and personalized therapeutic program which involves multiple methods designed to achieve metabolic enhancement to slow or arrest neurodegeneration. "The existing Alzheimer's drugs affect a single target, but the disease is more complex. Imagine having a roof with 36 holes in it, and your drug patched one hole very well," Bredesen said. "The drug may have worked, and a single hole may have been fixed, but there are still 35 other leaks."

The MEND pilot study enrolled ten patients reporting memory loss confirmed by cognitive assessment. Nine had mild cognitive impairment (MCI) and one had moderate to advanced AD. The results of this small study were positive, showing a reversal of memory loss associated with MCI. In this initial pilot study, the MEND program was tailored to the specific signaling network in each patient’s individual case and based on a detailed medical diagnosis including blood, cognitive tests, and brain imaging. The program was then adjusted to meet the needs of each participant. Some components included: dietary adjustments (eliminating simple carbs, gluten and processed food; eating more vegetables, fruits and non-farmed fish); meditation; increased sleep; enhanced vitamin intake; optimized oral hygiene; and exercise.

The study found that MEND had most impact on the MCI patients, where decreases in cognitive ability are slight, but noticeable, to the person him/herself and to those who know them well. In this earlier stage of decline in cognition intervention is more likely to improve brain health and delay or prevent the onset of AD.

Bredesen further cautions that the program is complex, difficult to follow, and does not constitutes current standard of care. The initial study results, though positive, are anecdotal as they were obtained in a very small group of patients. The results need to be confirmed and the protocol refined in further clinical studies. Accordingly, at present, the Easton Center is not accepting any more MEND study participants, but in the future, the Center hopes to further assess and develop MEND in a much larger, controlled clinical trial. In the meantime, Bredesen and the JBDDL continue to develop potential new drug targets in the treatment of AD, and explore whether these drug targets may be used in combination with MEND to further enhance its potential benefits.

Easton NeuroImaging Lab

This past year was especially productive time for the junior members and trainees of the Easton Imaging Laboratory directed by Dr. Liana G. Apostolova.

"Conferences provide a wealth of opportunities and resources for us to network, learn, and gain insight into our work. As a trainee, it is truly a unique experience to not only engage with specialists in the field, but also to step on stage and demonstrate to the crowd all that our research has to offer. The opportunity to interact closely with the research world was a vital component of my path to graduate school, and I am thrilled to begin my PhD training in Clinical Neuropsychology at the University of Southern California this fall. I’m thankful to everyone involved with the Easton Center, and I will continue to share a passion to find a cure for Alzheimer's disease."

"It was truly an honor to represent the Easton Center for Alzheimer’s Disease Research amongst experts. Our success is a testament to the impact that the dedication of our study participants has on Alzheimer's research. Our patient’s efforts are not in vain and we are inching closer to finding cures for Alzheimer's disease and many other incurable neurological diseases."

"It has been rewarding and motivating to attend these conferences and to have fellow researchers and physicians interested in my work. With the experiences gained at the Easton Center and conferences across the nation and the support of Dr. Apostolova and my co-workers at UCLA's Easton center, I will continue contributing to the medical field with novel findings and insights to neurodegenerative diseases."

"Dr. Apostolova's lab had a strong positive influence on my career. I had past research experience studying AD in mice at UC Merced, but working with patient data at UCLA helped me understand the more clinical and personal aspects of the disease. While working at UCLA, I was accepted into the very competitive National Institute of Health (NIH) Undergraduate Scholarship program (UGSP). My time in Dr. Apostolova's lab was also critical in my acceptance into the UC Irvine Interdepartmental Neuroscience Program where I will begin pursuing my PhD in the fall."

Clinical Trials Program
Photos: (left to right) Sarah A. Kremen, M.D. and Edmond Teng, M.D., Ph.D.

The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study:

Almost one year ago, the Kagan Clinical Trials program began participating in a land breaking clinical trial, The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease Study (the “A4 study” for short). Along with 60 other centers across the country, the goal is to enroll 1000 participants who have normal memory and thinking function, but who may be at risk for developing Alzheimer’s disease (AD) in the future. Longitudinal studies of AD have shown that build up of a protein thought to contribute to the development of the disease, called amyloid, occurs up to 20 years before the onset of identifiable symptoms. The overall goal of the A4 study is to test whether an investigational treatment targeted against amyloid can decrease brain amyloid levels and help slow the memory loss associated with amyloid build up in some participants. Unlike previous AD trials, this trial is unique in its focus upon treatment of asymptomatic people, with the hope that this approach may catch the disease early enough to change the course of its development. The A4 Study lasts for three years. Participants will be assigned at random to receive either the investigational drug or a placebo, and will be monitored over that period.

The Kagan team is looking for interested participants for this study. You may be eligible to join the A4 study if you:

• Are 65 to 85 years old
• Have normal thinking and memory abilities
• Have a study partner (someone who has weekly contact with you and is willing to answer questions once a year).

If you are interested in participating, please call (310) 794-6191 or visit www.eastonad.ucla.edu.

Wine Bears New Fruit in the Fight Against Alzheimer's
Photo: David B. Teplow, Ph.D.

An intriguing observation was made some years ago—red wine appears to protect against Alzheimer's disease (AD). A team led by Easton Center researcher Dr. David B. Teplow has worked for a number of years to find out how.

Studies using mice had shown that chemical compounds in the wine apparently could prevent the accumulation of toxic brain deposits of a protein known as the amyloid β-protein (Aβ), pronounced "A-beta." These mouse oenophiles, unlike their water-loving neighbors, showed many fewer Aβ deposits and were better able to remember their way in laboratory mazes.

The chemical compounds thought to be responsible for improved memory are called "polyphenols." These small compounds are plentiful in nature. Sources include berries, tea, beer, olive oil, chocolate/cocoa, coffee, walnuts, peanuts, pomegranates, popcorn, and red wine. Polyphenols are potent anti-oxidants, which makes them desirable nutraceuticals (pharmaceuticals from nature).

Teplow's team studied how these polyphenols could affect the formation of large clumps of Aβ by chemically synthesizing the Aβ protein in the laboratory. They found that adding a mixture of different polyphenols to the synthesized Aβ prevented the protein from forming small clumps of 2-8 Aβ molecules. This initial clumping event leads to the formation of the large rope-like structures found in human AD patients.

The next question addressed was whether different types of polyphenols had different abilities to block this clumping process. Polyphenols come in a variety of different sizes, including single units (monomers), units of two (dimers), and units of eight (oligomers). When each of these three different types of polyphenols was mixed with Aβ, Teplow's group found that the most active form was the single unit.

These results were quite encouraging, because for such compounds to be effective therapeutic agents, they must be able to move from the bloodstream into the brain. The brain has a natural barrier to protect itself from poisonous things, the "blood-brain barrier." Only relatively small molecules are able to move through this barrier. Polyphenol monomers are small enough to do so, and thus should be able to surround nerve cells and prevent their damage by Aβ clumps.

A scientific publication reporting this work to the world currently is in preparation. This is the first step in the long process of moving scientific discoveries "from the bench to the bedside," i.e., translating basic science research into drugs that can be tested in human clinical trials. The Teplow group, working in close collaboration with the Mary S. Easton Center for Alzheimer's Disease Research at UCLA, hopes to do just that. Such work is critical if new treatments are to be developed for the millions suffering from AD in the United States.

Until clinical trials have been completed successfully, should people drink more red wine? Teplow opines, as have others, that moderate consumption of red wine (up to two glasses per day for men and one for women) is enjoyable and safe, but whether such consumption alters AD risk or disease symptoms remains unclear.

New Additions to the Easton Center

As the center expands and we begin new studies, we're fortunate to add new and excellent team members. Please join us in welcoming several new staff members to the Easton Center.

Barbara Dwyer, C.M.A.
Barbara was raised and had her formal schooling here in the Westwood area, went on to pursue higher education at USF and has been growing along with the UCLA Clinical Neurology team since 2012. She joined the Easton Center on April 1, 2015 and is deeply committed to provide personal service to our patients, their families and caregivers. Barbara functions as Patient Coordinator and works closely with clinical program specialists to provide exceptional patient centered care. She is a Certified Medical Assistant and brings with her many years of customer service experience, knowledge of Neurological diseases and familiarity with referral triage, clinic scheduling and UCLA patient registration and communication systems. She has three adult sons and enjoys spending time with them skiing, hiking, cooking and is also fond of watching EPL soccer, UCLA and NFL football and Dodger baseball. Barbara is happy to talk to you anytime, but she is even happier to just listen.

Michelle Mather, M.A.
Michelle has been a Study Coordinator in dementia since 2009 and is now on board with the Kagan Center for clinical trials. She is excited to join the crusade to discover new treatments and to get to know a new group of study participants. She is also a registered intern in Marriage and Family Therapy volunteering at the Southern California Counseling Center. In her spare time, she loves to read nonfiction, bake goodies of any sort, and watch TV shows from the 50s and 60s.

Monica Moore, M.S.G.
Ms. Moore has worked in the field of aging for more than 15 years. She holds a Masters Degree in Gerontology from California State University Long Beach and graduated from Sonoma State University in 1998 with a BA in Human Development and a Certificate in Gerontology. Ms. Moore has extensive experience working with people with Alzheimer's disease, their families, and caregivers. Ms. Moore has worked for the Alzheimer's Association, is currently a member of their volunteer Speakers Bureau, and leads support groups for people with early onset Alzheimer's disease and their caregivers.

Aurora Rosales, M.A.
Aurora Rosales joined the Cognitive Neuropsychology Lab in April 2014 and works with Drs. Christopher Nunez and Ellen Woo. She earned a master's degree in clinical psychology and has 12 years of clinical research experience. Previously, she collaborated with the Easton Center as the study coordinator at Harbor-UCLA Medical Center site in 2011. She currently administers neuropsychological tests to Spanish-speaking bilingual and monolingual participants both at UCLA in Westwood and Olive View - UCLA Medical Center in Sylmar.

Clinical Research Opportunities

If you would like to advance Alzheimer's disease research, please consider participating at the Easton Center. Below are two current trials. For a complete list of enrolling studies, visit our website at www.eastonad.ucla.edu.