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2016 Turken Research Award Symposium
Photo: (Left to right) Dr. Debra Cherry, Dr. Gregory Cole, Dr. Lin Jiang, Ms. Beth Devermont, and Ms. Susan Galeas.
By: Greg Cole, Ph.D.
Like healthy evergreens, the neurons that we think and remember with are constantly replenishing their arbor, growing close to each other and connecting to create a forest of memories. As Alzheimer's disease develops and produces neurotoxic protein aggregates, these neurons stop making new connections and begin to die back and stand-alone. Like dying trees, many still show signs of life, but we don’t yet know how to rescue them. Researchers at the Easton Center are finding new and better ways to prevent or block the toxic aggregates that give rise to Alzheimer's disease.
Some of the groundbreaking work that these researchers have been engaged in was presented at this year's Turken Research Award Symposium, which took place on October 14th. This annual symposium is sponsored by the Sam and Ida Turken Charitable Foundation, which has been supporting Alzheimer’s disease research, particularly by early-career investigators, since the early 1980's. Ms. Beth Devermont, President and Director of the foundation, has continued her mother's legacy in association with Alzheimer's Greater Los Angeles. The Turken Research Award Symposium honors her continuing contributions by providing a forum to discuss the latest Alzheimer's disease research at UCLA and to present the annual Turken Research Award this year's recipient, Dr. Lin Jiang.
Dr. Jiang's research program centers on preventing the neurodegeneration caused by protein aggregates. His work has been stimulated by prior studies that indicate that when specific neurotoxic proteins accumulate in the brain, they can lead to the development of different diseases. For example, Alzheimer’s disease features aggregates of beta amyloid and tau proteins, Parkinson’s disease results from aggregation of alpha-synuclein protein, and amyotrophic lateral sclerosis can be caused by aggregation of TDP-43 protein. The inhibition of toxic aggregates has become a major goal for drug companies and researchers trying to treat or prevent Alzheimer's disease and related disorders. Collectively, millions of chemicals in "drug libraries" have been laboriously tested for their ability to block aggregates of amyloid and tau. Unfortunately, all of these "high-throughput" drug screening efforts have as yet failed to produce safe and effective drugs. One major stumbling block has been that many of compounds that prevent amyloid aggregation end up having other "off-target" toxic side effects that prevent their use in humans.
Dr. Jiang has taken a different approach. His work focuses on developing precision maps of how such proteins bind to each other on an atomic level to form neurotoxic aggregates. Guided by this knowledge, Dr. Jiang then uses computer programs to design custom inhibitor molecules that precisely interfere with the contact points that allow these proteins to stick to each other. Since these inhibitors are custom designed, they are less likely to interfere with other normal proteins in the body and the brain. To make an analogy, it is like making a "silver bullet" or smart bomb that targets only the terrorists it is intended for and can’t harm the innocent civilians they hide amongst and behind.
Using this approach Dr. Jiang and his mentor, Dr. David Eisenberg, have been making highly specific inhibitors for both amyloid and tau aggregates. The tau aggregation inhibitors are particularly exciting because they have the potential to stop the progression of Alzheimer’s disease. Furthermore, Dr. Jiang has recently identified drugs that have already been approved by the FDA for other conditions that can also block tau aggregation in his cell culture test system. One of the priorities of the Easton Center is to identify funding that would allow us to test these compounds in animals and rapidly transition these findings into the clinic.
Dr. Sally Frautschy presented the findings of her work with Drs. Shuxin Hu, Gregory Cole, David Eisenberg, and Lin Jiang that has investigated the efficacy of a potential tau aggregation inhibitor in both fruit flies and mice that produce human tau protein. This new custom-designed peptide successfully reduced tau aggregates and protected brain cells in these animal models of neurodegenerative disease. While the initial tests in mice involved direct infusion of this compound into the central nervous system as a proof-of-concept, they now plan to test the next generation of tau aggregation inhibitors that can be delivered in a more conventional fashion, which could be more safely used in humans.
Jesus Campagna discussed a project from the Drug Discovery and Translation Laboratory led by Drs. Varghese John and Dale Bredesen. Jesus focused on efforts to derive novel drugs from a compound called AO3 (approved for use in patients in Australia) that helps prevent neurodegeneration in cells that express ApoE4, the major genetic risk factor for Alzheimer's disease. They are performing initial tests to see if AO3 can protect brain cells in genetically modified mice that produce ApoE4. They also started an initial clinical trial in Australia to see if AO3 works in human patients with prodromal Alzheimer’s disease, and are working with UCLA collaborators to find derivatives of AO3 that might work even better than AO3 itself.
The Dean of the UCLA School of Medicine, Dr. Kelsey Martin, who is an internationally renowned expert on the molecular basis of new memory formation, provided the keynote address for the symposium. She discussed her recent elegant studies that indicate that a protein called CRTC1 is required for memory formation in the brain. The production of this protein is disrupted by amyloid at early stages of Alzheimer’s disease, providing a clear link between Dr. Martin’s research and the molecular events leading to this disorder.
Last year’s recipient of the Turken Research Award, Dr. Florence Roussotte, closed the symposium with a fascinating talk suggesting that mood symptoms in aging and dementia may reflect underlying amyloid and tau deposits in the brain. Her work with Drs. Helen Lavretsky, Gary Small, and Jorge Barrio explores the relationships between amyloid and tau levels in the brain (visualized with FDDNP PET imaging) and levels of anxiety and depression. Dr. Roussotte found more amyloid and tau in the brains of older individuals with normal memory and thinking skills but higher anxiety and depression scores. Her results support the idea that anxiety and depression may be byproducts of the early stages of Alzheimer’s disease and lay the groundwork for future PET imaging studies that will examine the impact of anti-depressant and anti-anxiety medications on amyloid and tau levels in otherwise healthy patients.
Overall, the Turken Research Award Symposium re-affirmed the ability of UCLA researchers to stay on the cutting edge of discovery in the fight to prevent or treat Alzheimer’s disease. If you would like to learn more about supporting our research programs, please contact Pamela Thompson at (310) 267-1837.
Helpful Hints for the Holidays
By: Monica Moore
Holidays can be meaningful, enriching times for both the person with Alzheimer’s disease and his or her family. Maintaining or adapting family rituals and traditions helps all family members feel a sense of belonging and family identity. For a person with Alzheimer’s, this link with a familiar past is reassuring.
The tips below can help you and the person with Alzheimer’s make the most out of the holiday season and to find joy in this season.
We hope that these suggestions help you create the time and the space to do the things that bring you joy during the holiday season. The faculty and staff of the Easton Center wish you and yours a happy holiday season and a happy 2017!
Clinical Research Opportunities
If you would like to advance Alzheimer's disease research, please consider participating at the Easton Center. Below are the current recruiting trials. For a complete list of enrolling studies, visit our website at www.eastonad.ucla.edu.
The ENGAGE study is a Phase III clinical trial sponsored by Biogen of the investigational drug aducadumab. Individuals aged 50-85 who are diagnosed with mild cognitive impairment may be eligible to participate in this trial. The goal of the study is to assess whether aducanumab, a drug that targets brain amyloid, can reduce brain amyloid levels and slow memory loss associated with amyloid build up. Participants will be randomized to receive active drug or placebo (inactive substance) via monthly infusions. The study lasts approximately 2 years, which includes an 8-week screening period and 4.5 month follow up period once the investigational drug/placebo phase is completed. To learn more, please call (310) 794-6191 or visit www.eastonad.ucla.edu.
The Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Study:
The Anti-Amyloid Treatment in Asymptomatic Alzheimer’s Disease (A4) Study is a clinical study for older individuals ages 65-85 who have normal thinking and memory function but who may be at risk for developing Alzheimer's disease (AD) memory loss sometime in the future. This study is sponsored by the National Institute on Aging, Eli Lilly, and the Alzheimer's Therapeutic Research Institute. The purpose of the A4 study is to test whether a new investigational treatment can slow the memory loss associated with Alzheimer's disease by decreasing amyloid levels in the brain. The A4 Study lasts for three years, and participants will be assigned at random to receive either the investigational drug or a placebo (inactive substance) via monthly infusions and will be regularly monitored over that period.
You may be eligible to join the A4 Study if you:
If you are interested in participating, please call (310) 794-6191 or visit www.eastonad.ucla.edu.
The CREAD Study: A Study of Crenezumab Versus Placebo to Evaluate the Efficacy and Safety in Participants with Prodromal to Mild Alzheimer’s Disease (AD)
The CREAD study is a Phase III clinical trial sponsored by Genentech/F. Hoffman-La Roche of the investigational drug, crenezumab, which is an anti-amyloid antibody. The goal of the study is to test whether monthly infusions of crenezumab, will slow down disease progression and memory loss by reducing brain amyloid levels. Participants will have a 50% chance of receiving active study drug versus placebo (an inactive substance). The study lasts approximately 2 years, with 26 infusion visits and the possibility of an open label extension upon completion. Individuals ages 50-85 with a diagnosis of mild cognitive impairment (prodromal Alzheimer’s disease) and mild dementia due to Alzheimer’s disease may be eligible to participate. To learn more, please call (310) 794-6191 or visit www.eastonad.ucla.edu.
Curcumin and Yoga Therapy for Those at Risk for Alzheimer's Disease:
Easton Center/UCLA Alzheimer’s and Dementia Care Program Caregiver Support Group
The support group is a collaborative effort between the Easton Center and the UCLA Alzheimer's and Dementia Care Program. It is FREE for family caregivers seeking a supportive environment in which to give and receive emotional and practical support from others who are on the same journey of caring for someone with dementia. For more information or to join the group, please contact Monica Moore at (310) 794-3914.
Frontotemporal Dementia (FTD) Telephone Support Group
This support group is a collaborative effort between the Easton Center and the UCLA Alzheimer's and Dementia Care Program. This FREE telephone support group is designed specifically for family caregivers of those diagnosed with frontotemporal dementia (FTD). Caregivers can share, learn, and gain emotional support from others who are on a similar journey. Please contact Monica Moore for more information and to receive the access code for the call at (310) 794-3914.
Lewy Body Dementia (LBD) Caregiver Support Group
Lewy body dementia (LBD) is a type of progressive dementia that leads to a decline in thinking, reasoning and independent function. The support group is a collaborative effort between the Easton Center and the UCLA Alzheimer's and Dementia Care Program. It is FREE for family caregivers seeking a supportive environment in which to give and receive emotional and practical support from others who are on the same journey of caring for someone with Lewy body dementia. For more information or to join the group, please contact Monica Moore at (310) 794-3914.
Alzheimer's Disease Awareness Day
5.4 million Americans are living with Alzheimer’s disease, including an estimated 200,000 under the age of 65. You are not alone.
Plus! Drop by our Mini Resource Fair to learn more and get your questions answered!
For more information, please call Monica Moore at (310) 794-3914. [Flyer]