| Translational Research | Phase III Trial of an Investigational Drug |
| New Additions to the Easton Center | Caregiver Support Group |
| Clinical Trials | Upcoming Events |
Translational Research that Tests Potential Prevention and Therapeutic Approaches in Animal Models
The Cole and Frautschy laboratories at the Mary S. Easton Center are dedicated to translational research that tests potential preventative and therapeutic approaches in animal models (transgenic flies, mice and rats) that carry versions of human genes that influence Alzheimer's disease (AD) risk, such as APP, MAPT, and APOE. Our goals are to determine how these genes lead to AD, how to block the biochemical pathways that are involved and to find novel blood-based biomarkers for specific features of the disease that can help identify early responses to treatment. Some of our recent work has focused on the effects of the ε4 version of the APOE gene, which is associated with greater risk of AD, on micro-RNA that normally limit the amount of harmful inflammation in the brain. These micro-RNA levels are decreased in individuals who have the APOE ε4 gene. Since micro-RNA levels can be monitored in blood and can be regulated by drugs or diet and exercise, we hope to use it to monitor treatments for mitigating the risk of Alzheimer’s caused by the APOE ε4 gene.
More efficient strategies for identifying more effective interventions to treat or prevent AD are badly needed. Currently, clinical trials for AD typically take years to complete and require the participation of up to a few thousand patients per study. While they primarily focus on endpoints that are important to patients and families, such as cognition and function, these outcomes can be difficult to measure precisely, which contributes to the high costs and long studies needed to evaluate potential treatments. These hurdles limit the number of candidate drugs that can be tested.
Therefore, other research in our laboratories is aimed at detecting beneficial drug effects in blood tests that may emerge more rapidly their effects on cognitive testing. "Nanoparticles" are detectable in the blood and carry both messages and "debris" from different organs in the body, including the brain. These nanoparticles (also called exosomes and ectosomes) are coated with different molecular markers that can be used identify what kind of cells that they originate from. In AD, these particles contain the aggregates of the Aβ and tau proteins that are thought to cause the disease, as well as evidence from affected brain cells that indicate how they have been damaged (for example, their inability to respond to insulin). Such biomarkers will allow us to more precisely and efficiently monitor the progression of AD in individual patients and how they respond to different interventions.
We are beginning to learn about this new window on the brain by working with researchers across the Easton Center and at other UC campuses and purifying and analyzing such particles from blood and brain samples. Our group has produced evidence that brain-derived nanoparticles are influenced by the APOE gene and Aβ accumulation and are quickly removed from human blood in minutes. Therefore, they should provide real-time updates about what is currently happening in the brain, including rapid responses to candidate protective drugs. Such tools have potential to identify whether potential new drugs are working within weeks or months, rather than the 1-2 years that current clinical trials require, and thus move us far more quickly and efficiently towards more successful therapeutics. To this end, we are currently analyzing blood samples from Dr. Liana Apostolova's Imagene study of cognitively normal individuals and early stage AD patients who have been carefully followed for 4 years using amyloid and brain imaging methods, gene expression profiling, and tests of learning and memory. While those trial participants are untreated, we are looking for treatment responses in blood samples from our clinical trial in early stage AD patients (see below).
We are also testing earlier stage novel therapeutics in animal models including mice and rats that carry the APOE ε4 allele, Aβ plaques, and/or tau tangles that exhibit increasing AD pathology, neuron loss, and memory deficits with increasing age. Some of the drugs and dietary supplements the we are investigating target the damage caused by amyloid and tau, while others, developed by Dr. David Eisenberg, another member of the Easton Center, target the abnormal aggregation of tau seen in AD. These protein aggregation inhibitors have shown protective effects in multiple models.
Our animal studies have also explored combination "multi-domain" interventions such as diet and exercise, and some of our successes in the laboratory are now being tested in human clinical trials. For example in collaboration with Dr. Edmond Teng, one of the Co-Directors of the Easton Center's clinical trial group, we are conducting a clinical trial to determine if the combination of the turmeric root molecule curcumin with yoga can prevent individuals with mild cognitive impairment from progressing to AD dementia. Curcumin targets AD through multiple pathways, as it binds to toxic Aβ and tau aggregates, helps clear them out of the brain, and corrects aberrant inflammation. Exercise may be complementary, as it can promote the generation of new brain cells. We hope that these interventions have the potential to restore memory or halt progression in patients at initial stages or even with full-blown AD pathology and/or at later stages of disease.
ENGAGE: A Phase III Trial of Aducanumab
Amyloid PET scan in a participant at baseline (left) and after one year on aducanumab treatment (right) shows decreased amyloid after treatment. [Image courtesy of Biogen.]By: Sarah Kremen, M.D.
The Katherine and Benjamin Kagan Alzheimer’s Disease Treatment Development Program continues to participate in multicenter clinical trials that focus on developing new therapeutic interventions in earlier stages of Alzheimer’s disease. Our newest exciting trial for which we are recruiting participants is the ENGAGE study, which is examining the effects of the experimental drug aducanumab in patients with mild cognitive impairment due to Alzheimer’s disease. The study is sponsored by Biogen and is being conducted at 150 centers in North America, Europe, Australia, and Asia.
Aducanumab is a drug that binds to β-amyloid deposits in the brain and clears them, reducing the brain amyloid level. Beta amyloid is a hallmark protein of Alzheimer’s disease and is believed to be a trigger for neuron loss, inflammation, and cognitive and functional decline associated with the disease.
Aducanumab is an infusion, delivered to the bloodstream by IV into the arm. In a prior Phase Ib study of 165 people with mild cognitive impairment or mild dementia due to Alzheimer's disease, in which UCLA was a participating site, aducanumab significantly reduced the amount of β-amyloid in the brain relative to placebo infusions. The data from this small study suggested that aducanumab may slow cognitive and functional decline in early stages of Alzheimer’s disease and the recently published results made headlines. This medication was well tolerated by most participants.
The current study is a Phase III trial with the intent to enroll 1350 participants at sites around the world. The primary goal of this study is to determine whether aducanumab can slow down the progression of cognitive and functional decline in people with mild cognitive impairment from Alzheimer's disease.
You may be eligible to join ENGAGE if you:
Potential study participants will undergo brain imaging with both MRI scans (which provide information about the structure of the brain) and amyloid PET scans (which provide information about how much amyloid protein is in the brain). Only individuals who have elevated brain amyloid levels will be enrolled in the study. Those individuals will receive monthly infusions of either aducanumab or placebo (i.e. inactive substance) for an 18-month period. Participants will also undergo periodic cognitive testing and MRI scans.
New Additions to the Easton Center
Please join us in welcoming two new members to the Easton Center's Neuropsychology Program.
Photo: Fini Chang
Fini graduated with a B.S. in Psychobiology from UCLA in 2015. She has been a research assistant in various labs, ranging from studies on sleep and mood disorders to conditioning in anxiety disorders. She is now exploring the field of neuropsychology in Alzheimer's disease as she joins the Easton Center. Ultimately, she plans to pursue a Ph.D. degree in clinical psychology. We welcome Fini as a Staff Research Associate in the Cognitive Neuropsychology Lab at the Easton Center!
Photo: Carlee Kreisel
Carlee is a Los Angeles county native and graduated from Loyola Marymount University in December with a bachelor’s degree in Psychology. She was heavily involved in research at her undergraduate institution, and she examined the effects of caffeine on mental workload. She has presented posters and given talks at multiple research conferences, and plans to enroll in a Ph.D. program in clinical psychology. She is very excited to be a part of UCLA. We welcome Carlee as a Staff Research Associate in the Cognitive Neuropsychology Lab at the Easton Center!
Support Groups: Support for Your Caregiving Journey
Caring for a person with Alzheimer's disease or another form of dementia is no doubt a difficult job that millions of caregivers take on. Not only does the caregiver have to attend to the daily personal and emotional needs of the person for whom they are caring, they also have to tend to their own needs and responsibilities of life, which might include working and raising a family. Caregiver burn out occurs to caregivers of people with Alzheimer's disease sooner than for caregivers of people with other illnesses. Finding a way to avoid burnout is crucial to the life and success of the caregiver. Support groups provide a safe place to talk, cry, yell, and to be listened to by people who understand. Support groups remind caregivers that they are not alone, and they can be a helpful place that can make your life easier, reduce stress, and improve your health.
According to the Alzheimer's Association, nearly 60 percent of Alzheimer's and dementia caregivers rate the emotional stress of caregiving as high or very high; about 40 percent suffer from depression. One in five caregivers cut back on their own doctor visits because of their care responsibilities. And, among caregivers, 74 percent report they are "somewhat" to "very" concerned about maintaining their own health since becoming a caregiver. Finding an outlet for the emotions and struggles of caregiving is crucial. Support groups can be in person, on the phone, on line, during the day and/ or during the night to accommodate the working caregiver. No two groups are alike as it is the members and their journeys and stories that make the groups unique.
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.
Study of A Beta Secretase Inhibitor in Prodromal Alzheimer's Disease:
The Easton Center is currently participating in a Phase III clinical trial sponsored by Merck & Co of the investigational drug MK-8931. MK-8931 reduces levels of the beta amyloid protein by inhibiting the activity of an enzyme called beta secretase. MK-8931 is an oral medication taken daily. The study is approximately two years long, with roughly 12 study visits. Participants will be randomly assigned to the active study medication (MK-8931) or placebo. A placebo is a pill that looks just like the active medication but has no biological activity. Individuals age 50-85 who have a memory problem are potentially eligible for this study. If you are interested in participating, please call (310) 794-6191 or visit www.eastonad.ucla.edu.
FYN Kinase (CONNECT) Study:
The CONNECT study will test whether an oral, experimental drug, AZD0530 (saracatinib), will slow progression in mild-stage Alzheimer’s disease (AD). Although the cause of AD is unknown, several lines of evidence suggest that a peptide known as beta-amyloid plays a central role. Convergent evidence in recent years has yielded a refinement of the "amyloid hypothesis", suggesting that neurotoxicity of beta-amyloid oligomers leads to Alzheimer's disease. The protein Fyn kinase, a member of the Src family kinases, may play a fundamental role in the pathway by which beta-amyloid oligomers damage neurons. AZD0530 is a selective inhibitor of Src family kinases that was previously developed as a cancer therapy but may hold greater promise as a treatment for AD. Researchers will use PET imaging to evaluate whether the drug is effective in slowing decline in brain metabolism and will also determine whether it is safe and well tolerated in patients with AD. Screening will occur over six weeks followed by a 52-week treatment period. The study requires a minimum of four visits during the screening and 13 to 14 visits during the course of the treatment. 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:
2016 Alzheimer’s Association | Walk to End Alzheimer'sTM in Santa Monica, CA
Date: Sunday, October 9th, 2016
Time: 8:00 a.m. - 12:00 p.m.
Location: Santa Monica, CA
Held annually in more than 600 communities nationwide, the Alzheimer's Association Walk to End Alzheimer’s® is the world's largest event to raise awareness and funds for Alzheimer’s care, support and research. This inspiring event calls on participants of all ages and abilities to reclaim the future for millions!.
The Alzheimer's Association is the leading voluntary health organization in Alzheimer's care, support and research. Join the UCLA Easton Center Team for Walk to End Alzheimer's®.
2016 Walk 4ALZ | Alzheimer's Greater Los Angeles in Century City, CA
Date: Sunday, November 6th, 2016
Time: 7:00 a.m. - 12:00 p.m.
Location: Century Park, Century City, CA
Walk4ALZ brings together local communities in the fight against Alzheimer’s and other dementias. Whether you are living with dementia, caring for someone with dementia, lost someone to Alzheimer’s disease, or simply want to make a difference in our community, join the UCLA Easton Center Team for Walk4ALZ.
Alzheimer's Greater LA is a local organization whose mission is to provide Greater Los Angeles families with hands-on support, information and resources, while advancing critical local research for a cure.
New support groups are being planned! In addition to the joint Easton Center and the UCLA Alzheimer's and Dementia Care Program, which focuses on caregivers of patients with Alzheimer's disease, soon we will be offering additional support groups for caregivers of patients with Dementia with Lewy Bodies, Early Onset Alzheimer's Disease, and Frontotemporal Dementia. Details to come soon!