Retinal Amyloid Imaging in Aging Israeli Populations At High Risk for Alzheimer’s Disease
Collaboration between Scientists at Sheba Medical Center, Israel and Cedars-Sinai Medical Center, LA to assess a novel amyloid imaging technology
THE PROBLEM Millions of people are affected by the growing epidemic of Alzheimer’s disease (AD), an invariably fatal, degenerative disease of the brain. It is the leading cause of dementia, and ties with stroke in developed countries as the third leading cause of death among the elderly. The probability of getting AD increases from 10% at age 65 to over 50% at age 85. Within the rapidly aging population, the number of people affected by AD (currently over 44 million worldwide) is expected to more than double by 2040. The cost of care for those with AD in the US alone is estimated to be well over $200 billion per year.
Early and unequivocal diagnosis of AD is critical for identifying populations that can benefit from early prevention or therapeutic interventions. However, there is no method available for detecting and treating AD that is both reliable and practical. Definitive AD is confirmed only after death, at brain autopsy. Cognitive tests such as the Mini Mental State Examination can determine level of impairment, but not the underlying biology. Elevated amyloid-beta, the hallmark brain marker of AD, has been shown to be a very early and specific event in AD. It is believed to begin 10-20 years prior to symptomatic cognitive decline. Progress has been made towards imaging anatomical changes and amyloid accumulation directly within the skull-shielded brain using techniques such as MRI and PET. Still, there are many difficulties and limitations inherent to these techniques, including low specificity, poor spatial resolution, high costs, inaccessibility and radioactivity.
THE SOLUTION In order to prevent AD, one of the major problems facing our modern world, and the aging population in particular, we are proposing to join forces between Israeli scientists based at Sheba Medical Center in Israel and Cedars-Sinai Medical Center in Los Angeles, CA. Dr. Maya Koronyo’s team at Cedars-Sinai has invented and clinically validated a one-of-a-kind retinal amyloid-beta imaging technology, a non-invasive tool for potential detection of the earliest pathological signs of AD in the eye, reflecting the pathology in the brain. The availability of a tool that can detect pathology and monitor responses to AD therapies would greatly benefit the aged population, who is at high risk for developing AD dementia.
Large-scale studies within Sheba Medical Center involve exquisitely well-characterized patients who do not yet have AD, but are at high risk for the disease due to a family history of AD or to diabetes. We aim at employing this novel retinal amyloid technology, within Israeli studies led by Dr. Michal Beeri, the Director of the Joseph Sagol Neuroscience Center at Sheba, Israel. Importantly, the retinal amyloid technology has been clinically validated and correlated with brain-amyloid imaging in 200 patients. Its massive potential for very early detection of AD and for response to therapies has made an impact on both the AD research community and on the general public including prime time news and articles in Forbes, The Wall Street Journal, and more.
DRS. BEERI AND KORONYO, TOGETHER, ARE LEADERS IN THE RACE FOR EARLY DETECTION AND TREATMENT FOR ALZHEIMER’S DISEASE: The novel retinal amyloid technology will be applied in two large-scale long-term projects. The Israel Diabetes and Cognitive Decline study, is comprised of diabetics who are at high risk for developing AD. The Israel Registry for Alzheimer’s Prevention, examines offspring of AD patients who are thus at high risk of developing AD. Both projects follow initially non-demented participants, and characterize in detail their cognitive, medical, lifestyle, brain imaging, and biological profiles (vascular function, bloods, genetics, and cerebrospinal fluid) over time. Recently, Dr. Beeri brought to Israel brain amyloid imaging to be used in live people. This will provide an invaluable opportunity to study amyloid deposits in the retina and the brain, further characterizing the profile for those at the very initial stages of AD. Exquisitely detailed medical history dating back 20 years from the Israeli HMOs is streaming into both studies, providing an unequaled advantage compared to any other place in the world. Noninvasive retinal scan technology will allow for frequent monitoring of the amyloid buildup in these patients. Consequently, distinguishing profiles of individuals at low versus high risk for developing AD will assist with earlier and more effective prevention and treatment. Linking retinal amyloid-beta burden to other markers of AD (lifestyle, emotional, etc.) will permit unique discoveries of the profile of markers that predict AD long before the clinical symptoms manifest, the most effective window of opportunity for curing AD.
|Sheba’s budget||Cedars’s budget|
|Equipment (ophtalmoscope)||$150K||Training of Israeli team by Cedar’s experts||$20K|
|Retinal amyloid imaging of 120 patients (50 diabetics, 50 with AD family history, 20 controls). $416 per image.||$50K||Personnel (study design, technical support, image analyses, quantification of retinal amyloid, interpretation, report of results, etc.).||$80K|
|Personnel (patient recruitment, informed consent, training participants for curcumin use, obtaining retinal amyloid images, transfer of images, etc.)||$150K||Retinal and Brain tissue study of Alzheimer’s pathology. Immunological Blood biomarkers.
Travel to Israel
|Overall total: $500K|
MILESTONES AND TIMELINES We are seeking $500K to support the establishment of the first retinal-amyloid imaging testing center in Israel, which we anticipate will take 18 months. Following purchase of the relevant equipment, Dr. Koronyo’s team will come to Israel to train the Sheba team on all aspects of retinal amyloid imaging. The Sheba team will perform proof of concept studies based on the participants with high AD risk described above. These studies will give the critical scientific and feasibility basis for developing definitive evidence for the validity and usability of retinal amyloid as a sensitive tool for early diagnosis of AD and for response to novel treatments. Ultimately, our goal is implementing this exciting technology in the community.
Dr. Maya Koronyo, Assistant Professor, Neurosurgery and Biomedical Sciences, Principal Investigator, Maxine Dunitz Neurosurgical Institute
Dr. Koronyo has investigates neurological disorders for over 15 years. She received her BSc (Cum Laude) from Tel-Aviv University, then obtained an MSc (Summa Cum Laude) and a PhD with excellence in Human Molecular Genetics (neurological disorders) from The Sackler School of Medicine (Tel-Aviv University) and Sheba Medical Center. She pursued a post-doctoral fellowship in a worlds’ leading neuroimmunology laboratory at the Weizmann Institute of Science, Rehovot. She was recruited by Dr. Keith L. Black, Chair of the Cedars-Sinai Neurosurgery Department, to build a neuroscience laboratory from the ground up. Dr. Koronyo’s lab is highly engaged in developing powerful immune-based strategies to prevent and cure AD. Her Team has identified for the first time amyloid-beta deposits in the retina of AD patients and pioneered the technology for noninvasive imaging of retinal amyloid-beta plaques in living subjects. Dr. Koronyo’s groundbreaking discoveries have been featured in several seminal peer-reviewed publications in the highest impact medical journals. Her lab has been funded by the US National Institutes of Health (NIH), The BrightFocus Foundation, and more. Dr. Koronyo received the Pioneer in Medicine Award from the World Brain Mapping Foundation, and the prestigious National Institute on Aging Award for the Retinal Amyloid Imaging innovative technology.
Prof. Michal Beeri, Director, Sagol Neuroscience Research Center, Sheba Medical Center; Associate Professor, Department of Psychiatry, Mount Sinai School of Medicine
An Israeli leader in the study of AD, she is the Director of the Joseph Sagol Neuroscience Center at Sheba. She is also a board member of the Israel Brain Technology Foundation, initiated by former president Shimon Peres. Trained in business and psychology (Summa Cum Laude), Prof. Beeri received her PhD in psychology from Bar Ilan University in Israel (2000). Prof. Beeri’s primary academic affiliation is at the Icahn School of Medicine at Mount Sinai, NYC (since 2001). She also holds several senior academic affiliations in Israel. Michal won numerous professional awards; she has over 100 peer-reviewed publications and has been funded continuously by the US NIH, Alzheimer’s Association, BrightFocus and other prestigious foundations since 2003. Her career has been fully devoted to the study of cognitive impairment and AD. Her primary focus is on the identification of risk and protective factors of AD that can be manipulated early in the course in order to prevent the disease.
Dedication and Naming Opportunities:
- Sheba Medical Center & Cedars Sinai Medical Center Collaboration $500K per year
- Pediatric Neurosciences Center, $25 million
- Alzheimer’s Center, $15 million
- Adult Neurosciences Center, $10 million
- Metabolic, Endocrine and Diabetes Center, research wing, $1 million Completed!
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