An estimated 135 million people around the world will have dementia by 2050, according to a new report by Alzheimer’s Disease International (ADI) released on the eve of the first-ever G8 Dementia Summit in London on December 11th, with the number of victims expected to almost double every 20 years as populations undergo rapid and nearly universal aging. British Prime Minister David Cameron has called on G8 leaders to make dementia a global priority and find research solutions to reduce its increasing impact.
The current economic cost of dementia is $604 billion annually (2010), according to the report, and these costs are expected to escalate at least proportionally with numbers affected, particularly in low and middle income countries.
At the London summit, health ministers from G8 countries discussed ways to tackle the mind-robbing condition. Addressing summit attendees, Dr. Margaret Chan, Director-General of the World Health Organization observed that: “Dementia is a costly and heart-breaking epidemic with an immense impact, medically, psychologically, emotionally, and financially. I can think of no other condition that has such a profound effect on loss of function, loss of independence, and the need for care. I can think of no other condition that places such a heavy burden on society, families, communities, and economies. I can think of no other condition where innovation, including breakthrough discoveries, is so badly needed…. In terms of a cure or even a treatment that is going to modify the disease, we are empty-handed.”
One scientist who has devoted his career to finding an effective treatment for Alzheimers Disease is Dr. Roger N. Rosenberg, M.D., a Professor of Neurology and Neurotherapeutics and Physiology and current holder of the Abe (Brunky), Morris and William Zale Distinguished Chair in Neurology at the University of Texas Southwestern Medical Center in Dallas. Development of a DNA vaccine to prevent neurodegenerative diseases, and Alzheimer’s Disease in particular, has been Dr. Rosenberg’s major scientific interest and the central focus of his laboratory for the past 10 years. He is the founding Director of the NIH-funded Alzheimer’s Disease Center at UT Southwestern, which has gone through five consecutive competitive funding cycles since 1988 and will be funded through 2016 — representing 28 years of continuous NIH Center funding.
Dr. Roger Rosenberg’s Research Into Finding An Alzheimer’s Cure
Dr. Rosenberg’s early amyloid-related research in the UT Southwestern Alzheimer’s Disease Center was directed at determining amyloid precursor protein (APP) processing by neural cells in culture as a model system for the abnormal deposition of amyloid in the brain of Alzheimers disease patients. He described a platelet APP biomarker that correlates with the presence of Alzheimer’s disease. In 2006, he published with Dr. Fred Baskin findings that human platelets utilize beta and gamma secretase to produce amyloid beta 42 and that platelets from Alzheimers disease patients synthesize more amyloid beta 42 than control platelets due to an increased activity of beta-secretase. Platelet amyloid beta 42 levels may be an important bio-marker for Alzheimers disease and a means to monitor effectiveness of drug effect in clinical trials.
A 2011 paper published in the journal Cellular and Molecular Biology (August 2011, Volume 31, Issue 6, pp 867-874), of which Dr. Rosenberg was a senior co-author, notes that the pathogenesis of Alzheimer’s disease (AD) has been strongly associated with the accumulation of amyloid beta 42 peptides (protein) in brain, and immunotherapy targeting amyloid beta 42 provides potential for AD prevention. An earlier clinical trial in which AD patients were immunized with amyloid beta 42 peptide (protein) was stopped when 6% of participants showed meningoencephalitis, apparently due to an inflammatory Th1 immune response.
The paper published by Dr. Rosenberg and his colleagues in 2011, “DNA Immunization Against Amyloid beta 42 has High Potential as Safe Therapy for Alzheimer’s Disease as it Diminishes Antigen-Specific Th1 and Th17 Cell Proliferation” concludes that DNA amyloid beta 42 trimer immunization, as distinct from amyloid beta 42 peptide (protein) immunization, has a high probability to be effective and safe to treat patients with early AD. Immunization with the DNA amyloid beta42 vaccine into the skin with the gene gun produces an immune response that is non-inflammatory in type and results in levels of anti-amyloid Abeta42 antibodies that have the potential to delay or prevent Alzheimer’s disease.
A clinical trial with Alzheimer’s disease patients is a projected objective using this new DNA vaccination methodology, and Dr. Rosenberg in 2009 received a US Patent as the lead inventor of “Amyloid Beta Gene Vaccines”.
Dr. Rosenberg Talks About An Alzheimer’s Vaccine
This week, in an email interview with BioNews Texas president Chris Comish, Dr. Rosenberg expanded on his Alzheimer’s Disease research, his clinical practice, and how he came to UT Southwestern.
BNTX: Can you give us an overview of your educational training and why you chose to pursue a career in neurology and the neurosciences?
RR: College: Tufts University, Medford Mass. Major in Bio-Chemistry; MD Degree with Distinction at Northwestern University Medical School; Chicago, Illinois(1964); Intern in Medicine, Harvard Medical Service, Beth Israel Deaconess Hospital, Boston; Resident and Chief Resident in Neurology, Neurological Institute, Columbia University Medical Center, New York, New York; Research Associate, Laboratory of Biochemical Genetics, National Institutes of Health, Bethesda, Md, Lab. Chief, Nobel Laureate Marshall Nirenberg, PhD.
I have been driven by the question: How does the brain work? I have had an interest in clinical neurology also since boyhood, as my Mother had Raynauds disease — a neurological disorder — and saw how she suffered with it. My family physician was a polio expert in Milwaukee during the epidemics of the 1940s and taught me a good deal about this serious neurological infection causing paralysis. H. Houston Merrit, M.D. and Lewis Rowland M.D. at Columbia sparked my interest in genetic neurological diseases and led to my formal training in molecular genetics in the laboratory of Marshall Nirenberg,PhD. I was a Research Associate in his lab in 1968 when he won the Nobel Prize for the Genetic Code. The combination of clinical and basic neurogenetics was sustained and developed and subsequently, I became interested in the genetics of Alzheimer’s disease.
BNTX: Please share with BioNews Texas the story of how you arrived at UTSW.
RR: I was recruited to become Chairman of the Department of Neurology at UT Southwestern in 1973 by then President of UT Southwestern, Charles C. Sprague, MD. I developed a large clinical and basic science program in neurology, started clinical services at our teaching hospitals, a neurology residency and clerkship for students and recruited a large faculty to teach, care for patients and do research. I developed a laboratory program in Alzheimer’s disease including the DNA vaccine. I obtained as Principal Investigator a NIH Alzheimer’s Disease Center grant in 1988 and have had it renewed five times and it represents 26 years of continuous NIH funding for Alzheimer’s disease research at UT Southwestern representing about $40 million in NIH grant support (1988-2016).
BNTX: How did your research at UTSW ultimately lead to your work with the DNA A 42 vaccine?
RR: I realized that immunotherapy to prevent AD could work if the immune response could be biased to produce an effective level of anti-amyloid antibody and an immune response that was safe and non-inflammatory by injecting DNA for amyloid into the skin of transgenic Alzheimer’s disease model mice carrying the genes that cause human Alzheimer’s disease. The injection was carried out using a gene gun. This methodology did result in a Th2, IgG1 immune response which produced high levels of anti-amyloid antibody that is safe and non-inflammatory. It has potential to prevent AD in at risk asymptomatic persons.
BNTX: Can you provide a brief overview of the vaccine and its promise?
RR: The vaccine is a DNA construct containing segments corresponding to part of the amyloid protein. It produces anti-amyloid antibodies which in our Alzheimer mouse model reduced by 50% the levels of brain amyloid containing plaques and the antibody was shown to be Th2, IgG1 in type which is non-inflammatory. It has the potential to delay or prevent AD in at risk persons for AD patients who are still asymptomatic.
BNTX: Can you provide some insight into your research and where work with the vaccine stands today?
RR: Additional pre-clinical studies need to be completed in additional animal models to show it is equally effective and non-inflammatory in these species. The data then need to be presented to the FDA for evaluation and obtain permission to conduct a Phase 1 clinical trial in patients.
BNTX: What are next steps in the process of moving towards clinical trials?
RR: Completion of the FDA required pre-clinical studies.
BNTX: There are differing theories on what causes Alzheimer’s, ranging from genetics to environmental conditions. What causes and factors do you believe have the greatest impact on the rise of Alzheimer’s disease, and do you believe that, outside of a vaccine, there is any hope for developing more preventative-oriented best practices for people to avoid the disease?
RR: Our aging population is the greatest risk factor. Americans with AD number about 6 million and that number will double in about 20 years if no effective therapy is developed. Aging and AD at risk genes are the cause of AD. They are not easily treated. There are co-morbidities that add to the rate and degree of dementia that are treatable including obesity, hypertension, cardiovascular disease, diabetes, lack of aerobic exercise and elevated blood lipids. These measures will delay the onset of dementia and reduce its severity but will not prevent it.
BNTX: In trying to mitigate Alzheimer’s, patients and their families have direct contact with their physicians, but rarely have any interaction with researchers. How does the research phase of treating and curing a disease like Alzheimer’s interact with the clinical services that patients ultimately receive?
RR: When the FDA approves testing the vaccine on patients, a clinical trial will be designed by our research group and clinical neurologists who will follow and care for the patients during the trial measuring its effectiveness and monitoring for potential side-effects. It will be a close collaboration between the researchers who developed the vaccine and physicians implementing the clinical trial.
BNTX: What is your interaction with the clinical side of Alzheimer’s treatment at UT Southwestern, if any, and how does the research and clinical arms of treating the disease complement one another?
RR: I see patients regularly each week. I also am actively involved in clinical trials currently testing new therapies for their effectiveness and any side-effects. I have been directly involved in both basic research for AD and seeing patients with AD and doing clinical trials for 25 years. Going from the research bench to the patient bedside, and vise-versa, is an important transition to keep intact scientific skills and clinical acumen about the disease. Insights and ideas occur by keeping this process active!
UT Southwestern: Where Research & Clinical Care Are Combining For An Alzheimer’s Cure
Dr. Rosenberg concludes his interview with an eye-opening revelation that the hands-on clinical care that Alzheimer’s patents receive is inextricably connected with researchers such as himself, who work both ends of the process to develop a cure for Alzheimer’s. What is developed in the lab and what is used to treat Alzheimer’s are not mutually exclusive of one another — the lab and clinic work in tandem to deliver state-of-the-art treatment for Alzheimer’s.
This is precisely why having a world-class research center leads to world-class Alzheimer’s care.
Alzheimer’s care at UT Southwestern is provided through its nationally-ranked clinical neurosciences interdisciplinary programs, which offers a wide-ranging, unprecedented suite of world-renowned health practitioners and neurologic care, including:
- Neuroradiology and imaging
- Physical medicine and rehabilitation
If you’re looking for more information about how UT Southwestern help you or a loved one with Alzheimer’s Disease, be sure to visit the Medical Center’s Alzheimer’s and Memory Disorders by clicking the icon below:
Roger Rosenberg, M.D.
University of Texas Southwestern
World Health Organization
Policy Brief: The Global Impact of Dementia 2013-2050 – Alzheimer’s Disease International