Blood Brain Marker Development for Prognosis in Recovery from Stroke

Rajiv R. Ratan, M.D., Ph.D.

Weill Medical College of Cornell University

Neurology and Neuroscience
Funded in December, 2007: $100000 for 3 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY .

LAY SUMMARY

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Exploring potential biomarkers’ utility for making prognosis of stroke recovery

A team of investigators will determine whether any of several biologic factors may help to predict patients’ recovery from ischemic stroke.  These are strokes that result from lack of adequate blood flow to the brain due to a blood clot. Identifying brain-related predictors of recovery would enable clinicians to more effectively determine a rehabilitation strategy that maximizes each patient’s potential outcomes. Each of the several biological factors to be studied can be identified in patients’ blood samples. The investigators will obtain blood samples from 400 patients at the time of their admission to Burke Rehabilitation Institute and thereafter at weekly intervals until they are discharged.
The blood samples will be analyzed to determine if a panel of markers can distinguish those who recover function from ischemic stroke compared to those who do not. Additionally, the investigators will establish a system for “banking” each patient’s DNA and RNA, for use in future efforts to discover predictors of recovery that are based on analyses of patients’ genes and the proteins genes produce, in case the currently identified factors fail to predict stroke recovery.   
If any of the factors are found to statistically correlate with improved stroke recovery, future rehabilitation strategies for individual patients would be based on analyses of these factors.  This process could potentially help patients regain stroke-impaired speech, language, and arm and leg functions.

ABSTRACT

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Blood Biomarkers for Recovery from Stroke

Stroke is the leading cause of disability and loss of independence in the United States.  The American Heart Association estimates the economic cost of stroke at $62.7 billion in 2007. Yet there are currently no blood tests that accurately predict who will or will not recover from stroke.
We are proposing an exciting breakthrough study to develop blood markers to aid in prognosis for recovery following a stroke. If successful, such blood markers could help identify the best treatments in regenerating the nervous system and the patients who would benefit the most.
We have identified a panel of putative biomarkers in the blood of stroke patients that could help assess those most likely to experience neurological recovery.  Having the ability to accurately determine biomarkers for neuronal recovery may be a breakthrough for stroke recovery treatment as they offer the ability to track the progress of intervention therapy and may provide new insight into neuronal repair and recovery. This information would be invaluable for drug development.
An unfortunate reality of many acute stroke treatments is that successful results in animal models do not translate into human studies.  Our study will involve patients with a diagnosis of ischemic stroke admitted to the Burke Rehabilitation Hospital.   Blood will be taken from the patients upon admission (after informed consent), and weekly thereafter to monitor progress. The blood will be stored to allow accurate determination of candidate biomarkers (e.g., erythropoietin, brain derived neurotrophic factor, f2 isoprostanes). In parallel, a clinical database that contains information on stroke type, size, current medications and functional outcomes will be maintained.  The relevance of comorbidities such as cardiac, renal, hepatic, rheumatologic or other systemic disorders will be recorded.  Medications which may interfere with biomarker expression or measurement will also be noted.
We expect data analysis from this study will allow us to identify one or more blood tests that can predict which patients will or won’t do well in rehabilitation. These markers may also be helpful in guiding candidates for specific therapeutic regimens.
The Burke Rehabilitation Center is ideally suited for these studies.  Our campus contains not only the renowned Burke Rehabilitation Hospital but also the Winifred Masterson Medical Research Institute. These institutions work closely together to develop and provide state-of-the-art patient care and to facilitate informational exchange among research and clinical staff.  Our mission focuses on the engagement of research, development, and programs that improve medical care, reduce disability and dependency and further knowledge and understanding of disease mechanisms and causes.

INVESTIGATOR BIOGRAPHIES

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Rajiv R. Ratan, M.D., Ph.D.

Dr. Ratan is the Director of the Winifred Masterson Burke/Cornell Medical Research Institute and Burke Professor of Neurology, Neuroscience and Rehab Medicine at Weill Medical College, Cornell University.  One focus of Dr. Ratans’ lab is to develop new pharmacological approaches for preventing or ameliorating disability from nervous system conditions. A stroke, spinal cord injury, or other neurological disease will cause neurons to die, which in turn, adversely influences recovery.  Much of this neuronal death is caused by highly reactive molecules, called free radicals.  Dr. Ratans’ lab is developing “drugs” to augment the body’s natural defenses to free radicals. These drugs are candidate therapies for stroke and spinal cord injury prevention and recovery. Dr. Ratan is not only a member of the Board of Directors of both The Burke Rehabilitation Hospital and the Boston ALS Therapy Alliance but he is also a member of the Scientific Advisory Board of The Boston Cure Project. He is on the Editorial Boards of Antioxidants and Redox Signaling, NeuroRx, The Journal of Neuroscience, Stroke and Neurobiology of Disease. Dr Ratan has written over 60 peer reviewed publications.   Dr Ratan received his M.D. and Ph.D. degrees from New York University where he was awarded numerous honors. Before joining Burke, he was an Assistant Professor in the Departments of Neurology and Physical Medicine and Rehabilitation at The Johns Hopkins University School of Medicine and an Associate Professor in the Department of Neurology at Harvard Medical School.