Micro-RNA, autoantibody and protein markers for diagnosis of neuronal injury

Abstract

Processes and materials are provided for the detection, diagnosis, or determination of the severity of a neurological injury or condition, including traumatic brain injury, multiple-organ injury, stroke, Alzeimer's disease, Pakinson disease and Chronic Traumatic Encephalopathy (CTE). The processes and materials include biomarkers detected or measured in a biological sample such as whole blood, serum, plasma, or CSF. Such biomarkers include Tau and GFAP proteins, their proteolytic breakdown products, brain specific or enriched micro-RNA, and brain specific or enriched protein directed autoantibodies. The processes and materials are operable to detect the presence of absence of acute, subacute or chronic brain injuries and predict outcome for the brain injury.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to U.S. Provisional Application Nos. 61 / 242,123 filed Sep. 14, 2009, 61 / 354,504 filed Jun. 14, 2010, 61 / 355,779 filed Jun. 17, 2010, and 61 / 380,158 filed Sep. 3, 2010, the contents of each of which are incorporated herein in its entirety.FIELD OF THE INVENTION[0002]The present invention relates to the identification of markers of traumatic brain injury (TBI) or other neurological conditions including stroke, Alzeimer's disease, Pakinson disease and Chronic Traumatic Encephalopathy (CTE). Inventive markers include autoantibodies, DNA, RNA, or miRNA that may play a role in central nervous system function and therapy. The invention also relates to diagnostic and therapeutic materials and methods, including methods for detecting biomarkers in brain injury, and the diagnostic method for aiding and monitoring the propensity or progression of brain injury.BACKGROUND OF THE INVENTION[0003]The field of clinical neu...

AI Technical Summary

Benefits of technology

The patent describes a method for detecting neurological conditions in a subject by measuring the levels of specific biomarkers in a biological sample. These biomarkers can include proteins, nucleic acids, or autoantibodies that are altered after a brain injury or other neurological condition. The levels of biomarkers are compared to those in a control sample to create a ratio that indicates the presence or absence of a neurological condition. The method can be used to detect brain injury, multiple-organ injury, stroke, or neurodegenerative disease. The patent also describes a detection agent that specifically targets GFAP, a protein associated with brain injury.

Problems solved by technology

Traumatic, ischemic, and neurotoxic chemical insult, along with generic disorders, all present the prospect of brain damage.

While the diagnosis of severe forms of each of these causes of brain damage is straightforward through clinical response testing, computed tomography (CT), and magnetic resonance imaging (MRI), the imaging diagnostics are limited by both the high cost of spectroscopic imaging and long diagnostic time.

The clinical response testing of incapacitated individuals is of limited value and often precludes a nuanced diagnosis.

Additionally, owing to the limitations of existing diagnostics, situations arise wherein a subject experiences a stress to their neurological condition but are often unaware that damage has occurred or fail seek treatment as the subtle symptoms often quickly resolve.

The lack of treatment of these mild to moderate challenges to neurologic condition of a subject can have a cumulative effect or otherwise result in a severe brain damage event, either of which have a poor clinical prognosis.

While a number of potential biochemical markers for TBI have been proposed, no definitive marker or process has been shown capable of diagnosing TBI, distinguishing between MTBI and TBI, or of demonstrating successful or therapeutic advantage of therapeutic administration.

Brain injuries are commonly difficult to treat effectively, and successful outcome commonly depends on how rapidly an individual is diagnosed with a particular injury subtype.

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