Detection of traumatic brain injury
Inventors
Patel, Sarjubhai • Rau, Thomas
Assignees
University of Montana Missoula
Publication Number
US-10202649-B2
Publication Date
2019-02-12
Expiration Date
2035-03-26
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Abstract
The present invention provides minimally invasive methods of detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). Specific species of microRNAs (miRNA), small, noncoding RNA molecules that play gene regulatory functions, are correlated with cellular damage and oxidative stress following TBI or CTE, allowing for rapid, minimally-invasive diagnosis and assessment of brain injury. The early identification and longitudinal assessment of neuronal damage in subjects suffering from or at risk of suffering from a TBI (e.g., football players, boxers, military personnel, fall victims) will improve clinical outcomes by guiding critical medical and behavioral decision making.
Core Innovation
The present invention provides minimally invasive methods and kits for the detection, diagnosis, and assessment of neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE). These methods utilize the quantification of specific microRNA (miRNA) species, small noncoding RNA molecules, which are correlated with cellular damage and oxidative stress following a TBI or CTE event. By analyzing miRNA levels in biological samples, such as blood, plasma, serum, or cerebral spinal fluid from a patient, the presence and progression of brain injury can be accurately determined.
The invention addresses the problem that there are currently no non-invasive diagnostic methods or tools available to evaluate neuronal damage caused by TBI or the progression of CTE. Existing methodologies cannot detect biochemical alterations or cellular-level damage in the brain that may occur after mild or repetitive traumatic brain events. This makes it difficult to assess the safety of returning to high-risk activities and manage long-term risks.
The core method involves contacting a biological sample from a patient with at least one miR-specific oligodeoxynucleotide probe that has at least 70% complementarity to specific miRNA sequences (SEQ ID NOs. 1-69 in general, and in claims, SEQ ID NOs. 5, 30, 41, and 54). The expression levels of these miRNAs are quantified and compared with control levels obtained from healthy subjects or tissue. A difference of at least 1.2 fold indicates the presence of brain injury. The approach allows early identification, longitudinal assessment, and the option for therapeutic intervention, including treatment with antioxidants if brain injury is detected.
Claims Coverage
There are two independent claims in the patent document, each directed to methods of detecting traumatic brain injury using miRNA probes and measuring expression levels for diagnosis and treatment.
Method of detecting traumatic brain injury by measuring specific miRNA expression and treating the injury
This inventive feature outlines a method comprising: 1. Contacting a biological sample derived from a patient with at least one miR-specific oligodeoxynucleotide probe having at least 70% complementarity to a sequence selected from SEQ ID NOs. 5, 30, 41, and 54. 2. Measuring the expression level of at least one microRNA represented by these sequences by quantifying the oligodeoxynucleotide probe in the biological sample. 3. Obtaining or measuring a control expression level of the same microRNAs in a control sample from a healthy subject or tissue. 4. Determining that the patient has suffered a traumatic brain injury if there is a 1.2-fold or greater increase in expression versus the control. 5. Treating the traumatic brain injury in patients determined to have suffered an injury.
Minimally-invasive method of detecting traumatic brain injury using blood, plasma, or serum samples
This inventive feature describes a minimally-invasive method comprising: 1. Contacting a blood, plasma, or serum sample from a patient with at least one miR-specific oligodeoxynucleotide probe having at least 70% complementarity to SEQ ID NOs. 5, 30, 41, or 54. 2. Measuring the expression level of at least one of these microRNAs by quantifying the probe in the sample. 3. Obtaining or performing a measurement of a control expression level in a control blood, plasma, or serum sample derived from a healthy subject or tissue. 4. Identifying a traumatic brain injury if the patient's sample shows a 1.2-fold or greater increase compared with the control. 5. Treating the traumatic brain injury in the identified patient.
The inventive features encompass minimally or non-invasive methods for detecting traumatic brain injury by measuring and comparing specific miRNA expression levels, and providing subsequent treatment for patients determined to have brain injury.
Stated Advantages
Provides minimally invasive or non-invasive detection, diagnosis, and assessment of brain injury, allowing for rapid clinical decision making.
Enables early identification and longitudinal assessment of neuronal damage, which can guide critical medical and behavioral decision making.
Allows for tracking progression or healing of brain injury over time by repeated measurements of miRNA expression profiles.
Facilitates targeted therapeutic intervention, such as administration of antioxidants, when brain injury is detected.
Documented Applications
Detection and diagnosis of traumatic brain injury (TBI) and chronic traumatic encephalopathy (CTE) by evaluating miRNA in biological samples.
Longitudinal monitoring of patients for progression or regression of neuronal damage after TBI or in at-risk populations, such as athletes, military personnel, or fall victims.
Guiding clinical treatment decisions, including administration of antioxidants when brain injury is identified.
Use in medical imaging and diagnosis for humans and animals suffering from, or at risk of, TBI, CTE, or related conditions.
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