Detection of traumatic brain injury
Inventors
Patel, Sarjubhai • Rau, Thomas
Assignees
University of Montana Missoula
Publication Number
US-9605315-B2
Publication Date
2017-03-28
Expiration Date
2035-03-26
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
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 invention provides minimally invasive methods for detecting, diagnosing, and assessing neuronal damage associated with traumatic brain injury (TBI) or chronic traumatic encephalopathy (CTE) through the evaluation of specific species of microRNAs (miRNAs) in a biological sample. The methods involve contacting a sample such as blood, plasma, serum, or cerebral spinal fluid from a patient with at least one miR-specific oligodeoxynucleotide probe, determining the expression levels of at least one microRNA represented by SEQ ID NOs: 1-69, and comparing these levels with those from a healthy control. A fold change of 1.2 or greater between the patient and control indicates the presence of brain injury.
The problem addressed by the invention is the lack of non-invasive tools or methods to diagnose TBI-induced neuronal damage or track CTE progression at an early stage, when damage is still at the molecular or cellular level and before permanent brain damage occurs. Existing methodologies are unable to detect the biochemical and molecular changes in the brain following mild or repetitive TBI, thus impeding effective clinical decision making for individuals at risk.
The core innovation includes the use of miRNA-specific probes with at least 70% complementarity to sequences implicated in neuronal damage, quantification of miRNA changes using techniques such as PCR, Northern blot, or gene chip analysis, and the use of kits containing all necessary probes and controls. The claimed methods allow for the detection, diagnosis, and longitudinal assessment of brain injuries, including both acute and chronic events, in patients such as athletes, military personnel, and others at risk.
Claims Coverage
There are three main independent inventive features claimed in this patent: a method for detecting traumatic brain injury using miRNA probes, a minimally-invasive method for detecting traumatic brain injury using blood-based samples, and a kit for detecting a traumatic brain injury.
Detection of traumatic brain injury by miRNA expression measurement
A method that comprises the steps of: 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: 18 and 37. 2. Determining the expression level of at least one microRNA represented by SEQ ID NOs: 18 and 37 by quantifying the at least one miR-specific oligodeoxynucleotide probe. 3. Comparing the expression level with a control expression level derived from a healthy subject. A 1.2 fold or greater increase in the patient's expression level relative to the control indicates the patient has suffered a traumatic brain injury.
Minimally-invasive detection of traumatic brain injury from blood, plasma, or serum
A minimally-invasive method comprising: - Contacting a blood, plasma, or serum 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: 18 and 37; - Determining the expression level of at least one microRNA represented by SEQ ID NOs: 18 and 37; - Comparing the expression level to a control sample from a healthy subject; wherein a 1.2 fold or greater increase indicates traumatic brain injury.
Kit for detecting traumatic brain injury using miRNA-specific probes
A kit for detecting traumatic brain injury comprising: - One or more miR-specific oligodeoxynucleotide probes having at least 70% complementarity to a sequence selected from SEQ ID NOs: 18 and 37; - One or more control samples; - Instructions indicating use of the probes and control samples for detecting traumatic brain injury using steps of probing, quantification, comparison to healthy controls, and determination based on 1.2 fold or greater increase.
The inventive features encompass methods and kits for detecting traumatic brain injury through the measurement and comparison of specific miRNA levels, using minimally invasive sampling and specific probe sequences, with diagnostic determination based on defined fold changes in expression.
Stated Advantages
Allows for minimally invasive or non-invasive rapid detection, diagnosis, and assessment of neuronal damage following traumatic brain injury or chronic traumatic encephalopathy.
Enables early identification and longitudinal assessment of neuronal damage, improving clinical outcomes by guiding critical medical and behavioral decision making.
Permits the use of blood, plasma, or serum samples, facilitating easier and less invasive sample collection.
Documented Applications
Detection, diagnosis, and monitoring of neuronal damage in individuals suffering from or at risk of traumatic brain injury or chronic traumatic encephalopathy.
Clinical assessment of brain injury progression or healing over time through repeated measurement.
Use in populations at risk such as football players, boxers, military personnel, and fall victims.
Interested in licensing this patent?