Innate immune proteins as biomarkers for CNS injury
Inventors
KEANE, ROBERT W. • Dietrich, W. Dalton • De Rivero Vaccari, Juan Pablo • Adamczak, Stephanie • Bullock, M. Ross • Levi, Allan • Wang, Michael Y.
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Assignees
MemberUniversity of MiamiUniversity of MiamiThe University of Miami, established in 1925 and based in Coral Gables, Florida, is a private research university recognized for its comprehensive academic offerings, robust research infrastructure, and strong interdisciplinary focus. Home to more than 19,000 students and with more than 400 acres of campuses across the Miami region, its mission encompasses education, research, innovation, and community service. The institution supports clinical, biomedical, marine, and atmospheric research initiatives, delivers diverse undergraduate and graduate programs, and maintains numerous research centers and institutes dedicated to scientific, medical, and societal advancements.
The University of Miami, established in 1925 and based in Coral Gables, Florida, is a private research university recognized for its comprehensive academic offerings, robust research infrastructure, and strong interdisciplinary focus. Home to more than 19,000 students and with more than 400 acres of campuses across the Miami region, its mission encompasses education, research, innovation, and community service. The institution supports clinical, biomedical, marine, and atmospheric research initiatives, delivers diverse undergraduate and graduate programs, and maintains numerous research centers and institutes dedicated to scientific, medical, and societal advancements.
Publication Number
US-12560618-B2
Publication Date
2026-02-24
Expiration Date
Abstract
The present invention provides novel markers of the severity of a central nervous system injury, such as spinal cord injury or traumatic brain injury, in a patient. In particular, protein components of inflammasomes in the cerebrospinal fluid that can be used to assess the severity of central nervous system injury in a patient are disclosed. Methods of using such protein biomarkers to determine a prognosis, direct treatment and rehabilitation efforts, and monitor response to treatment for a patient with a central nervous system injury are also described.
Core Innovation
The invention relates to evaluating and treating patients suspected of having a spinal cord injury or traumatic brain injury by using cerebrospinal fluid (CSF) to detect inflammasome proteins. The method provides a biological sample from a patient presenting clinical symptoms consistent with spinal cord injury or traumatic brain injury, wherein the biological sample is CSF.
Levels of at least one inflammasome protein in the CSF are measured by immunoblot or ELISA. The at least one inflammasome protein is selected from nucleotide-binding leucine-rich repeat pyrin domain containing protein 1 (NLRP1), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1, including caspase-1 p20 subunit, or combinations thereof.
A protein signature associated with spinal cord injury or traumatic brain injury is determined based on an elevated level of the measured inflammasome protein relative to a predetermined reference value or range in a non-trauma patient as a control. Patients exhibiting the presence of the protein signature are selected for administration of a neuroprotective treatment when the protein signature is identified.
The invention further provides a method of determining prognosis and treating the patient by measuring inflammasome protein levels in CSF obtained within a week of injury. When measured relative to non-trauma reference values or ranges, elevated inflammasome protein levels are indicative of poor prognosis and reduced inflammasome protein levels are indicative of better prognosis, and neuroprotective treatment is administered when an elevated protein signature is identified.
Claims Coverage
Two independent claims are provided. They cover evaluating suspected spinal cord injury or traumatic brain injury and selecting neuroprotective treatment based on an inflammasome protein signature, and determining prognosis using CSF inflammasome protein levels relative to non-trauma reference values, followed by neuroprotective treatment when an elevated protein signature is identified.
CSF inflammasome protein signature for diagnosing suspected injury and selecting neuroprotective treatment
Providing CSF from a patient suspected of spinal cord injury or traumatic brain injury; measuring levels of at least one inflammasome protein by immunoblot or ELISA, wherein the at least one inflammasome protein is selected from NLRP1, ASC, and caspase-1 or a combination thereof; determining presence or absence of a protein signature associated with spinal cord injury or traumatic brain injury based on an elevated level relative to a predetermined reference value or range in a non-trauma patient control; selecting patients exhibiting presence of the protein signature; and administering a neuroprotective treatment when said protein signature is identified.
Prognosis by non-trauma-referenced CSF inflammasome protein levels and treatment for elevated signature
Providing CSF obtained within a week of injury; measuring levels of at least one inflammasome protein by immunoblot or ELISA relative to a predetermined reference value or range in a non-trauma patient control, wherein elevated measured inflammasome protein indicates poor prognosis and reduced measured inflammasome protein indicates better prognosis; and administering a neuroprotective treatment when said elevated protein signature is identified.
The independent claims define diagnosis/evaluation and prognosis using CSF inflammasome protein levels (NLRP1, ASC, caspase-1 and optionally caspase-1 p20) measured by immunoblot or ELISA and compared to non-trauma predetermined reference values or ranges. Elevated levels support identification of an injury-associated protein signature and poor prognosis, and trigger administration of a neuroprotective treatment.
Stated Advantages
Enables evaluating suspected spinal cord injury or traumatic brain injury using an inflammasome protein signature.
Supports selecting patients for neuroprotective treatment when the protein signature is identified.
Provides prognosis based on CSF inflammasome protein levels compared to non-trauma reference values.
Supports administering neuroprotective treatment when an elevated protein signature is identified for poor prognosis.
Documented Applications
Use of CSF inflammasome protein measurement to evaluate and treat a patient suspected of spinal cord injury or traumatic brain injury.
Use of CSF inflammasome protein measurement to determine prognosis for a patient with spinal cord injury or traumatic brain injury and treat when an elevated protein signature is identified.
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