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Cyclosporine as Therapy for Traumatic Brain Injury

Hansson, Magnus J. LU orcid and Elmér, Eskil LU orcid (2023) In Neurotherapeutics 20(6). p.1482-1495
Abstract

Drug development in traumatic brain injury (TBI) has been impeded by the complexity and heterogeneity of the disease pathology, as well as limited understanding of the secondary injury cascade that follows the initial trauma. As a result, patients with TBI have an unmet need for effective pharmacological therapies. One promising drug candidate is cyclosporine, a polypeptide traditionally used to achieve immunosuppression in transplant recipients. Cyclosporine inhibits mitochondrial permeability transition, thereby reducing secondary brain injury, and has shown neuroprotective effects in multiple preclinical models of TBI. Moreover, the cyclosporine formulation NeuroSTAT® displayed positive effects on injury biomarker levels... (More)

Drug development in traumatic brain injury (TBI) has been impeded by the complexity and heterogeneity of the disease pathology, as well as limited understanding of the secondary injury cascade that follows the initial trauma. As a result, patients with TBI have an unmet need for effective pharmacological therapies. One promising drug candidate is cyclosporine, a polypeptide traditionally used to achieve immunosuppression in transplant recipients. Cyclosporine inhibits mitochondrial permeability transition, thereby reducing secondary brain injury, and has shown neuroprotective effects in multiple preclinical models of TBI. Moreover, the cyclosporine formulation NeuroSTAT® displayed positive effects on injury biomarker levels in patients with severe TBI enrolled in the Phase Ib/IIa Copenhagen Head Injury Ciclosporin trial (NCT01825044). Future research on neuroprotective compounds such as cyclosporine should take advantage of recent advances in fluid-based biomarkers and neuroimaging to select patients with similar disease pathologies for clinical trials. This would increase statistical power and allow for more accurate assessment of long-term outcomes.

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author
and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Biomarkers, Brain injuries, Traumatic, Clinical trials as topic, Cyclosporine, Diffuse axonal injury, Drug evaluation, Preclinical
in
Neurotherapeutics
volume
20
issue
6
pages
1482 - 1495
publisher
Springer
external identifiers
  • pmid:37561274
  • scopus:85167520123
ISSN
1933-7213
DOI
10.1007/s13311-023-01414-z
language
English
LU publication?
yes
id
2e47be2b-e587-4e82-8c58-2941e8166800
date added to LUP
2023-11-21 12:39:02
date last changed
2024-11-15 14:13:03
@article{2e47be2b-e587-4e82-8c58-2941e8166800,
  abstract     = {{<p>Drug development in traumatic brain injury (TBI) has been impeded by the complexity and heterogeneity of the disease pathology, as well as limited understanding of the secondary injury cascade that follows the initial trauma. As a result, patients with TBI have an unmet need for effective pharmacological therapies. One promising drug candidate is cyclosporine, a polypeptide traditionally used to achieve immunosuppression in transplant recipients. Cyclosporine inhibits mitochondrial permeability transition, thereby reducing secondary brain injury, and has shown neuroprotective effects in multiple preclinical models of TBI. Moreover, the cyclosporine formulation NeuroSTAT<sup>®</sup> displayed positive effects on injury biomarker levels in patients with severe TBI enrolled in the Phase Ib/IIa Copenhagen Head Injury Ciclosporin trial (NCT01825044). Future research on neuroprotective compounds such as cyclosporine should take advantage of recent advances in fluid-based biomarkers and neuroimaging to select patients with similar disease pathologies for clinical trials. This would increase statistical power and allow for more accurate assessment of long-term outcomes.</p>}},
  author       = {{Hansson, Magnus J. and Elmér, Eskil}},
  issn         = {{1933-7213}},
  keywords     = {{Biomarkers; Brain injuries, Traumatic; Clinical trials as topic; Cyclosporine; Diffuse axonal injury; Drug evaluation, Preclinical}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{1482--1495}},
  publisher    = {{Springer}},
  series       = {{Neurotherapeutics}},
  title        = {{Cyclosporine as Therapy for Traumatic Brain Injury}},
  url          = {{http://dx.doi.org/10.1007/s13311-023-01414-z}},
  doi          = {{10.1007/s13311-023-01414-z}},
  volume       = {{20}},
  year         = {{2023}},
}