Cyclosporine as Therapy for Traumatic Brain Injury
(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.
(Less)
- author
- Hansson, Magnus J. LU and Elmér, Eskil LU
- organization
- publishing date
- 2023
- 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}}, }