Cannabidiol as a putative novel therapy for diabetic retinopathy

A postulated mechanism of action as an entry point for biomarker-guided clinical development

G. I. Liou, A. B. El-Remessy, A. S. Ibrahim, R. B. Caldwell, Y. M. Khalifa, A. Gunes, J. J. Nussbaum

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Diabetic retinopathy is a leading cause of blindness in the Western world. However, treatment options for diabetic retinopathy are limited and display poor efficacy with marked patient-to-patient variation in therapeutic outcomes. Discovery of new molecular entities acting on mechanistically novel biological pathways remains as one of the key research priorities in diabetic retinopathy. Moreover, given the variable success of the existing treatment modalities, a targeted and personalized drug development strategy could be more fruitful for rational and successful transition of preclinical discoveries to the clinical realm. This review is focused on cannabidiol, a non-psychoactive native cannabinoid, as an emerging and novel therapeutic modality based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy - one of the retinal diseases associated with vascular neuroinflammation. We present the postulated and preclinically documented novel mechanisms that may underlie cannabidiol mode of action in diabetic retinopathy. We discuss the interindividual variation in pharmacokinetic pathways as well as in the SLC29A1 gene, a molecular target for cannabidiol. We emphasize that the novel mode of action of cannabidiol and the previous failures with nontargeted interventions in diabetic retinopathy collectively demand a more rational and personalized clinical development strategy for compounds that have shown promise at the preclinical stage. Moreover, it is noteworthy that ophthalmology, as a medical specialty, has fewer examples (e.g., compared to oncology) of personalized medicine and biomarker applications thus far. Understanding the biological action of cannabidiol in preclinical studies is therefore a rational first step to proactively map the pertinent biomarker strategies in clinical proof of concept studies in diabetic retinopathy, and to allow advances at the hitherto neglected intersection of personalized medicine and ophthalmology.

Original languageEnglish (US)
Pages (from-to)215-222
Number of pages8
JournalCurrent Pharmacogenomics and Personalized Medicine
Volume7
Issue number3
DOIs
StatePublished - Sep 1 2009

Fingerprint

Cannabidiol
Diabetic Retinopathy
Biomarkers
Retinal Diseases
Precision Medicine
Ophthalmology
Therapeutics
Western World
Cannabinoids
Blindness
Blood Vessels
Animal Models
Pharmacokinetics
Medicine

Keywords

  • Anti-inflammation
  • Cannabidiol
  • Diabetic retinopathy
  • Drug mode of action and biomarkers
  • Targeted intervention

ASJC Scopus subject areas

  • Genetics
  • Molecular Medicine
  • Pharmacology
  • Molecular Biology
  • Genetics(clinical)

Cite this

Cannabidiol as a putative novel therapy for diabetic retinopathy : A postulated mechanism of action as an entry point for biomarker-guided clinical development. / Liou, G. I.; El-Remessy, A. B.; Ibrahim, A. S.; Caldwell, R. B.; Khalifa, Y. M.; Gunes, A.; Nussbaum, J. J.

In: Current Pharmacogenomics and Personalized Medicine, Vol. 7, No. 3, 01.09.2009, p. 215-222.

Research output: Contribution to journalArticle

@article{e8d4948f4f7c41338dcca268a47450c9,
title = "Cannabidiol as a putative novel therapy for diabetic retinopathy: A postulated mechanism of action as an entry point for biomarker-guided clinical development",
abstract = "Diabetic retinopathy is a leading cause of blindness in the Western world. However, treatment options for diabetic retinopathy are limited and display poor efficacy with marked patient-to-patient variation in therapeutic outcomes. Discovery of new molecular entities acting on mechanistically novel biological pathways remains as one of the key research priorities in diabetic retinopathy. Moreover, given the variable success of the existing treatment modalities, a targeted and personalized drug development strategy could be more fruitful for rational and successful transition of preclinical discoveries to the clinical realm. This review is focused on cannabidiol, a non-psychoactive native cannabinoid, as an emerging and novel therapeutic modality based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy - one of the retinal diseases associated with vascular neuroinflammation. We present the postulated and preclinically documented novel mechanisms that may underlie cannabidiol mode of action in diabetic retinopathy. We discuss the interindividual variation in pharmacokinetic pathways as well as in the SLC29A1 gene, a molecular target for cannabidiol. We emphasize that the novel mode of action of cannabidiol and the previous failures with nontargeted interventions in diabetic retinopathy collectively demand a more rational and personalized clinical development strategy for compounds that have shown promise at the preclinical stage. Moreover, it is noteworthy that ophthalmology, as a medical specialty, has fewer examples (e.g., compared to oncology) of personalized medicine and biomarker applications thus far. Understanding the biological action of cannabidiol in preclinical studies is therefore a rational first step to proactively map the pertinent biomarker strategies in clinical proof of concept studies in diabetic retinopathy, and to allow advances at the hitherto neglected intersection of personalized medicine and ophthalmology.",
keywords = "Anti-inflammation, Cannabidiol, Diabetic retinopathy, Drug mode of action and biomarkers, Targeted intervention",
author = "Liou, {G. I.} and El-Remessy, {A. B.} and Ibrahim, {A. S.} and Caldwell, {R. B.} and Khalifa, {Y. M.} and A. Gunes and Nussbaum, {J. J.}",
year = "2009",
month = "9",
day = "1",
doi = "10.2174/1875692110907030215",
language = "English (US)",
volume = "7",
pages = "215--222",
journal = "Current Pharmacogenomics and Personalized Medicine",
issn = "1875-6921",
publisher = "Bentham Science Publishers B.V.",
number = "3",

}

TY - JOUR

T1 - Cannabidiol as a putative novel therapy for diabetic retinopathy

T2 - A postulated mechanism of action as an entry point for biomarker-guided clinical development

AU - Liou, G. I.

AU - El-Remessy, A. B.

AU - Ibrahim, A. S.

AU - Caldwell, R. B.

AU - Khalifa, Y. M.

AU - Gunes, A.

AU - Nussbaum, J. J.

PY - 2009/9/1

Y1 - 2009/9/1

N2 - Diabetic retinopathy is a leading cause of blindness in the Western world. However, treatment options for diabetic retinopathy are limited and display poor efficacy with marked patient-to-patient variation in therapeutic outcomes. Discovery of new molecular entities acting on mechanistically novel biological pathways remains as one of the key research priorities in diabetic retinopathy. Moreover, given the variable success of the existing treatment modalities, a targeted and personalized drug development strategy could be more fruitful for rational and successful transition of preclinical discoveries to the clinical realm. This review is focused on cannabidiol, a non-psychoactive native cannabinoid, as an emerging and novel therapeutic modality based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy - one of the retinal diseases associated with vascular neuroinflammation. We present the postulated and preclinically documented novel mechanisms that may underlie cannabidiol mode of action in diabetic retinopathy. We discuss the interindividual variation in pharmacokinetic pathways as well as in the SLC29A1 gene, a molecular target for cannabidiol. We emphasize that the novel mode of action of cannabidiol and the previous failures with nontargeted interventions in diabetic retinopathy collectively demand a more rational and personalized clinical development strategy for compounds that have shown promise at the preclinical stage. Moreover, it is noteworthy that ophthalmology, as a medical specialty, has fewer examples (e.g., compared to oncology) of personalized medicine and biomarker applications thus far. Understanding the biological action of cannabidiol in preclinical studies is therefore a rational first step to proactively map the pertinent biomarker strategies in clinical proof of concept studies in diabetic retinopathy, and to allow advances at the hitherto neglected intersection of personalized medicine and ophthalmology.

AB - Diabetic retinopathy is a leading cause of blindness in the Western world. However, treatment options for diabetic retinopathy are limited and display poor efficacy with marked patient-to-patient variation in therapeutic outcomes. Discovery of new molecular entities acting on mechanistically novel biological pathways remains as one of the key research priorities in diabetic retinopathy. Moreover, given the variable success of the existing treatment modalities, a targeted and personalized drug development strategy could be more fruitful for rational and successful transition of preclinical discoveries to the clinical realm. This review is focused on cannabidiol, a non-psychoactive native cannabinoid, as an emerging and novel therapeutic modality based on systematic studies in animal models of inflammatory retinal diseases including diabetic retinopathy - one of the retinal diseases associated with vascular neuroinflammation. We present the postulated and preclinically documented novel mechanisms that may underlie cannabidiol mode of action in diabetic retinopathy. We discuss the interindividual variation in pharmacokinetic pathways as well as in the SLC29A1 gene, a molecular target for cannabidiol. We emphasize that the novel mode of action of cannabidiol and the previous failures with nontargeted interventions in diabetic retinopathy collectively demand a more rational and personalized clinical development strategy for compounds that have shown promise at the preclinical stage. Moreover, it is noteworthy that ophthalmology, as a medical specialty, has fewer examples (e.g., compared to oncology) of personalized medicine and biomarker applications thus far. Understanding the biological action of cannabidiol in preclinical studies is therefore a rational first step to proactively map the pertinent biomarker strategies in clinical proof of concept studies in diabetic retinopathy, and to allow advances at the hitherto neglected intersection of personalized medicine and ophthalmology.

KW - Anti-inflammation

KW - Cannabidiol

KW - Diabetic retinopathy

KW - Drug mode of action and biomarkers

KW - Targeted intervention

UR - http://www.scopus.com/inward/record.url?scp=72449163526&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=72449163526&partnerID=8YFLogxK

U2 - 10.2174/1875692110907030215

DO - 10.2174/1875692110907030215

M3 - Article

VL - 7

SP - 215

EP - 222

JO - Current Pharmacogenomics and Personalized Medicine

JF - Current Pharmacogenomics and Personalized Medicine

SN - 1875-6921

IS - 3

ER -