Acute Radiation Effects, the H-ARS in the Non-human Primate: A Review and New Data for the Cynomolgus Macaque with Reference to the Rhesus Macaque

Farese, Ann M.; Drouet, M.; Hérodin, Françis; Bertho, Jean-Marc; Thrall, Karla D.; Authier, Simon; Doyle-Eisele, Melanie; MacVittie, Thomas J.

doi:10.1097/hp.0000000000001442

Cited by 7 publications

(6 citation statements)

References 74 publications

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Section: Study Backgroundmentioning

confidence: 99%

“…In another instance, a shift from rhesus to cynomolgus macaques for MCM testing for radiation indications has been necessitated due to the severe scarcity of the rhesus monkeys, but it is unclear what this will mean for current work and approved models; particularly because variations in species (physical or genetic variability) can result in unexpected and non-reproducible results. 131 While the objective of clinical development is to achieve reproducible and biologically relevant data, the elements that go into this (test system, challenge material, test article, and endpoints) can have variability, which creates unanticipated challenges during development. 132 Clinical translation challenges include: (1) manifestation of injury cannot always be directly monitored in animals, (2) endpoints are not always practical, (3) animals cannot comply with dosing instructions, and (4) inadequate infrastructure and trained workforces.…”

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confidence: 99%

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Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin

Satyamitra,

Andres,

Bergmann

et al. 2023

Disaster med. public health prep.

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Purpose: To summarize presentations and discussions from the 2022 trans-agency workshop titled “Overlapping Science in Radiation and Sulfur Mustard (SM) Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures.” Methods: Summary on topics includes: 1) an overview of the radiation and chemical countermeasure development programs and missions; 2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses. Results: There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, U.S. Government program officials and regulators to discuss lung-, and skin-specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries. Conclusions: Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall U.S. Government emergency preparedness.

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Section: Study Backgroundmentioning

confidence: 99%

mentioning

confidence: 99%

Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin

Satyamitra,

Andres,

Bergmann

et al. 2023

Disaster med. public health prep.

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“…A potential more near-term solution is the use of the cynomolgus subspecies, Macaca fasicularis . Included herein is a comparative review of radiation effects between rhesus and cynomolgus macaques (Farese et al 2021).…”

Section: Animal Models Exposure Context For MCM Developmentmentioning

confidence: 99%

Animal Models: A Non-human Primate and Rodent Animal Model Research Platform, Natural History, and Biomarkers to Predict Clinical Outcome

2021

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“…Non-human primate (NHP) models are often used to analyze health effects and immune responses associated with exposure to ionizing radiation ( 15, 16 ). NHPs, especially Rhesus monkeys, share genetic and physiologic similarities to humans with relatively long-life span (∼25 years, average in captive) ( 17 ).…”

Section: Introductionmentioning

confidence: 99%

Longitudinal Analysis of Leukocyte Total and Differential Count of Rhesus Macaques (Macaca mulatta) after Total-Body Irradiation

Chino,

Olson,

Schaaf

et al. 2023

Radiation Research

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Archival data of leukocyte count and the differentials obtained from control and irradiated Rhesus Macaques (Macaca mulatta) were statistically analyzed to understand the long-term effect of ionizing radiation exposure. Nine animals received total-body irradiation (TBI) of 7.2–8.4 Gy at 3–4 years old. Twelve animals served as age-matched controls with no radiation exposure. The complete blood cell count dataset was obtained during regular health exams every 2–6 months for 8 years from their age of 8 to 17 years old. Linear mixed models for leukocyte, neutrophil, lymphocyte, and monocyte counts and their percentages were successfully developed. Estimated marginal means calculated based on the models revealed statistically significant elevations in leukocyte and neutrophil counts and neutrophil percentages in irradiated animals compared to the controls. Lymphocyte percentage was significantly lower in irradiated animals. Longitudinal trends for both control and irradiated animals were consistent with expected trends of aging in hematopoiesis, which is skewed towards production of myeloid lineage cells such as neutrophils and monocytes rather than lymphoid cells. Longitudinal trends from irradiated animals suggested the age-related increase in neutrophils and decrease in lymphocytes were stronger than in the controls, although the difference did not reach statistical significance. The mechanism of the long-term effects in the hematopoietic system were not investigated. However, the results suggest ionizing radiation causes long-term effects on some of the factors implicated in hematopoietic aging, possibly inducing early-onset or accelerated aging in the hematopoietic system. Extended analysis with observations including before and after the follow-up period in this study will be beneficial to understand the timeline and features of the long-term response.

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Acute Radiation Effects, the H-ARS in the Non-human Primate: A Review and New Data for the Cynomolgus Macaque with Reference to the Rhesus Macaque

Cited by 7 publications

References 74 publications

Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin

Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures: Overlapping science in radiation and sulfur mustard injuries to lung and skin

Animal Models: A Non-human Primate and Rodent Animal Model Research Platform, Natural History, and Biomarkers to Predict Clinical Outcome

Longitudinal Analysis of Leukocyte Total and Differential Count of Rhesus Macaques (Macaca mulatta) after Total-Body Irradiation

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