Forsøksdyr: Pilot Aminoacridine Tox Hamster

Godkjenningsdato 02.11.2020

Godkjenningsperiode 02.11.2020-31.12.2021

1. Purpose: The overall aim of the project is to determine the efficacy of certain proprietary 9-aminoacridines drug candidates on viral pneumonia caused by SARS-Cov2 infection in golden syrian hamsters (Covid-19 animal model giving a similar but milder phenotype as in humans and developed by the Wageningen Bioveterinary Research Institute (WBVR), the Netherlands as part of the WHO Covid-19 working group for animal models). This pilot aims to assess the tolerance and toxicity of 9-aminoacridines on the golden Syrian hamsters, prior to a larger experiment testing the effect in the Covid-19 hamster model in the WBVR BSL-3 facility

2. Distress: The 9-aminoacridine we will administer to the animals has to our knowledge not been used in animals before. However, this drug is chemically similar to Quinacrine, which has been in use for humans (still used to treat certain rheumatoid diseases). In hamsters, the lowest lethal dose (LDLo) of quinacrine has been determined as 80 mg/Kg with intraperitoneal injections and the LD50 dose for intraperitoneal injections in mice is 189mg/Kg. We plan to inject 50 mg/Kg or less, well below the lowest lethal dose of Quinacrine, but as the actual compounds to be tested here have not been examined for toxicity, we wish to examine the effect of the drug to observe any potential adverse effects before doing a very important and expensive efficacy study at the WBVR BSL-3 facility. Hence, the determination of possible toxicity and adverse effects is the aim of this project. The adverse effects of this compound are unknown, but they may be similar to those of quinacrine which includes gastrointestinal and dermatologic reactions, and in severe cases hematological effects like aplastic anemia and neurological effects like psychosis and restlessness can potentially occur. Through close monitoring and use of a scoring scheme, the severity will be limited to maximum short-term moderate pain or long-term mild pain.

3. Expected scientific benefits: This pilot will enable us to perform subsequent experiments assessing the efficacy of 9-aminoacridines on the viral pneumonia caused by Covid-19 in golden syrian hamsters, which may have potential important therapeutic effects in humans.

4. Number of animals and species: We are applying for an experiment with 30 golden syrian hamsters (Mesocricetus auratus)

5. 3R: Assessing the toxicity of 9-aminoacridines on a limited number of animals will give us valuable information for the upcoming larger scale experiment assessing the efficacy of 9-aminoacridines in Covid-19. Based on potential findings in this experiment we would be able to adjust the administration scheme and drug concentrations in future Experiments, elevating the welfare of future animals and potentially reducing animals that may otherwise be used without conclusion due to toxic levels of drug treatments.