Treatment of neurodegenerative diseases (HD/jNCL3)
The aim of this project is to screen different plant extracts and monosubstances for their ability to attenuate pathology in mouse models of the neurodegenerative diseases Huntington’s disease (HD) and Batten disease, the juvenile form of neuronal ceroid lipofuscinosis (jNCL3).
Our research will (i) help to find new drugs against the diseases, (ii) provide valuable new insights into their pathogenesis and (iii) identify novel targets and optimal time windows for treatment of patients.
The experiments will be carried out in mice. Including experimental animals, breeding animals for experiments and strain maintenance, and siblings with undesired genotypes, this application describes the use of up to 22,988 animals. Notably, we aim to find a treatment that will ameliorate the disease and thus, potentially postpone the disease onset. Therefore, long-term monitoring of animals is absolutely necessary, but may lead to at most 120 animals reaching very old age and thereby falling into the category of severe distress. The remaining animals are expected to experience mild to moderate distress.
The 3 Rs were taken into consideration during the planning of this project. The development of neurodegenerative diseases involves a complex interplay of different cell types in three-dimensional tissues. To date, there are no in vitro models that can effectively reproduce these complex settings to deliver reliable results. Thus, animal models are required to identify therapeutic targets and optimal time windows for effective treatment of neurodegenerative diseases. Moreover, before drugs can advanced to clinical studies in humans, animal models provide an inevitable mean to exclude severe side effects. While we cannot replace certain experiments, we reduce animal numbers by phasing experiments in such a way that only research paths yielding statistically significant and thus relevant results will be pursued further, hence minimizing the number of animals needed to obtain robust results. Furthermore, all methods and animal models that we plan to use in this project have been established in our research group for a while. All treatments which can cause pain or significant stress in animals will be performed under general anaesthesia. Thus, we expect the harm inflicted on the animals to be minimal.
Our research will (i) help to find new drugs against the diseases, (ii) provide valuable new insights into their pathogenesis and (iii) identify novel targets and optimal time windows for treatment of patients.
The experiments will be carried out in mice. Including experimental animals, breeding animals for experiments and strain maintenance, and siblings with undesired genotypes, this application describes the use of up to 22,988 animals. Notably, we aim to find a treatment that will ameliorate the disease and thus, potentially postpone the disease onset. Therefore, long-term monitoring of animals is absolutely necessary, but may lead to at most 120 animals reaching very old age and thereby falling into the category of severe distress. The remaining animals are expected to experience mild to moderate distress.
The 3 Rs were taken into consideration during the planning of this project. The development of neurodegenerative diseases involves a complex interplay of different cell types in three-dimensional tissues. To date, there are no in vitro models that can effectively reproduce these complex settings to deliver reliable results. Thus, animal models are required to identify therapeutic targets and optimal time windows for effective treatment of neurodegenerative diseases. Moreover, before drugs can advanced to clinical studies in humans, animal models provide an inevitable mean to exclude severe side effects. While we cannot replace certain experiments, we reduce animal numbers by phasing experiments in such a way that only research paths yielding statistically significant and thus relevant results will be pursued further, hence minimizing the number of animals needed to obtain robust results. Furthermore, all methods and animal models that we plan to use in this project have been established in our research group for a while. All treatments which can cause pain or significant stress in animals will be performed under general anaesthesia. Thus, we expect the harm inflicted on the animals to be minimal.