Dr Catherina Becker

Centre for Neuroregeneration

Edinburgh

Motor neuron diseases (MNDs) are characterized by a progressive loss of motor neurons, the cells which are responsible for all muscle movement. MNDs are often fatal, because motor neurons never regenerate. There is therefore an unmet need for therapies that prevent motor neuron death and/or stimulate regeneration of lost motor neurons. We are using the zebrafish as a model organism to find drugs that modulate de- and re-generation of motor neurons, because adult zebrafish have the astounding capability to regenerate motor neurons. Furthermore, because of their small size, zebrafish embryos can be used for drug screening.

We have already found a drug that promotes motor neuron regeneration in a spinal lesion model and protects mammalian motor neurons from degeneration. In this project we aim to establish lesion models that selectively injure motor neurons, because the action of drugs can be more precisely assessed than after a spinal lesion, which elicits a large number of different molecular and cellular processes. We plan to: 

  1. Generate transgenic fish that contain an enzyme that activates a toxin only in motor neurons
  2. Slowly kill motor neurons with toxins known to preferentially cause oxidative stress in motor neurons, which would be very similar to the mechanisms of motor neuron death in MNDs
  3. Test our newly found drugs in these models for their ability to protect motor neurons and promote their regeneration. Our analyses aims to find drugs that ultimately could lead to new therapeutic approaches to MNDs.
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