Research uses animal models of ALS, mainly based on transgenic mouse lines carrying mutations of the human SOD-1 protein gene. Transgenic mice significantly improved our understanding of ALS and suggested new hypotheses about the mechanism of motor neuron diseases. However, SOD-1 mutations involve pathogenic pathways that could be very different from those involved in sporadic cases and in ALS cases linked to other mutations.
Why is research on post mortem human nervous tissue still useful ?
1. The observation of diseased human tissues makes it possible to identify hitherto undescribed lesions and to develop other hypotheses.
2. The mechanism of motor neuron impairment observed in ALS patients is still imperfectly known. TDP-43 protein is one of the main constituents of the lesions in most cases, but other molecules, maybe crucial for the development of the disease, have also been found in the lesions; many of those remain to be discovered.
3. All the models are incomplete. The analysis of human tissues remain essential and has to be confronted with the data obtained from experimental models.
4. ALS may be a common syndrome for several diseases requiring different treatments. One of the next challenges will be to evaluate whether the new molecules modify the lesions and their progression in the nervous system. A collection of well-studied samples will be essential to improve the therapeutic approach.