Cardiovascular and organ pathology in spinal muscular atrophy

Spinal muscular atrophy is a fatal, childhood form of motor neurone disease, where death of the motor neurons, if untreated, results in paralysis followed by respiratory failure and premature death. SMA is now treatable, and patient survival and health are improving, but evidence suggest that we are not treating the whole disease.

It is now clear that the cell-ubiquitous depletion of the SMN protein, which is the cause of spinal muscular atrophy, results in a wide range of tissue pathologies beyond the motor neuron. Our work has revealed the extent of these systemic defects and is beginning to appreciate how they impact upon the disease. We are particularly interested in the microvascular system, and have reported extensive, cell-intrinsic defects in endothelial cells and in blood vessels in animal models and patients. Our work is focussed on understanding how SMN-depletion leads to blood vessel pathology, which affects not only tissue oxygenation, but also essential barriers such as the blood brain and blood spinal cord barriers.  Specifically, we want to know if these pathologies exacerbate SMA pathology, and if so whether they can be targeted therapeutically.