Spinal muscular atrophy (SMA) is a devastating motor neuron disease affecting primarily children. This disease is caused by degeneration of the cells known as motor neurons, which connect the spinal cord to muscles.
There are currently no effective treatments for SMA although a number of therapeutic options have been proposed for SMA. Such potential therapeutics have shown remarkable promise in animal models of SMA and some are currently in clinical trial.
Importantly, however, the animal model trials revealed that while administration of the therapeutic can nearly rescue an individual from the disease when given before symptoms start, the benefits are vastly reduced when therapies are given after symptom onset, even at very early stages of the disease.
As it will be likely to treat patients after symptom onset, it is very important to understand why the benefits of therapeutics are so limited after symptoms have started, and find way in which to maximize the benefits during symptomatic stages of the disease.
In this project Lyndsay and her team will use a mouse model of SMA to investigate how quickly a motor neuron can repair itself with the candidate therapeutic is given. They will then investigate what problems in the motor neurons cannot be fixed when the candidate therapeutic is given later in the disease.
Finally, they will investigate whether other drugs can be given in combination to help motor neurons repair themselves when the treatment is given during symptomatic stages of the disease.
This work has important implications for the development of therapies for SMA. It will help us understand more precisely how these candidate therapeutics affect the motor neurons. It will also help us understand what limits the benefits of the therapeutics, and will investigate ways in which to make them work better.