Defining the role of schwann cell precursors in neural repair.
Canadian Institutes of Health Research
- Grant type: CIHR Fellowship
- Years: 2015/16 to 2018/19
- Total Funding: $135,000
- AMYOTROPHIC LATERAL SCLEROSIS
- AMYOTROPHIC LATERAL SCLEROSIS (ALS)
- Cell biology
- INDUCED PLURIPOTENT STEM CELLS
- IN VITRO CO-CULTURE
- Molecular biology
- NERVOUS SYSTEM
- SPINAL CORD DISEASE
Toma, Jeremy S
No researchers found.
No partner organizations found.
Amyotrophic lateral sclerosis (ALS) is a devastating disease whereby the progressive degeneration and death of motoneurons ultimately results in paralysis due to loss of muscle control. Recent research has led to findings that indicate that the region where motoneurons connect to muscles, known as the neuromuscular junction (NMJ), is critical in the development of the disease. This research has revealed two alterations in communication between motoneurons and muscle that are likely early modifying factors in ALS. They include: i) alterations in the transport of important gene products from the motoneuron's cell body within the spinal cord, to the motor nerve ending within muscle. These gene products make specific proteins needed for motoneurons to effectively contract muscle; and ii) a decline in the signalling between motor nerves and muscle that stabilizes their connections. The proposed project will address these two types of alterations at the NMJ in ALS using a variety of state-of-the-art techniques. First, we propose to re-construct the human neuromuscular circuit in culture from cells derived from ALS and healthy control patients. We will utilize an established technique that allows skin cells from ALS and control patients to be converted into both muscle and motoneurons. These cell types will subsequently be cultured together to form motoneuron-muscle connections. By assessing the movement of gene products (and the proteins that interact with them) within the motor neuron and its nerve terminal ending and measuring the stability of neuromuscular connections over time, we will be able to gain unprecedented insight into the causes of ALS. In the process, we will also establish a novel drug-screening platform for ALS, which could result in therapeutic benefits for improving muscle function in patients with ALS.