Using Novel Imaging Agents as a Biomarker for ALS Progression in the fALS RAT

Research Summary

Principle Investigator: Clive Svendsen PhD

Assessing the progression of ALS in both animal models and the human condition would provide the ideal biomarker for testing novel compounds rapidly and efficiently. However, while MRI and other imaging modalities exist, they have not been fine-tuned for this neurological condition. Our rationale is that through better imaging of disease progression in ALS within individual patients, drug therapy throughput and success will be increased. The novel imaging marker project is in collaboration with GE and asks whether a novel agent that can be administered into the bloodstream can be taken up in areas of the brain that undergo early changes in ALS.  If so, this could be used as an important new diagnostic marker of the disease – and a novel biomarker to assess whether treatments may be working.

We just completed an extensive study mapping the exact progression of disease in the G93A rat model of familial ALS ( fALS) . Remarkably, this animal model of ALS reproduces many aspects of the disease, including stochastic loss of motor neurons that could start in either cervical (20%) or lumbar (80%) regions of the spinal cord – mirroring the situation in patients. GE Global Research has developed a novel superparamagnetic iron oxide (SPIO) nanoparticle for MR imaging of neuroinflammation. The agent was shown to be efficacious in brain and spinal cord imaging of acute neuroinflammation in an experimental autoimmune encephalomyelitis (EAE) model in the rat, with MR signal correlated with macrophages present within the CNS.