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Neuroanatomic Propagation of ALS within the Spinal Cord

What is being modeled?
Disease progression of ALS in the spinal cord
Description & purpose of resource

Amyotrophic lateral sclerosis (ALS) is the most common Motor Neuron Disease. It is a progressive neurodegenerative disease that affects motor neurons in the brain and the spinal cord. The progressive degeneration of motor neurons in the spinal cord causes patients to lose their ability to control their muscle movement. As the disease progresses they lose the ability to move their limbs, speak, eat, and eventually breath, leading to death. It is the most lethal of the common neurodegenerative disorders, and has thus far been refractory to all treatments. Recent hypotheses of ALS progression have posited a point-source origin of motor neuron death with neuroanatomic propagation either contiguously to adjacent regions, or along networks via axonal and synaptic connections. Although the molecular mechanisms of propagation are unknown, one leading hypothesis is a "prion-like" spread of misfolded and aggregated proteins.

To better understand this devastating disease, we are developing a cellular and molecular scale computational model of the spread of ALS within the spinal cord. We parametrized our stochastic reaction-­diffusion SIR style model by reconstructing human spinal cord from high­-resolution magnetic resonance (MR) images and known gross and histological neuroanatomy. Our model appears to realistically recapitulate the clinical and pathological spread of ALS in human spinal cord. We are using the model combined with clinical assessment data to quantify and characterize the cellular and molecular spread of ALS, predict the relative contributions of network and contiguous spread, and attempt to explain the differential cellular vulnerability to the disease.

Spatial scales
Temporal scales
weeks to months
This resource is currently
under early-stage development
a demonstration or a framework to be built upon (perhaps with a sample implementation)
Has this resource been validated?
Key publications (e.g. describing or using resource)
Brian Drawert
PI contact information
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