In August 2017, Randolph Ashton, an assistant professor of biomedical engineering at the University of Wisconsin-Madison, received almost $800,000 from the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health, to continue a five-year research study of Lou Gehrig’s disease (amyotrophic lateral sclerosis, or ALS), after successfully completing its first phase.
The goal of the project is to grow brain and spinal cord tissues from induced pluripotent stem cells derived from ALS patients. Similar to embryonic stem cells, induced pluripotent stem cells can grow indefinitely and give rise to every cell type in the human body, but are created from adult cells.
Ashton hopes to shed light on the cellular mechanisms that cause ALS, with the ultimate goal of identifying and screening novel drug candidates that may slow the disease progression. ALS symptoms result from the death of motor neuron cells: specialized cells in the brain and spinal cord that send electric signals to the muscles in our jaws, arms, legs and other body parts in order to initiate movement and speech. As a result of dying motor neuron cells, ALS patients become increasingly paralyzed and lose the ability to speak and breathe. Most patients succumb to the disease within a few years of onset.
During the first phase of the project, Ashton began to develop a novel tissue engineering platform that supports the long-term growth of multiple diverse cell types to mimic a human spinal cord. During the next phase, he will optimize this platform and use it to build genotype-specific disease models, where the death of motor neuron cells is induced by specific mutations in a gene called SOD1.
This gene has long been known to cause familial forms of ALS and has been the basis of many rodent models for the disease. Since the tissue-engineered system Ashton is building starts with human cells, it has the potential to more accurately mimic the human disease process than traditional animal models.