Lou Gehrig's disease, also known as amyotrophic lateral sclerosis, is a progressive disease that affects nerve cells in the brain and the spinal cord. The condition gradually attacks nerve cells that control the individual’s voluntary movement, leading to paralysis and death.

Until now, scientists were unable to identify the origin of this condition that affects 30,000 individuals in the United States. Released in the journal Cell Stem Cell, the researchers from the University of Wisconsin-Madison believe they found a genetic mutation in a small group of patients with amyotrophic lateral sclerosis.

The approach to transfer that gene to animals from drug testing has not worked yet. Su-Chun Zhang, a neuroscientist at the Waisman Center at UW-Madison, has been using a different approach by studying diseased human cells in lab dishes. Those cells, called motor neurons, direct muscles to contract and are the site of failure in amyotrophic lateral sclerosis. 

Ten years ago, Zhang was the first scientist to grow motor neurons from human embryonic stem cells. He recently updated that approach by transforming skin cells into iPS (induced pluripotent stem) cells, which then transform into motor neurons.

He explains that the iPS cells can be used as models for diseases, because they have many of the same traits as their donor cells.

“With iPS, you can take a cell from any patient, and grow up motor neurons that have ALS,” Zhang clarifies. “That offers a new way to look at the basic disease pathology.”

Previous studies helped scientists understand that with amyotrophic lateral sclerosis, so-called tangles - deformed proteins - along the nerve's tracks, block the course along the nerve fibers, which eventually results in faulty nerve fiber and eventually dying.

Now, the research team focused and discovered the source of these tangles.

Zhang adds that the neurofilament, a transport system inside motor neurons, plays both a structural and a functional role, “Like the studs, joists and rafters of a house, the neurofilament is the backbone of the cell, but it's constantly changing. These proteins need to be shipped from the cell body, where they are produced, to the most distant part, and then be shipped back for recycling. If the proteins cannot form correctly and be transported easily, they form tangles that cause a cascade of problems.” 

The researchers note that similar tangles occur in neurofilaments with Alzheimer's and Parkinson's diseases and believe they are looking at the source of many neurodegenerative disorders.

Additional Resource:

Modeling ALS with iPSCs Reveals that Mutant SOD1 Misregulates Neurofilament Balance in Motor Neurons