Human-cell-derived model of ALS provides a new way to study the majority of cases

Aug 11, 2011

For decades, scientists have studied a laboratory mouse model that develops signs of the paralyzing disease amyotrophic lateral sclerosis (ALS) as they age. In a new study appearing in Nature Biotechnology, investigators at Nationwide Children's Hospital have developed a new model of ALS, one that mimics sporadic ALS, which represents about 90 percent of all cases.

ALS, commonly known as Lou Gehrig's disease, is characterized by the death of , which are muscle-controlling in the spinal cord. As these neurons die, the body's voluntary muscles weaken and waste away; death within five years of diagnosis is common. Only about 10 percent of ALS cases are familial meaning the disease runs in the family. The majority of ALS cases are sporadic, with no family history.

Mutations in the SOD1 gene are found in about one-fifth of people with familial ALS, and for decades, experts have theorized that the gene holds clues to sporadic ALS. carrying human SOD1 mutations develop signs of ALS as they age, and have been widely used to investigate the causes and potential treatments for the disease. At the same time, however, researchers have questioned whether SOD1 mice are useful and whether SOD1 itself is relevant for understanding sporadic ALS. While dozens of potential therapies have shown promise in the mice, most have failed in patients.

"The mouse models capture a type of familial ALS that accounts for only two percent of all cases. The field has begged for new that can provide a clear window into sporadic ALS," said senior author Brian Kaspar, PhD, principal investigator in the Center for Gene Therapy of The Research Institute at Nationwide Children's Hospital.

Nationwide Children's researchers attempted to develop such a model by isolating cells from patients' spinal tissue within a few days after death.

First, the team isolated neural progenitor cells from post-mortem spinal tissue of patients with ALS. are the "parent" cells of neurons and astrocytes, cells of the central nervous system. They then coaxed these progenitor cells to develop into astrocytes. Next, the team combined the patient-derived astrocytes with mouse motor neurons. At first, the motor neurons grew normally, but after four days, they began to degenerate. By five days, the number of motor neurons reduced by about half compared to motor neurons that had been grown with control astrocytes. Similar results were seen when the motor neurons were grown with astrocytes from a patient with familial ALS, or with a cell culture broth that had been conditioned by astrocytes from any of the ALS patients. This suggests the ALS-derived astrocytes are releasing one or more unknown toxins.

Further experiments revealed that inflammatory responses and SOD1 may play a critical role in this toxicity. These results suggest that replacing astrocytes may be just as important as replacing motor neuron lost to the disease and that astrocytes and SOD1 need further investigation as targets for therapy.

"It has been a long road, but the hard work starts now," said Dr. Kaspar. "We still need to confront fundamental questions about what is happening to astrocytes and how they are killing motor neurons. And the ultimate goal is to identify therapies that will translate into helping humans."

Explore further: Heaven scent: Finding may help restore fragrance to roses

Related Stories

Researchers discover genetic link between both types of ALS

May 05, 2010

Researchers from Northwestern University Feinberg School of Medicine have discovered a link between sporadic and familial forms of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease also known as Lou Gehrig's ...

Genetics of ALS progression

Jun 01, 2008

An upcoming paper in the June 1 issue of G&D, from Drs. Hidenori Ichijo and Hideki Nishitoh (University of Tokyo) and colleagues, lends new and valuable insight into the genetics of ALS.

Researchers identify protein associated with sporadic ALS

Oct 18, 2010

Researchers at the University of Massachusetts Medical School have uncovered new evidence suggesting that the SOD1 gene, which is implicated in 20 percent of inherited cases of amyotrophic lateral sclerosis (ALS, or Lou Gehrig's ...

International ALS gene search begins

May 16, 2006

U.S. scientists are leading the first international gene search for typical ALS -- amyotrophic lateral sclerosis, also known as Lou Gehrig's disease.

Recommended for you

Study on pesticides in lab rat feed causes a stir

Jul 02, 2015

French scientists published evidence Thursday of pesticide contamination of lab rat feed which they said discredited historic toxicity studies, though commentators questioned the analysis.

International consortium to study plant fertility evolution

Jul 02, 2015

Mark Johnson, associate professor of biology, has joined a consortium of seven other researchers in four European countries to develop the fullest understanding yet of how fertilization evolved in flowering plants. The research, ...

Making the biofuels process safer for microbes

Jul 02, 2015

A team of investigators at the University of Wisconsin-Madison and Michigan State University have created a process for making the work environment less toxic—literally—for the organisms that do the heavy ...

Why GM food is so hard to sell to a wary public

Jul 02, 2015

Whether commanding the attention of rock star Neil Young or apparently being supported by the former head of Greenpeace, genetically modified food is almost always in the news – and often in a negative ...

The hidden treasure in RNA-seq

Jul 01, 2015

Michael Stadler and his team at the Friedrich Miescher institute for Biomedical Research (FMI) have developed a novel computational approach to analyze RNA-seq data. By comparing intronic and exonic RNA reads, ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.