Menu

CRISPR Proves Promising for Treating ALS in Mice

The gene-editing tool was effective in disabling a defective gene responsible for some forms of amyotrophic lateral sclerosis. 

Dec 21, 2017
Katarina Zimmer

CHRIS BICKEL, AAAS CRISPR-Cas9 gene editing can extend survival in a mouse model of amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, according to a study published yesterday (December 20) in Science Advances.

“The treatment did not make the ALS mice normal and it is not yet a cure,” study coauthor David Schaffer, a professor of chemical and biomolecular engineering at the University of California, Berkeley, says in a press release. “But based upon what I think is a really strong proof of concept, CRISPR-Cas9 could be a therapeutic molecule for ALS.”

ALS, or Lou Gehrig’s disease, affects some 20,000 Americans and is characterized by the premature death of motor neurons in the brain stem and spinal cord. The disease causes progressive muscle deterioration and eventually results in paralysis and death. There are no available treatments to delay the muscle wasting and currently approved drugs can extend survival by a few months at most.

Schaffer and his colleagues suspected that ALS could be treated through genome editing because some forms of the disease (around 20 percent of inherited forms and 2 percent of all cases) are caused by dominant mutations in a gene that encodes superoxide dismutase 1 (SOD1), an enzyme that helps protect cells against toxic free radicals.

The scientists delivered a gene encoding a Cas9 protein designed to excise the SOD1 gene into a mouse model of ALS along with a viral vector capable of penetrating the spinal cord to access the nuclei of affected motor neurons.

Compared with untreated mice, the treated rodents experienced an overall improvement to their condition—a 37 percent delay in disease onset and a 25 percent increase in survival. They lived about one month longer than the untreated animals, which had a lifespan of around four months.

This treatment is only relevant to a very rare form of ALS and more work is needed to determine its effectiveness, Eric Topol, a geneticist at Scripps Research Institute who was not involved in the study, tells Gizmodo. However, he adds, “the results were nonetheless encouraging with many positive neurologic signs and delayed onset.”

Schaffer’s current goal is to design a highly modified adeno-associated virus, or AAV, that not only targets motor neurons, but other cells that appear to harm them. “I tend to be really cautious, but in this case, I would be quite optimistic that if we are able to eliminate SOD1 within not just the neurons but also the astrocytes and supporting glia, I think we are going to see really long extensions of lifespan,” he says in the press release.

Modified AAVs have been employed as delivery vehicles for gene therapy against other diseases, including a rare form of genetic blindness (which was approved for use in humans by the US Food and Drug Administration this week), as well as mouse models of Duchenne muscular dystrophy and Huntington’s disease.

“Taken together with the recent, very promising initial gene therapy results for patients with Huntington’s Disease, we’re seeing some new therapeutic doors to some of the most serious nervous systems diseases,” Topol tells Gizmodo

January 2019

Cannabis on Board

Research suggests ill effects of cannabinoids in the womb

Marketplace

Sponsored Product Updates

FORMULATRIX® digital PCR technology to be acquired by QIAGEN
FORMULATRIX® digital PCR technology to be acquired by QIAGEN
FORMULATRIX has announced that their digital PCR assets, including the CONSTELLATION® series of instruments, is being acquired by QIAGEN N.V. (NYSE: QGEN, Frankfurt Stock Exchange: QIA) for up to $260 million ($125 million upfront payment and $135 million of milestones).  QIAGEN has announced plans for a global launch in 2020 of a new series of digital PCR platforms that utilize the advanced dPCR technology developed by FORMULATRIX combined with QIAGEN’s expertise in assay development and automation.
Application of CRISPR/Cas to the Generation of Genetically Engineered Mice
Application of CRISPR/Cas to the Generation of Genetically Engineered Mice
With this application note from Taconic, learn about the power that the CRISPR/Cas system has to revolutionize the field of custom mouse model generation!
Translational Models of Obesity, Dysmetabolism, Diabetes, and Complications
Translational Models of Obesity, Dysmetabolism, Diabetes, and Complications
This webinar, from Crown Bioscience, presents a unique continuum of translational dysmetabolic platforms that more closely mimic human disease. Learn about using next-generation rodent and spontaneously diabetic non-human primate models to accurately model human-relevant disease progression and complications related to obesity and diabetes here!
BiochemAR: an augmented reality app for easy visualization of virtual 3D molecular models
BiochemAR: an augmented reality app for easy visualization of virtual 3D molecular models
Have you played Pokemon Go? Then you've used Augmented Reality (AR) technology! AR technology holds substantial promise and potential for providing a low-cost, easy to use digital platform for the manipulation of virtual 3D objects, including 3D models of biological macromolecules.