- CRISPR-Cas9 technology is used to correct the genetic
mutation responsible for amyotrophic lateral
- Adeno-associated virus is used to transfer the Cas9
gene into motor neurons, which knocks off the SOD1
gene in mice.
- The life span of ALS affected mice treated with gene
therapy extended by 25% compared to those that had not received the
Amyotrophic lateral sclerosis
(ALS) or Lou Gehrig's disease affected patients may find hope in CRISPR-Cas9
gene editing technology. This gene therapy effectively knocked out the disease
causing mutation in ALS model mice which had the human mutation and expanded
their lifespan by 25 percent, shows a new study from the University of
California, Berkeley. The onset of muscle wasting, a characteristic of the
disease which proves to be fatal was delayed by the therapy. The findings are
published in the journal Science Advances
Lateral Sclerosis (ALS)
is a progressive nervous system disorder that primarily affects motor neurons
where the nerve cells gradually die. It is also called Lou Gehrig's disease,
after the baseball player who was diagnosed with it. It affects adults between
the ages of 40 and 70. While the exact cause of the disease remains unknown,
some cases are inherited. ALS
usually begins muscle twitching weakness in a limb, or slurred speech.
The effect of the disease on motor neurons limits the control one has on the
muscles required to move, speak, eat and even breathe. Premature death of motor
neurons in the brain and spinal cord which are crucial to control muscles cause
the disease symptoms. The disease becomes fatal when the muscles that control
Laboratory mice were genetically engineered to contain
the human gene mutations responsible for ALS. The mice expressed mutated genes
that cause about 20 percent of all inherited forms and 2 percent of all case
of ALS worldwide.
"Being able to rescue motor neurons and motor neuron
control over muscle function, especially the diaphragm, is critically important
to being able to not only save patients, but also maintain their quality of
life," said David Schaffer, a professor of chemical and biomolecular
engineering and director of the Berkeley Stem Cell Center.
‘CRISPR technology when used to treat amyotrophic lateral sclerosis (ALS) had an extended lifespan which was nearly about 25 percent.’
The research team used an adeno-associated virus to specifically seek out only motor neurons in the
spinal cord and deliver the Cas9 gene into the nucleus of these cells. In the nucleus, the gene was translated into the Cas9
protein. The Cas9 protein acts as a pair of molecular scissors that cut and disable the
mutant gene SOD1 (superoxide dismutase 1) responsible for ALS.
In mice treated with the CRISPR, the onset of the disease
was delayed by five weeks. Moreover, treated mice lived about a month longer
than the typical four-month lifespan of mice with ALS.
It was found after death that only the only the motor neurons
that had the Cas9 protein in them
had survived, others had died in the course of disease progression.
"The treatment did not make the ALS mice normal and
it is not yet a cure," Schaffer cautioned. "But based upon what I
think is a really strong proof of concept, CRISPR-Cas9
could be a therapeutic molecule for ALS. When we do additional
optimization of the delivery to get CRISPR-Cas9 into an even higher percentage
of cells, we think we are going to see even better increases in lifespan."
- Amyotrophic lateral sclerosis - (https://www.mayoclinic.org/diseases-conditions/amyotrophic-lateral-sclerosis/symptoms-causes/syc-20354022)