Gene therapy can help mice with an ALS-like condition Deco Images II / Alamy

A new delivery method could take us a step closer to a gene therapy for amyotrophic lateral sclerosis (ALS), a neurodegenerative disorder in which nerve cells progressively stop working throughout the spinal cord and the brain.

Animal studies have already suggested that ALS can be prevented by replacing the mutated genes that cause some forms of the condition with normal versions. But delivering genes to nerve cells in the spine is a challenge.

The new method involves injecting corrected genes beneath the tissues that protect the spinal cord. The technique has been shown to correct 89 per cent of genes associated with an inherited form of ALS.


Ten per cent of ALS patients have an inherited version of the disease, and 20 per cent of those people have a mutation in a gene called SOD1 that causes their ALS. There is currently no effective treatment for this familial form of ALS or the more common sporadic ALS, both of which have a median survival of 3 to 5 years after the onset of symptoms.

No barrier

Martin Marsala and Mariana Bravo Hernandez at the University of California San Diego and their colleagues inserted a compound that silences the SOD1 gene into a virus. They then injected the virus into adult mice with an inherited ALS-like condition just above their spinal cords. “We’re injecting it beneath the membranes that protect the spinal cord, so there’s no barrier. That’s what allows us to impact all the neurons inside the spinal cord,” says Bravo Hernandez.

In the treated mice, the onset of ALS symptoms was delayed by 80 days, and they never reached the levels of muscle stiffness seen in untreated mice, who ended up unable to turn over, drink or eat.

The treated mice ran around as much as mice without the disease even after 13 months, and they retained strength in their limbs. “There are long-term effects,” says Bravo Hernandez.

The treated mice’s muscles were still receiving electric signals from the brain, suggesting that their neurons were intact, she says. She presented her work this week at the Society for Neuroscience annual meeting in San Diego.

No gaps

At the end of the trial, the team examined the muscle tissue of the animals. In the untreated mice, they saw large gaps in motor neurons. But in the treated animals, neurons spread through their spinal column as in healthy mice. Bravo Hernandez says the lack of neurons in untreated mice was due to widespread misfolded proteins. In the treated mice, these misfolded proteins were reduced by 50 per cent in the upper spine and 80 per cent in the lower spine.

The team has shown that this injection directly above the spinal cord can affect neurons throughout the spinal column in non-human primates, as well, and they are planning to do further trials of this gene therapy in primates.

If they go well and ultimately lead to a therapy for humans, it could lead to more people using genetic screening to find out if their family is genetically at risk for this form of ALS, and then potentially treating the disease before symptoms begin.

“As long as you don’t have a treatment, maybe some families would opt out and rather not know. But once you know that you could potentially get treated, you’re probably going to change that attitude,” said Kathrin Meyer of the Nationwide Children’s Hospital in Ohio at a press conference.