Lab chat: Genetic clues to Lou Gehrig’s disease
Hunting for genetic clues to neurodegenerative diseases such as amyotrophic lateral sclerosis (better known as ALS, or Lou Gehrig’s disease) and spinal muscular atrophy (SMA), scientists at the Salk Institute in California have zeroed in on a tiny molecule, microRNA 218. The team used the CRISPR gene editing tool to produce mice without that molecule — and what they found could improve understanding of the diseases. I chatted with lead investigator Samuel Pfaff about his work, published in the journal Science.
What happens to mice that don’t have microRNA 218?
Right after they’re born, they die. They die because they can’t breathe. They can’t move. They can’t eat. It’s basically the most extreme form of paralysis you can envision.
What was going on?
[Their motor neurons] were unable to form good synaptic connections with muscles. It’s sort of like having the cord to your lamp on the floor, close to the electrical outlet, but not plugged in: The lamp isn’t going to turn on…. Also, the the motor neurons began to die. These are all the hallmarks, the signature features, of ALS and SMA.
What’s the next step for your research?
We have shown that the loss of the microRNA looks a lot like a motor disease. [Now we need to] show that the motor diseases have an effect on the microRNA. We have begun looking at gene activity levels in patients with ALS and SMA, to see if there’s a link.
What kind of drug therapies could come out of your work?
The idea would be to infuse a patient with something that is structurally similar to microRNA 218. Think of it as a supplement …That’s only a speculative idea. But it’s not implausible, if the microRNA turns out to be directly relevant to motor diseases.