A new approach to treating disease by interfering with faulty genes may help patients with an incurable nerve-wasting illness called amyotrophic lateral sclerosis, researchers in Britain and Switzerland reported on Sunday.
Tests in mice suggest that RNA interference, while not a cure, can slow the progression of the invariably fatal condition.
ALS, or Lou Gehrig’s disease, is the most common form of motor neuron disease. It is caused when neurons in the spinal cord die, leading to muscle wasting and total paralysis.
About 10 percent of cases are inherited, caused by at least 100 different mutations in a protein known as SOD1. Mice have been genetically engineered to carry this faulty human gene and they develop a disease that looks like human ALS.
Two separate teams of researchers used a gene therapy approach to interfere with the faulty SOD1 gene in mice. Each team showed, independently, that they could delay the disease’s effects and help their gene-engineered mice live longer.
The teams used different lentiviruses -- long-lived viruses related to the AIDS virus that are very good at delivering genetic material to cells.
The viruses were made harmless and then genetically engineered to carry genetic material called RNA that would interfere with the faulty RNA produced by the mutant human SOD1 genes in the mice.
Results showed that using lentiviruses to “silence” the mutant genes provided “considerable therapeutic benefit by delaying onset and prolonging duration of motor neuron disease,” Patrick Aebischer of the Ecole Polytechnique Federale de Lausanne in Switzerland and colleagues wrote in their report, published in the journal Nature Medicine.
Aebischer’s team considered that healthy SOD1 is probably important for something, so they altered their gene therapy approach to also deliver a healthy version of SOD1. Their mice swam and walked better than untreated mice.
In a second study, a team at Britain’s Oxford BioMedica Plc injected their gene therapy into not only the spines but into various muscles of the ALS mutant mice.
When Mimoun Azzouz of Oxford Biomedica and colleagues dissected the mice, they found the treated mice had more healthy motor neurons than untreated mice.
It took twice as long as normal for ALS symptoms to start and the mice lived for 80 percent of their normal lifespan, Azzouz’s team reported in Nature Medicine.
