Treating Dogs with ALS-like Disease May Lead to Advances in New Therapy for Humans

A novel gene-silencing therapy intended for patients with ALS (amyotrophic lateral sclerosis) is being tested as a treatment for dogs with degenerative myelopathy, a paralytic disease similar to ALS. The study is currently underway at Tufts University.

“Giving these pets another one-and-a-half to two years of life would be a major success,” said Dominik Faissler, the veterinary neurologist at Cummings School for Veterinary Medicine at Tufts who is leading the study. “Better yet, we’d be doing something for dogs that at the same time contributes to human medicine.”

Canine degenerative myelopathy causes progressive paralysis in a number of dog breeds, including German shepherds, boxers, corgis, Chesapeake retrievers, Rhodesian ridgebacks and Bernese mountain dogs. Dogs with degenerative myelopathy eventually die from respiratory failure, but are often euthanized due to their poor quality of life.

“In dogs, it turns out there’s a mutation in the SOD1 gene, which normally makes an antioxidant protein that helps protect nerve cells from a variety of cellular stresses and injuries,” Robert H. Brown Jr., a University of Massachusetts Medical School neurologist and a leader in ALS research, said in a press release.

“When this gene gets mutated, it becomes toxic to nerves, killing off the motor neurons in dogs the same way that this genetic mutation does in some people with ALS,” he said.

The drug currently being studied involves a single injection of an engineered adenovirus into the spinal fluid. It is designed to deliver DNA particles across the blood-brain barrier and into the central nervous system (CNS). These DNA particles then “silence” mutated genes which are believed to cause the progressive paralysis observed in dogs suffering from degenerative myelopathy.

This modified adenovirus is from a family of viruses that is commonly implicated in causing the common cold. The virus is naturally able to cross into the CNS, a trait which researchers are exploiting as a vehicle to deliver the therapy to the defective genes associated with canine degenerative myelopathy.

The study, which began in December 2016, currently has four dogs enrolled. The dogs are assessed every three months, at which point they undergo testing of their motor and neurological function.

Initial results from the pilot study indicate that the treatment appears to be safe. However, researchers note that it is too early to determine if the therapy will be effective in reversing disease. The therapy has already demonstrated encouraging results in mice, which were genetically modified to have a condition similar to ALS.

According to Brown, a successful study in dogs could eventually lead to clinical trials in humans. A California-based biotech, Ionis Pharmaceuticals, is currently testing a similar therapy for SOD-1 related ALS as well as for a mutation found in Huntington’s disease. Brown said that such treatments could one day be used for a number of neurodegenerative and neuromuscular diseases.