Antisense offers key to new MS treatment

A new way to treat multiple sclerosis (MS) with antisense drugs is being developed by Melbourne company Antisense Therapeutics with the assistance of its US partner Isis Pharmaceuticals.

The company has started pre-clinical toxicology studies for its lead drug ATL1102 after successfully demonstrating activity in an animal model for MS.

CEO Mark Diamond said that Antisense hopes to begin Phase I clinical trials in Australia in early 2003.

MS, which affects between 12,000 and 15,000 Australians and 2.5 million people worldwide, is an autoimmune disease in which recurrent inflammation of nerves in the brain and spinal column leads to destruction of the nerves over time. The immune response seems to be directed at the myelin sheath surrounding the nerve cells.

Most drugs for MS act by reducing the inflammatory response, but while they can slow progression of the disease, they often have serious side effects.

Antisense said it believed its approach offered a new way to treat MS. The company uses specially formulated oligonucleotides to specifically block production of target proteins.

The technology was developed by Isis Pharmaceuticals. Antisense holds an exclusive licence from Isis to develop ATL1102.

ATL1102 acts by preventing production of the VLA-4 receptor on certain immune cells. Overproduction of this receptor has been implicated in the inflammatory response seen in MS.

"Most conventional drugs modify the activity of disease causing proteins in the body," Diamond said. "Our antisense drug would go to work earlier, stopping the body from making the VLA-4 protein that is responsible for MS progression. We hope our antisense drug will provide efficacy, safety, and dosing advantages over other agents being developed for MS."

He explained that the approach used by Antisense and Isis had been validated by the clinical results of a monoclonal antibody against VLA-4 developed by Elan and Biogen, which showed reduced progression of the disease and a decreased rate of relapses.

But according to Diamond, monoclonal antibodies have issues with rejection and neutralisation by the body's immune defences. An antisense approach sidesteps these issues and provides advantages in delivery methods and dosage administration, he said.

"What we are aiming to achieve with our VLA-4 antisense is to demonstrate a significant slowing down in the progression of the disease, so as to offer patients relapse-free, longer periods of remission. That would substantially improve the quality of life for people with MS," Diamond said.

Antisense Therapeutics listed on the ASX in December 2001.