First NW Patient To Receive OHSU/VAMC-Invented Ms Drug
04/02/11 Portland, Ore.
The Montesano, Wash. woman will have infusion of promising RTL1000 this morning.
Anne Foster, who has secondary-progressive MS, will be the third person in the country to receive an infusion of the OHSU/VAMC-invented drug, RTL1000, as part of a Phase I trial when she arrives for treatment at OHSU's Center for Health & Healing this morning at 9. She will be awake as the drug is administered intravenously and will stay in the hospital for 24 hours for evaluation.
"Since I was diagnosed with MS, a lot of things have changed and there are now medications for MS, but there's a whole bunch of people that don't fit into these medications," said Foster, who was told she has MS in 1990, but who has suffered since childhood from what she believes were early signs of the disease.
"I'm excited to have another chance. I'd like to see a new medication that helps people with secondary-progressive MS because we're a group of people that there really isn't anything for. Maybe this'll work."
OHSU and VAMC researchers who developed RTL1000 are equally enthusiastic about the drug's potential. Named for the "recombinant T-cell receptor ligand" (RTL) that is the center of its activity, RTL1000 is a highly selective protein that binds to disease-causing white blood cells, or T-cells, and inactivates them.
"It's fantastic to see our scientists come up with an idea, engineer and make this protein, show that it works in a mouse model, and partner with OHSU's technology transfer office to patent the process and license it to local biotechnology company, which went on to get venture capital to fund this trial," said Dennis Bourdette, M.D., professor and chairman of neurology in the OHSU School of Medicine and director of the Multiple Sclerosis Center of Oregon. "This is one example of the Oregon-based biotechnology spin-offs resulting from research at OHSU/VA."
"I'm very proud of our research group," he added. "This is good for our patients, it's good for OHSU and it's good for Oregon."
MS is caused by a subgroup of "pathogenic" T-cells that attack myelin, the fatty sheath insulating nerve fibers in the brain and spinal cord, and cause the fibers to lose their ability to conduct impulses. RTL1000 was bioengineered to bind specifically to the T-cells believed to cause MS, and then inactivate or "stun" these cells.
Arthur Vandenbark, Ph.D., professor of neurology, and molecular microbiology and immunology, OHSU School of Medicine, and senior research career scientist at the VAMC, led the RTL1000 research team that included Halina Offner, Ph.D., professor of neurology, and anesthesiology and peri-operative medicine at OHSU and the VAMC, and Gregory Burrows, Ph.D., OHSU research associate professor of neurology.
Vandenbark called the clinical trial with RTL1000 "the holy grail" of his research. The drug has the "exquisite specificity" for disease causing T-cells that he has long sought.
"Nearly all the therapies out there now are relatively non-specific. They block too many of the T-cells, and some are needed to protect against viruses in the central nervous system," Vandenbark said. "Our idea was to develop something that's really, really selective."
In early studies that Vandenbark, Offner and Burrows conducted on mouse models for MS, RTL1000 appeared to reverse demyelination and nerve fiber damage. That meant the drug was both neuroregenerative and neuroprotective.
"In our mouse model, we tested whether we could wait until paralysis and loss of myelin and damage to fibers before starting treatment with RTL1000. We were amazed to find out that RTL1000 could reverse the damage that had already happened. The results were unbelievable," Vandenbark said. "We actually had recovery of both the myelin and axons (nerve fibers). We interpret that to mean the damage probably wasn't complete, and if we catch it early enough, we can prevent the disease from becoming irreversible."
RTL1000's appearance in a clinical trial is the culmination of more than 20 years of work by MS scientists and clinicians at OHSU and the VAMC to develop a treatment that enhances the body's natural ability to control disease-causing T-cells. They recently helped launched an international trial for another MS drug invented by Vandenbark and Offner, called NeuroVax, that boosts the activity of protective T-cells that regulate MS. This treatment approach, referred to as T-cell receptor peptide vaccination, may also prove useful for treating a variety of autoimmune diseases, such as diabetes mellitus and rheumatoid arthritis.
"There are very few academic research programs focused on MS in the country that have invented two therapies that have gone on to clinical trials," Bourdette said. "That is unusual. We're talking about complete invention, from concept, designing and making a prototype therapy, to testing it and helping move it into clinical trial."
During the Phase I trial on RTL1000, initiated by Tigard-based Artielle ImmunoTherapeutics Inc., researchers will test the drug in a total of 30 participants at six study sites, including OHSU, Yale University, Indiana University, University of Kansas Medical Center, University of Maryland, and the MS Center at Evergreen, Kirkland, Wash. They will evaluate its safety, determine a safe dosage range and identify side effects.
According to the National MS Society, MS affects an estimated 400,000 Americans, and 200 people are diagnosed each week. About 2.5 million people worldwide are believed to have MS.
OHSU and Drs. Vandenbark, Offner and Burrows have a significant financial interest in Artielle ImmunoTherapeutics, Inc. This potential conflict was reviewed, and a management plan approved by the OHSU Conflict of Interest in Research Committee and the Integrity Program Oversight Council was implemented.