Some exciting news recently came from the biotech world, where TOL-3021 passed phase II trials for safety and effectiveness as a possible future treatment for type 1 diabetes. TOL-3021, known as a reverse vaccine, was able to help reduce beta cell destruction by halting the onslaught of the body’s own rogue immune system components.
See more coverage of TOL-3021, and Joslin’s Dr. George King’s response, here
Type 1 diabetes is caused by a renegade immune response in which killer T cells (defending white blood cells involved in the immune response) inappropriately sense the beta cells of the pancreas as foreign and attack them. (The beta cells produce and secrete insulin.) The almost complete death of the beta cells requires those with type 1 diabetes to compensate by injecting insulin every day for the rest of their lives. Although insulin is effective in reducing elevated blood glucose levels, people with type 1 need to make a variety of lifestyle modifications to prevent complications. Until now efforts at slowing or reversing the immune attack have been disappointing.
Most vaccines work by bolstering the immune system so it is better able to fight off attacking infectious bacterial or viral invaders. In autoimmune diseases, the invaders are self-generated. Reverse vaccines have the opposite aim, to suppress selective components of the immune system that have gone haywire, while not interfering with overall immune function.
As part of the trial, Stanford University researchers gave 80 patients with type 1 diabetes TOL-3021 in four different doses once per week over a 12-week period. The trial was randomized, placebo-controlled and patients were blinded to their treatment. TOL-3021 contains a DNA plasmid that codes for proinsulin. A plasmid is a small section of DNA that is capable of autonomous replication outside of the chromosome. Proinsulin is a precursor of insulin that is cleaved enzymatically into C-peptide and insulin before being secreted by the beta cells. Lack of adequate C-peptide in the circulation is an indication of beta cell failure.
All doses of the drug improved the amount of C-peptide secreted by the pancreas as compared to placebo. The rise in C-peptide was accompanied by a decline in the number of attacking T-cells targeting the beta cells. Other immune system constituents were not affected. Overall, patients tolerated TOL-3021 well without serious complications.
The vaccine is light years away from prime time for patients. TOL-3021 still has to undergo Phase III trials which involve a substantially larger patient pool . Often complications that did not arise in Phase II due to the small population size of the trials are unveiled in Phase III of drug testing. In addition, even at this stage there were problems with the staying power of the vaccine. After stopping the vaccine, the amount of C-peptide declined and T-cells levels rose, indicating that its effects wore off with time.
This study was published in the journal of Science Translational Medicine in June 2013.