New research, published in open access journal BMC Immunology, reveals that a prospective treatment for autoimmune diseases such as diabetes and multiple sclerosis can result in serious side effects in mice. The researchers from Stanford University found that 86% of the diabetic mice they treated with peptide immunotherapy died as a result.
In humans type 1 diabetes is a serious autoimmune disease caused by the destruction of insulin producing cells in the pancreas by the body's immune system. This leaves diabetics unable to regulate their blood sugar without injections of insulin and at greater risk of developing blindness, heart disease and nerve problems.
In an effort to treat type 1 diabetes small molecules, known as peptides, are being developed to mimic the cells that trigger the autoimmune response. The idea of this immunotherapy is to trick the body into tolerating the cells that it would otherwise attack by "training" the immune system to ignore the insulin producing cells instead of killing them.
Earlier work had shown peptides derived from a protein known as GAD 65, that is expressed in the insulin producing cells in the pancreas, could be used to reduce the incidence of diabetes in mice that are genetically programmed to develop diabetes (NOD mice). This approach was thought to work by inducing a form of "tolerance" and/or by inducing a type of immune response that can be associated with allergic reactions.
Rosetta Pedotti and Maija Sanna and their colleagues from Stanford University investigated whether the injection of relatively large amounts of GAD 65 peptides into NOD mice might be effective in inducing tolerance and whether it caused any side effects.
The researchers injected the GAD 65 peptides into the abdomen of NOD mice each week for 3 weeks. Unfortunately, the potential therapeutic benefits of this treatment could not be evaluated because of an unanticipated side effect of the treatment. When the researchers gave the mice one further injection with the GAD 65 peptide preparation, four weeks after the original 3 week course of treatment, all of these mice developed a severe allergic reaction causing 86% of them to die within 30 minutes. In contrast, mice that had not received any previous peptide injections showed no adverse reactions.
Peptide immunotherapies are currently being studied in Phase I and Phase II clinical trials for both type 1 diabetes and multiple sclerosis. In contrast to the devastating side effects seen in mice, only minor allergic reactions were observed in clinical trials on over 200 patients and these were limited to around 10 % of patients. The frequency of minor reactions is similar to that seen with approved peptide based drugs like Copaxone. These results have been published in peer-reviewed journals [for example, Kappos et al, Nature Medicine, Oct. 2000].
Peptide immunotherapy has the potential to improve the lives of people at risk from developing asthma or autoimmune diseases – from patients with type 1 diabetes to multiple sclerosis sufferers. But the safety of the treatment must be paramount. Pedotti, Sanna and colleagues recognise the potential of this therapy but stress that 'great care must be taken' when attempting to suppress any autoimmune diseases using peptide immunotherapy. These conclusions are strengthened by earlier work from the same researchers using mice that were induced to have symptoms of another autoimmune disease, an animal model of multiple sclerosis.
This article in freely available in the open access, peer reviewed journal, BMC Immunology (http://www.biomedcentral.com/bmcimmunol/)