Type I diabetes protective peptide

The first indication that it might be possible to prevent the progression of Type 1 diabetes — the form of the disease in which the immune system destroys insulin–producing ß cells in the pancreas — was signalled this week, with promising results from a small, short-term trial with a peptide from the protein hsp60 expressed in autoimmune disease.In 24 November The Lancet, Itamar Raz and colleagues from the Hadassas-Hebrew University Medical School, Jerusalem and the Weitzmann Institute, Rehovot reported that injections of a small subunit of the hsp60 protein had halted the destruction of the ß cells in newly diagnosed patients. "I want to avoid saying anything that would encourage parents to start ringing to get their children injections," said Hubert Kolb*, a professor at the Diabetes Research Institute, Dusseldorf, Germany, "but the message of this research is encouraging."It is in many ways, he argued, a scientific landmark because it is the first proof of concept of a so-called antigen–specific immunomodulation therapy against an autoimmune disease (a trial conducted by another group administering peptide injections to patients with multiple sclerosis was halted because of allergic reactions).But Kolb — a pioneer in the field who played a key role in establishing Type 1 diabetes as an autoimmune disease — cautions that the work does not yet represent a clinical landmark in the battle against Type 1 diabetes because it was tried on only 35 patients and the results looked only at what happened to these people 10 months after completing treatment. Clinicians would, he said, prefer to see results after 2 to 3 years.The peptide that the researchers developed is derived from a molecule called hsp60 that exists in all cells (usually found in the mitochondria) and which is bound to the outer membrane of distressed cells.They knew that hsp60 plays a part — not yet fully understood — in the immune response and interacts with the T cells that are so critical to the immune systems efforts to destroy pathogens and infected cells. hsp60 is also found on the cell surface in autoimmune disease — for example the insulin-producing ß cells in the pancreas — where it interacts with T-cells with the same destructive consequences as if the cell were infected.Knowing this, Raz et al. wanted to identify specific peptide sequences in hsp60 that, when bound to T cells, would alter their behaviour in a way that would uniquely stop them producing the chemicals that destroy the insulin–producing cells.Once they identified a promising sequence they showed that the peptide halted ß-cell destruction in animal experiments, maintaining their ability to produce insulin.All of this research laid the groundwork for the clinical trial reported in The Lancet. The randomised, double blind trial of 35 patients (four did not complete the trial) showed that in those patients assigned the peptide (n=15), the ß-cell activity fell very little compared with those receiving placebos. The team suggested that the peptide works by stimulating the T2 helper cells to release chemicals that have an anti-inflammatory affect, which consequently counteracts production of the inflammatory chemicals produced by T1 helper cells.Dana Elias, from the Weitzmann Institute and part of the company, Peptor, established to commercialise the science, said that she and colleagues would now conduct trials to establish dose levels and treatment schedules for Type 1 diabetes. They also found the specific areas of hsp60 important in rheumatoid arthritis and plan clinical trials to explore the possibility that antigen-specific immunomodulation will also work against this disease.*Kolb is now a paid consultant to Peptor, but was not at the time of this clinical trial.

Type I diabetes protective peptide

A modified cell surface peptide could herald a breakthrough in the treatment of autoimmune diseases.

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