Rivka Abulafia-Lapid, PhD and Henri Atlan MD, PhD, Human Biology Research Center, Hadassah University Hospital and Irun R. Cohen, MD, The Weizmann Institute of Science.
Background
Several studies have suggested that HSP70 and HSP90 may have a role in the pathogenesis of autoimmune disorders. In addition, T-cell responses to other HSPs have also been suggested in diabetes. The present invention relates to HSP70 peptides and their use in the diagnosis and treatment of autoimmune diseases, primarily type I diabetes, as well as SLE, multiple sclerosis and rheumatoid arthritis. More specifically, the outcomes from studies based on this technology represent a step forward in the development of effective immunomodulation therapy of type I diabetes in children.
The immunization with HSP70 peptides for therapy and the use of HSP70 antibodies as new disease marker are novel avenues towards the goal of type I diabetes eradication.
Market
Type I diabetes is a serious disease that affects an estimated 1 million Americans. Annually, there are 79,800 new cases in the U.S. alone, and 123,000 children in the U.S. under the age of 20 have Type 1 diabetes. It is estimated that the direct medical costs in the U.S. is $44 billion per year.
The Innovation
The novel HSP70 peptide approach used in this project takes advantage of natural processes in the body in order to manipulate the immune system. Our research has shown that type 1 pediatric diabetic patients, compared to controls, manifested heightened T-cell proliferative responses to HSP70 and HSP60, but not to HSP90. This finding adds HSP70 to the list of proteins involved in the autoimmune process in type I diabetes. The involvement of Tcell proliferation to HSP60 and HSP70 in disease may be the realization of an autoimmune potential naturally present in the general population.
R&D Program
We have shown that administering an HSP60 peptide to mice could arrest diabetes progression associated with the down-regulation of autoimmunity to other auto-antigens targeted in type I diabetes, such as GAD and insulin. Recently, a clinical trial of therapeutic vaccination with p277, an HSP60 peptide, has shown effectiveness in arresting cell destruction in adults. However, it was unsuccessful in treating type I diabetes in children. Taking into account that the HSP70 molecule appears to have a role in antigen presentation and autoantibodies against HSP70 have been found in patients suffering from autoimmune diseases such as SLE and multiple sclerosis, an additional investigation was carried out with HSP70 which revealed very interesting results in the involvement of type I diabetes.
Children with newly diagnosed type I diabetes manifested heightened T cell autoimmunity to HSP70 and to HSP60, but not to HSP90, as well as elevated levels of antibodies to HSP70 and to HSP60. The promising results obtained with HSP70 warrants future studies for the use of HSP70 peptides as a therapeutic vaccine in children with type I diabetes.
We have validated the role of the peptides in NOD mice model. While the control groups showed 50% incidence of spontaneous diabetes emerging at approx. 13 weeks of age, significant change was observed with three of our leading peptides. These groups showed 0-10% diabetes which was delayed in the peptide treated groups to week 19.
The subsequent R&D program will be based on the following:
- Continue validating the role of the peptides in an animal model (NOD mice) including immunological, pre-clinical toxicity and efficacy studies
- Develop an “anti-HSP70 auto-antibodies identification kit” in combination with other auto-antibodies, for early Type 1 Diabetes diagnosis
- Test HSP70's peptide derivates as therapeutic substances in animal models for other autoimmune diseases including SLE, MS and RA
- Perform Phase I clinical trial in children using the two major peptides, p27 and p35
Contact
Yuval Kupitz,
Business Development, Pharmaceuticals
Tel: +972-2-6778364
Email: yuvalk@hadasit.co.il
