R&D Goals


 

Given the status of atherosclerosis and rheumatoid arthritis as the leading representatives of age dependent diseases, the impact of TOLERAGE for basic pathogenic knowledge and timely treatment of patients is significant.
 
 



The location of an auto immune region of heat shock protein 60 which is recognised by antibodies of the immune system is shown on a 3-D image of the entire protein. It is this attack of the immune system on the bodies own tissues that leads to auto immune diseases such as rheumatoid arthritis,  and  as shown by members of the consortium, atherosclerosis.

 


>> Source Hannes Perschinka et al. Atherosclerosis
 
 
The main performance and research indicators of TOLERAGE will be
 
  • Insights into the role of aging on the immune system, and the induction of tolerance in particular
  • Successful tolerance to heat shock protein 60 in experimental animals
  • Extension of the data obtained in the point above to the successful prevention and treatment of atherosclerosis and rheumatoid arthritis in animals
  • Elucidation of the underlying cellular and molecular mechanisms of tolerance induction
  • Providing a solid experimental and visionary basis for the later translation of the results into the human system, a process beyond the scope of TOLERAGE
     

The clinically relevant outcome of this project is a significant advancement in the knowledge of how and when to induce tolerance to the auto-antigens responsible for age-relevant disease.

 

The human body uses a trick to avoid immune reactions against ingested or inhaled proteins by breaking these down into small fragments, and even single amino acids, that are not recognized as foreign by the immune system, i.e. the immune system becomes tolerant against them (=immunotolerance). This mechanism is especially important in those instances where microbial and human proteins display a high degree of chemical and structural similarity, such as in the case of heat shock protein 60 (HSP60). This process is termed immunological cross-reactivity. With this in mind, we will induce tolerance to heat shock protein 60 as a prototype microbial-human cross-reactive antigen by application via the intestinal (oral) or respiratory (nasal) tract. This should lead to a reduction of specific immunity via tolerance. In addition, we will also focus on the restoration of tolerance in old mice by means various targeted treatments.