Novel approaches for the treatment of autoimmune disease
Ended Project Grant Awarded Last action
- Award ID
- R43AI174502
- Recipient
-
Astero Erado Inc. UEI Z3JWEMNYNRT9
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $825,639
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date
- Originally
- Place of performance
- Houston, TX 77021, USA
Award details come from USAspending.gov.
Description
- Abstract
- The overall goal of this project is to develop a novel therapeutic for the treatment of immune- mediated thrombotic thrombocytopenic purpura (ittp). Ittp is an acute, life-threatening disease that without treatment, leads to a >90% mortality rate. IT is caused by deficiency of a disintegrin and metalloprotease thrombospondin type 1 motif, member 13 (ADAMTS13), which is a protease that cleaves ultra large aggregates of VON willebrand factor (VWF). Such aggregates of VWF bind to platelets, resulting in blood clots. Consequently, ADAMTS13 deficiency leads to microthrombus formation in arterioles and capillaries, and ittp is characterized by hemolytic anemia, thrombocytopenia and organ damage, with possible severe cardiac, renal, neurological and gastrointestinal effects. For ittp, ADAMTS13 deficiency is caused by autoantibodies specific for this protease. Current treatments are therefore directed towards reducing the levels of these antibodies by plasma exchange and the use of general immunosuppressants (corticosteroids, rituximab). In addition, a bivalent nanobody (caplacizumab) that inhibits VWF-platelet interactions has recently been approved to treat ittp. Despite treatment, however, relapses occur in 30-50% ittp patients. Further, the treatments can have adverse effects such as abnormal bleeding (caplacizumab) and/or increased risk of infection due to general immunosuppression. Rituximab also has a slow onset of action and is used in combination with plasma exchange. Consequently, there is a need to develop therapies for ittp that have rapid effects and high specificity for the causal agent of disease, namely the autoantibodies. This application seeks to address the need for new and improved therapies for ittp by generating engineered, antibody-based reagents that specifically and rapidly deplete ADAMTS13-specific antibodies. Importantly, these depleting agents are highly selective and do not have general immunosuppressive effects. This first-in-class, novel technology has been named seldeg technology (for selective degradation). The specific aims of the study are: 1. To design and express seldegs to target ADAMTS13-specific antibodies. 2. To analyze the stability and binding activity of the seldegs. The proposed approach could be transformative for the management of ittp, and also has relevance to the use of seldeg-based strategies for multiple other clinical settings where pathogenic antibodies cause disease.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $0 | |
| Amendment | $275,213 | |
| Amendment | $275,213 | |
| Original award | $275,213 |
Quick answers
Who received award R43AI174502?
R43AI174502 was awarded to Astero Erado Inc. by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on January 1, 2023.
How much is award R43AI174502 worth?
$825,639 has been obligated on R43AI174502.
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