Splenic modulation of SHP-2 activity as a therapeutic option for systemic lupus erythematosus
Ended Project Grant Awarded Last action
- Award ID
- R21AR081535
- Recipient
-
Masonic Medical Research Lab UEI QEMHDDHERR74
- Awarding agency
-
National Insititue of Arthritis and Musculoskeletal and Skin Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $1,071,026
Award facts
- Assistance listing
- 93.846 Arthritis, Musculoskeletal and Skin Diseases Research
- Completion date
- Originally
- Place of performance
- New York, USA
Award details come from USAspending.gov.
Description
- Abstract
- Systemic lupus erythematosus (SLE) is a multisystem autoimmune disorder characterized by a loss of tolerance to multiple endogenous antigens, for which there is no cure. Current therapeutic options for SLE patients involve a variety of non-specific immunosuppressive or anti-inflammatory agents that have significant associated side effects and are often inadequate. There is thus a great unmet need to develop curative therapies for this disease. In SLE, tissue injury is often mediated by aberrant expression of immunoregulatory signaling proteins. In particular, SRC homology region 2 domain-containing phosphatase-2 (SHP-2) has been shown to enhance disease-active T cell proliferation and promote downstream cytokine production, each of which are innately tied to the pathophysiology of the disease. The importance of this phosphatase in the promotion of SLE has been further demonstrated by its inhibition, wherein systemic treatment normalized many of the symptoms of the disease concomitant with an extension of lifespan. Yet, SHP-2 is expressed throughout the body, thus the potential for off-target effects from systemic therapies is great. The spleen is the largest secondary lymphoid organ and an active regulator of the immune response, with a structure designed to increase the likelihood of rare interactions between cells, in particular cognate lymphocytes and antigen-presenting cells. While the spleen is not considered a target organ in SLE, IT is an active site for autoantibody generation and the accumulation of pathogenic cells, including dntcs, which are trafficked throughout the body to elicit the observed multi-organ damage. We thus hypothesize that the localization of therapeutics to the spleen, in particular modulators of SHP-2, may be sufficient to enable a systemic therapeutic effect. To accomplish this, we propose to utilize engineered senescent red blood cell mimetic nanohybrids to specifically deliver small molecule inhibitors or oligonucleotide-based therapeutics to the splenic milieu. If successful, the generated materials may potentiate the discovery of novel therapeutic options for the treatment of SLE with the capacity for increased specificity and decreased side effects.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $0 | |
| Amendment | $13,706 | |
| Amendment | $176,220 | |
| Amendment | $176,220 | |
| Amendment | $234,960 | |
| Amendment | $234,960 | |
| Original award | $234,960 |
Quick answers
Who received award R21AR081535?
R21AR081535 was awarded to Masonic Medical Research Lab by National Insititue of Arthritis and Musculoskeletal and Skin Diseases (National Institutes of Health) on March 1, 2023.
How much is award R21AR081535 worth?
$1,071,026 has been obligated on R21AR081535.
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