# Autoantibody depletion for the therapy of autoimmune disease

> **NIH NIH R43** · ASTERO ERADO INC · 2021 · $246,229

## Abstract

PROJECT SUMMARY/ABSTRACT
The overall goal of this project is to develop a novel therapeutic for the treatment of autoimmune
atypical hemolytic uremic syndrome (aHUS). Autoimmune aHUS is a rare, life-threatening
disease that affects both children and adults. It is caused by autoantibodies that recognize the
negative regulator of the alternative complement pathway, factor H (FH). FH-specific antibodies
both block FH activity and result in FH depletion. The dysregulated complement activation that
ensues results in microangiopathic hemolytic anemia, thrombocytopenia and acute kidney
damage that can culminate in renal failure.
 Although there are currently several therapies for autoimmune aHUS, all of these lead to
general immunosuppression and other severe side effects. For example, plasma exchange
results in adverse consequences in a high percentage of patients. The more recently developed
use of antibodies such as eculizumab that are specific for complement component C5 has
beneficlal therapeutic effects. However, C5 blockade also substantially increases the risk of
infection by pathogens that include meningococci and pneumococci. In addition, the underlying
cause of disease, namely the levels of FH-specific antibodies are not affected by complement
blockade. The risk of recurrence following discontinuation of C5-targeted therapy is therefore
high, and such recurrence is usually severe and rapid.
 As a result of the limitations of existing therapies for autoimmune aHUS, there is a need for
the development of therapeutics that target the pathogenic antibodies. This application seeks to
address this need by generating engineered, antibody-based reagents that specifically and rapidly
deplete FH-specific antibodies, whilst not affecting the levels of antibodies that have a protective
role against infection etc. This first-in-class, novel technology is called Seldeg technology (for
selective degradation).
 The Specific aims of the study are:
 1. To design and express Seldegs to target FH-specific antibodies.
 2. To analyze the stability and binding activity of the Seldegs.
 This approach could not only be transformative for the management of this potentially
devastating disease, but would also lay the foundations for analogous approaches to be taken in
many other clinical settings where pathogenic antibodies lead to disease.

## Key facts

- **NIH application ID:** 10138869
- **Project number:** 1R43AI157024-01
- **Recipient organization:** ASTERO ERADO INC
- **Principal Investigator:** Sunil Kannanganat Sidharthan
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $246,229
- **Award type:** 1
- **Project period:** 2021-08-23 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10138869

## Citation

> US National Institutes of Health, RePORTER application 10138869, Autoantibody depletion for the therapy of autoimmune disease (1R43AI157024-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10138869. Licensed CC0.

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