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REGULATION OF COMPLEMENT SYSTEM USING AUR-1400 and aur-1402

Ethan Waisburg UCD School of Medicine and Medical Science, University College Dublin, Belfield, Dublin 4, Ireland


Article

 

Introduction

Atypical Hemolytic Uremic Syndrome (aHUS) is a disease that is genetically-mediated and primarily affects kidney function.1 This syndrome can be characterized by a reduced level of circulating platelets (thrombocytopenia), the breakdown

of red blood cells (hemolysis), and acute kidney failure.2 It is estimated that aHUS has an incidence
of approximately 2 cases per 1,000,000/year in
the United States.3 The death rate of the disease
is approximately 2-10% at first episode and approximately 50% of patients have relapses.4
For most aHUS patients, specific mutations that
affect the alternative complement pathway are responsible, such as C3, factor H, factor I, factor
B and thrombomodulin.5 The complement system plays a key role in the innate immune system by lysing pathogens and identifying damaged tissue
and is composed of over 40 membrane and plasma- associated proteins. 1 This system should be precisely regulated to prevent healthy tissue from being damaged. Conditions such as atypical Hemolytic Uremic Syndrome arise from the dysregulation of complement. This dysregulation results in an attack on the cells that line blood vessels in the kidneys which results in the formation of clots, inflammation and could eventually lead to end-stage renal disease.2 AUR-1400 and AUR-1402 are derivatives
of aurin tricarboxylic acid (ATA), which is a molecule that blocks the complement cascade by inhibiting
the activity of the alternative C3 convertase as well as the assembly of the membrane attack complex (MAC; C5b-9). These compounds could potentially restore complement control and may be used as a therapeutic for diseases such as aHUS.

Objective

The goal of this study is to determine the complement blocking capacity of the novel ATA derivatives AUR- 1400 and AUR-1402 using an established cell motility assay.

 

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