Toxins, Vol. 17, Pages 282: INM004: Polyclonal Neutralizing Antibodies Against Shiga Toxin as a Treatment for Hemolytic Uremic Syndrome

Toxins doi: 10.3390/toxins17060282

Authors:
Marta Rivas
Mariana Pichel
Vanesa Zylberman
Mariana Colonna
Marina Valerio
Carolina Massa
Romina Pardo
Andrés E. Ciocchini
Santiago Sanguineti
Ian Roubicek
Linus Spatz
Fernando Alberto Goldbaum

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury (AKI). Shiga toxin (Stx)-producing Escherichia coli-associated HUS (STEC-HUS) is one of the leading causes of AKI in children. Approximately 1.5 to 3% of children die during the acute phase, and about 30% experience long-term renal sequelae. Argentina has the highest incidence of STEC-HUS globally. Given the prominent role of Stx in its pathophysiology, STEC-HUS is considered more of a toxemia than a bacterial disease. Stx transport occurs before and after the STEC-HUS onset, allowing for the distinction between an early toxemia phase and an advanced toxemia phase. In this review, we present our efforts to develop INM004, an anti-Stx treatment aimed at ameliorating or preventing the clinical consequences of STEC-HUS. We describe the protein engineering that facilitated this development and the clinical path to demonstrate the safety and efficacy of INM004. This immunotherapy could represent a new step in the treatment of STEC-HUS, which could potentially prevent long-term damage. If phase 3 trials are successful, earlier and broader use of INM004 is envisioned. We also discuss the potential impact of INM004 therapy, targeted vaccination strategies, and new diagnostic tools for this disease.

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Marta Rivas www.mdpi.com