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Desarrollo de un producto anti-toxina shiga para la prevención del síndrome urémico hemolítico / Development of a product anti-Shiga toxin for prevention of the hemolytic uremic syndrome
Hiriart, Yanina; Pardo, Romina; Bukata, Lucas; Lauché, Constanza; Muñoz, Luciana; Goldbaum, Fernando; Sanguineti, Santiago; Zylberman, Vanesa.
Affiliation
  • Hiriart, Yanina; Inmunova S.A. Buenos Aires. AR
  • Pardo, Romina; Inmunova S.A. Buenos Aires. AR
  • Bukata, Lucas; Inmunova S.A. Buenos Aires. AR
  • Lauché, Constanza; Inmunova S.A. Buenos Aires. AR
  • Muñoz, Luciana; Inmunova S.A. Buenos Aires. AR
  • Goldbaum, Fernando; Inmunova S.A. Buenos Aires. AR
  • Sanguineti, Santiago; Inmunova S.A. Buenos Aires. AR
  • Zylberman, Vanesa; Inmunova S.A. Buenos Aires. AR
Medicina (B.Aires) ; 78(2): 107-112, abr. 2018. ilus
Article in Spanish | LILACS | ID: biblio-954958
Responsible library: BR1.1
RESUMEN
El síndrome urémico hemolítico (SUH) típico es una enfermedad huérfana causada por cepas de Escherichia coli productoras de toxina Shiga (Stx) y caracterizada por daño renal agudo, anemia hemolítica microangiopática y plaquetopenia. Es endémico en Argentina, el país con mayor incidencia de SUH en el mundo. Debido al rol fundamental de la Stx en su patogenia, se puede considerar que, como otras toxemias conocidas, el SUH podría ser tratado con anticuerpos. Este trabajo describe el desarrollo de un nuevo tratamiento capaz de neutralizar el efecto tóxico de distintas variantes de la Stx. El tratamiento consiste en fragmentos F(ab')2 provenientes de un antisuero equino cuya eficacia y potencia contra Stx1 y Stx2 se comprobó en diferentes modelos preclínicos. El producto mostró ser seguro en animales, presentó la farmacocinética descripta para compuestos similares y se pudo establecer una posible ventana terapéutica para su adecuada administración. En conjunto, los resultados preclínicos obtenidos validan la realización de un estudio clínico de primer uso en humanos. En dicho estudio, que se realizará en el Hospital Italiano de Buenos Aires, se analizará la seguridad y la farmacocinética del producto en voluntarios adultos sanos. Estos resultados sentarán las bases para la realización del estudio clínico fase II en pacientes pediátricos con infección por cepas de E. coli productoras de Stx.
ABSTRACT
The typical hemolytic uremic syndrome (HUS) is an orphan disease caused by Shiga toxin(Stx) -producing Escherichia coli strains and characterized by acute kidney damage, microangiopathic hemolytic anemia and low platelet count. It is endemic in Argentina, the country with the highest incidence of HUS in the world. Stx is essential for its development and therefore, HUS is considered a toxemic non-bacteremic disorder, which could be treated with antibodies. Herein we describe the development of a new treatment capable of neutralizing the toxic effect of Stx and its variants. The treatment consists of F(ab')2 fragments from an equine antiserum whose efficacy and potency against Stx1 and Stx2 were proved in different preclinical models. The product was shown to be safe in animals. Furthermore, the anti-Stx F(ab')2 pharmacokinetic was shown to be similar to that of analogous compounds and a therapeutic window for its administration was determined. Altogether, these preclinical results warrant testing in humans. The phase I clinical trial will be performed at the Hospital Italiano in Buenos Aires to evaluate the safety and pharmacokinetics of the product in healthy adult volunteers. Based on the results of this study, a phase II clinical trial will be planned in pediatric patients diagnosed with infection by Stx-producing E. coli strains.
Subject(s)

Full text: Available Collection: International databases Health context: Sustainable Health Agenda for the Americas / SDG3 - Health and Well-Being / Neglected Diseases Health problem: Goal 9: Noncommunicable diseases and mental health / Target 3.3: End transmission of communicable diseases / Neglected Diseases / Zoonoses Database: LILACS Main subject: Immunoglobulin Fab Fragments / Drugs, Investigational / Shiga Toxin 1 / Shiga Toxin 2 / Escherichia coli Infections / Hemolytic-Uremic Syndrome Type of study: Controlled clinical trial Limits: Humans Country/Region as subject: South America / Argentina Language: Spanish Journal: Medicina (B.Aires) Journal subject: Medicine Year: 2018 Document type: Article Affiliation country: Argentina Institution/Affiliation country: Inmunova S.A/AR
Full text: Available Collection: International databases Health context: Sustainable Health Agenda for the Americas / SDG3 - Health and Well-Being / Neglected Diseases Health problem: Goal 9: Noncommunicable diseases and mental health / Target 3.3: End transmission of communicable diseases / Neglected Diseases / Zoonoses Database: LILACS Main subject: Immunoglobulin Fab Fragments / Drugs, Investigational / Shiga Toxin 1 / Shiga Toxin 2 / Escherichia coli Infections / Hemolytic-Uremic Syndrome Type of study: Controlled clinical trial Limits: Humans Country/Region as subject: South America / Argentina Language: Spanish Journal: Medicina (B.Aires) Journal subject: Medicine Year: 2018 Document type: Article Affiliation country: Argentina Institution/Affiliation country: Inmunova S.A/AR
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