The decedent model: A new paradigm for de-risking high stakes clinical trials like xenotransplantation.
Am J Transplant
; 24(4): 526-532, 2024 Apr.
Article
en En
| MEDLINE
| ID: mdl-38341026
ABSTRACT
The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. These results prompt us to question how faithfully data from the NHP model translate into human outcomes. Before attempting any further heart xenotransplants in living humans, it is highly advisable to gain a more comprehensive understanding of why the promising preclinical NHP data did not accurately predict outcomes in humans. It is also unlikely that additional NHP data will provide more information that would de-risk a xenoheart clinical trial because these cases were based on the best practices from the most successful NHP results to date. Although imperfect, the decedent model offers a complementary avenue to determine appropriate treatment regimens to control the human immune response to xenografts and better understand the biologic differences between humans and NHP that could lead to such starkly contrasting outcomes. Herein, we explore the potential benefits and drawbacks of the decedent model and contrast it to the advantages and disadvantages of the extensive body of data generated in the NHP xenoheart transplantation model.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Terapia de Inmunosupresión
Tipo de estudio:
Clinical_trials
/
Etiology_studies
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Guideline
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Prognostic_studies
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Risk_factors_studies
Límite:
Animals
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Humans
Idioma:
En
Revista:
Am J Transplant
Asunto de la revista:
TRANSPLANTE
Año:
2024
Tipo del documento:
Article