Despite considerable effort to halt or delay destruction of β-cells in autoimmune type 1 diabetes (T1D), success remains elusive. Over the last decade, we have seen a proliferation of knowledge on the pathogenesis of T1D that emerged from studies performed in non-obese diabetic (NOD) mice. However, while results of these preclinical studies appeared to hold great promise and boosted patients' hopes, none of these approaches, once tested in clinical settings, induced remission of autoimmune diabetes in individuals with T1D. The primary obstacles to translation reside in the differences between the human and murine autoimmune responses and in the contribution of many environmental factors associated with the onset of disease. Moreover, inaccurate dosing as well as inappropriate timing and uncertain length of drug exposure have played a central role in the negative outcomes of such therapeutic interventions. In this review, we summarize the most important approaches tested thus far in T1D, beginning with the most successful preclinical studies in NOD mice and ending with the latest disappointing clinical trials in humans. Finally, we highlight recent stem cell-based trials, for which expectations in the scientific community and among individuals with T1D are high.

The rise, fall, and resurgence of immunotherapy in type 1 diabetes / M. Ben Nasr, F. D'Addio, V. Usuelli, S. Tezza, R. Abdi, P. Fiorina. - In: PHARMACOLOGICAL RESEARCH. - ISSN 1043-6618. - 98(2015), pp. 31-38.

The rise, fall, and resurgence of immunotherapy in type 1 diabetes

M. Ben Nasr;F. D'Addio
Secondo
;
V. Usuelli;P. Fiorina
Ultimo
2015

Abstract

Despite considerable effort to halt or delay destruction of β-cells in autoimmune type 1 diabetes (T1D), success remains elusive. Over the last decade, we have seen a proliferation of knowledge on the pathogenesis of T1D that emerged from studies performed in non-obese diabetic (NOD) mice. However, while results of these preclinical studies appeared to hold great promise and boosted patients' hopes, none of these approaches, once tested in clinical settings, induced remission of autoimmune diabetes in individuals with T1D. The primary obstacles to translation reside in the differences between the human and murine autoimmune responses and in the contribution of many environmental factors associated with the onset of disease. Moreover, inaccurate dosing as well as inappropriate timing and uncertain length of drug exposure have played a central role in the negative outcomes of such therapeutic interventions. In this review, we summarize the most important approaches tested thus far in T1D, beginning with the most successful preclinical studies in NOD mice and ending with the latest disappointing clinical trials in humans. Finally, we highlight recent stem cell-based trials, for which expectations in the scientific community and among individuals with T1D are high.
B cells; Hematopoietic stem cells; Immunosuppression; Immunotherapy; NOD mice; T cells; Type 1 diabetes; Animals; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Drug Evaluation, Preclinical; Humans; Immunotherapy; Pharmacology
Settore MED/13 - Endocrinologia
2015
Article (author)
File in questo prodotto:
File Dimensione Formato  
Pharmacol Res 2014.pdf

accesso riservato

Descrizione: Articolo principale
Tipologia: Publisher's version/PDF
Dimensione 1.2 MB
Formato Adobe PDF
1.2 MB Adobe PDF   Visualizza/Apri   Richiedi una copia
Pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/484618
Citazioni
  • ???jsp.display-item.citation.pmc??? 16
  • Scopus 55
  • ???jsp.display-item.citation.isi??? 43
social impact