The rise, fall, and resurgence of immunotherapy in type 1 diabetes
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,...
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| Published in | Pharmacological research Vol. 98; pp. 31 - 38 |
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| Main Authors | , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Netherlands
Elsevier Ltd
01.08.2015
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1043-6618 1096-1186 1096-1186 |
| DOI | 10.1016/j.phrs.2014.07.004 |
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| 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. |
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| AbstractList | 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.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. 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. |
| Author | Ben Nasr, Moufida D’Addio, Francesca Fiorina, Paolo Tezza, Sara Usuelli, Vera Abdi, Reza |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/25107501$$D View this record in MEDLINE/PubMed |
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| Keywords | Immunosuppression Type 1 diabetes Immunotherapy B cells NOD mice T cells Hematopoietic stem cells |
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a randomised double-blind trial publication-title: Lancet doi: 10.1016/S0140-6736(11)60895-7 |
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| Snippet | 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... |
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| SubjectTerms | Animals B cells Clinical Trials as Topic Diabetes Mellitus, Type 1 - immunology Diabetes Mellitus, Type 1 - therapy Drug Evaluation, Preclinical Hematopoietic stem cells Humans Immunosuppression Immunotherapy Immunotherapy - methods NOD mice T cells Type 1 diabetes |
| Title | The rise, fall, and resurgence of immunotherapy in type 1 diabetes |
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