Pioglitazone as a novel therapeutic approach in chronic granulomatous disease

Migliavacca, Maddalena; Assanelli, Andrea; Ferrua, Francesca; Cicalese, Maria-Pia; Biffi, Alessandra; Frittoli, Marta Claudia; Silvani, Paolo; Chidini, Giovanna; Calderini, Edoardo; Mandelli, Anna; Camporesi, Anna; Milani, Raffaella; Farinelli, Giada; Nicoletti, Roberto; Ciceri, Fabio; Aiuti, Alessandro; Bernardo, Maria Ester

doi:10.1016/j.jaci.2016.01.033

Cited by 24 publications

(13 citation statements)

References 9 publications

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“…Other inflammatory diseases that underwent clinical trials with TZDs include sepsis where pioglitazone showed a significant reduction in inflammatory markers: IL-6, IL-8, resistin, and TNF-α in patients with severe sepsis or septic shock [278], lung inflammation where Chen et al (2018) concluded that pioglitazone had no anti-inflammatory effect in healthy volunteers based on 18 F-FDG PET/CT imaging [279], and chronic granulomatous disease where pioglitazone reduced CRP from 24.4 to 13.1 mg/L in a five-month old patient [280]. The efficacy of pioglitazone to treat patients with chronic granulomatous disease (NCT03080480), gastric phlogosis due to Helicobacter pylori infection (EUCTR 2005-001218-42), as well as lung inflammation in alcoholic individuals (NCT03060772) is being assessed in ongoing trials.…”

Section: Other Inflammatory and Infectious Diseasesmentioning

confidence: 99%

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Cheng

Tan

Low

et al. 2019

IJMS

167

152

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Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that govern the expression of genes responsible for energy metabolism, cellular development, and differentiation. Their crucial biological roles dictate the significance of PPAR-targeting synthetic ligands in medical research and drug discovery. Clinical implications of PPAR agonists span across a wide range of health conditions, including metabolic diseases, chronic inflammatory diseases, infections, autoimmune diseases, neurological and psychiatric disorders, and malignancies. In this review we aim to consolidate existing clinical evidence of PPAR modulators, highlighting their clinical prospects and challenges. Findings from clinical trials revealed that different agonists of the same PPAR subtype could present different safety profiles and clinical outcomes in a disease-dependent manner. Pemafibrate, due to its high selectivity, is likely to replace other PPARα agonists for dyslipidemia and cardiovascular diseases. PPARγ agonist pioglitazone showed tremendous promises in many non-metabolic disorders like chronic kidney disease, depression, inflammation, and autoimmune diseases. The clinical niche of PPARβ/δ agonists is less well-explored. Interestingly, dual- or pan-PPAR agonists, namely chiglitazar, saroglitazar, elafibranor, and lanifibranor, are gaining momentum with their optimistic outcomes in many diseases including type 2 diabetes, dyslipidemia, non-alcoholic fatty liver disease, and primary biliary cholangitis. Notably, the preclinical and clinical development for PPAR antagonists remains unacceptably deficient. We anticipate the future design of better PPAR modulators with minimal off-target effects, high selectivity, superior bioavailability, and pharmacokinetics. This will open new possibilities for PPAR ligands in medicine.

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Section: Other Inflammatory and Infectious Diseasesmentioning

confidence: 99%

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Cheng

Tan

Low

et al. 2019

IJMS

167

152

View full text Add to dashboard Cite

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“…That study showed that the risk of sepsis was reduced in patients under In the present study, we observed substantial differences in baseline characteristics and follow-up durations between the M+T and M+S regimen groups. 42 Moreover, in a mouse model of brain abscess induced by Streptococcus aureus, a PPAR-γ agonist significantly reduced the abscess-associated bacterial burden. We found that M + T treatment was associated with a lower risk of abscess development com- killing.…”

Section: Discussionmentioning

confidence: 99%

“…21 A case report showed that pioglitazone was a novel therapeutic approach for treating a 5-month-old boy with chronic granulomatous disease and multiple lung abscesses. 42 Moreover, in a mouse model of brain abscess induced by Streptococcus aureus, a PPAR-γ agonist significantly reduced the abscess-associated bacterial burden. 43 Another PPAR-γ ligand, ciglitazone, reduced S. pneumoniae-induced lung inflammation by suppressing bacterial outgrowth in a mouse model.…”

Section: Discussionmentioning

confidence: 99%

Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population‐based cohort study

Wang

Dong²,

et al. 2018

Diabetes Obesity Metabolism

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“…Apart from preexisting comorbidities and organ dysfunction, standard myeloablative conditioning protocols were also responsible for the striking transplant-related mortality observed in the past. Granulocyte infusions and more recently the use of pioglitazone, that can bypass the inability of NADPH oxidase complex by increasing mitochondrial reactive oxygen species, suggest relevant insights in the treatment of this rare disease [ 304 , 305 ].…”

Section: Hematopoietic Stem Cell Transplantation For the Treatmentmentioning

confidence: 99%

NADPH Oxidase Deficiency: A Multisystem Approach

Giardino

Cicalese

Delmonte

et al. 2017

Oxidative Medicine and Cellular Longevity

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The immune system is a complex system able to recognize a wide variety of host agents, through different biological processes. For example, controlled changes in the redox state are able to start different pathways in immune cells and are involved in the killing of microbes. The generation and release of ROS in the form of an “oxidative burst” represent the pivotal mechanism by which phagocytic cells are able to destroy pathogens. On the other hand, impaired oxidative balance is also implicated in the pathogenesis of inflammatory complications, which may affect the function of many body systems. NADPH oxidase (NOX) plays a pivotal role in the production of ROS, and the defect of its different subunits leads to the development of chronic granulomatous disease (CGD). The defect of the different NOX subunits in CGD affects different organs. In this context, this review will be focused on the description of the effect of NOX2 deficiency in different body systems. Moreover, we will also focus our attention on the novel insight in the pathogenesis of immunodeficiency and inflammation-related manifestations and on the protective role of NOX2 deficiency against the development of atherosclerosis.

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Pioglitazone as a novel therapeutic approach in chronic granulomatous disease

Cited by 24 publications

References 9 publications

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Exploration and Development of PPAR Modulators in Health and Disease: An Update of Clinical Evidence

Thiazolidinediones and reduced risk of incident bacterial abscess in adults with type 2 diabetes: A population‐based cohort study

NADPH Oxidase Deficiency: A Multisystem Approach

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