T2 Lentivirus GM-CSF gene therapy ameliorates autoimmune pulmonary alveolar proteinosis

Lund‐Palau, Helena; Meng, Cuixiang; Pilou, A; Atsumi, N; Bhargava, Aayushi; Chan, Mark; Byrne, AJ; Pringle, Ian A.; Ashworth, R C; Gill, Deborah R.; Hyde, Stephen C.; Morgan, Cliff; Alton, Ewfw; Griesenbach, Uta

doi:10.1136/thorax-2018-212555.2

Cited by 3 publications

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“…These sorts of model systems will undoubtedly be used more extensively to test novel treatments in the future. Gene therapy is also postulated as a treatment for autoimmune PAP; in both a murine model and ex vivo air–liquid interface cultures, transduction using a lentiviral vector carrying GM-CSF cDNA led to reduced BAL turbidity and long-term increases in GM-CSF [ 106 ]. Another study demonstrated that instillation of either wild-type or CSF2RB −/− gene-corrected, bone marrow-derived macrophages directly into the murine lung corrected lung disease, with persistence of the functioning macrophages in BAL for ≥12 months after a single administration[ 107 ].…”

Section: Treatment Optionsmentioning

confidence: 99%

Pulmonary alveolar proteinosis in children

Bush

Pabary

2020

Breathe

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Pulmonary alveolar proteinosis (PAP) is an umbrella term for a wide spectrum of conditions that have a very characteristic appearance on computed tomography. There is outlining of the secondary pulmonary lobules on the background of ground-glass shadowing and pathologically, filling of the alveolar spaces with normal or abnormal surfactant. PAP is rare and the common causes in children are very different from those seen in adults; autoimmune PAP is rare and macrophage blockade not described in children. There are many genetic causes of PAP, the best known of which are mutations in the genes encoding surfactant protein (SP)-B, SP-C, thyroid transcription factor 1, ATP-binding cassette protein 3, and the granulocyte–macrophage colony-stimulating factor (GM-CSF) receptor α- and β- chains. PAP may also be a manifestation of rheumatological and metabolic disease, congenital immunodeficiency, and haematological malignancy. Precise diagnosis of the underlying cause is essential in planning treatment, as well as for genetic counselling. The evidence base for treatment is poor. Some forms of PAP respond well to whole-lung lavage, and autoimmune PAP, which is much commoner in adults, responds to inhaled or subcutaneous GM-CSF. Emerging therapies based on studies in murine models of PAP include stem-cell transplantation for GM-CSF receptor mutations.Educational aimsTo understand when to suspect that a child has pulmonary alveolar proteinosis (PAP) and how to confirm that this is the cause of the presentation.To show that PAP is an umbrella term for conditions characterised by alveolar filling by normal or abnormal surfactant, and that this term is the start, not the end, of the diagnostic journey.To review the developmental differences in the spectrum of conditions that may cause PAP, and specifically to understand the differences between causes in adults and children.To discuss when to treat PAP with whole-lung lavage and/or granulocyte–macrophage colony-stimulating factor, and review potential promising new therapies.

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Section: Treatment Optionsmentioning

confidence: 99%

Pulmonary alveolar proteinosis in children

Bush

Pabary

2020

Breathe

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“…Using our lentiviral vector, we have been able to demonstrate apparently therapeutic levels of human α1-antitrypsin for up to 2 years in normal mice 57 and in a murine model of alveolar proteinosis were able to correct the clinically relevant phenotypic markers of the disease 58 . Further, we note that when sufficiently high levels of secreted proteins can be produced within the lungs, there is spill-over into the circulation.…”

Section: Beyond Cf; Secreted Versus Membrane Proteinsmentioning

confidence: 99%

Gene Therapy for Respiratory Diseases: Progress and a Changing Context

et al. 2020

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Review of the British Thoracic Society Winter Meeting 2018, 5–7 December 2018, London, UK

Goodwin

Singanayagam

Jenkins

2019

Thorax

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IntroductionThe Winter Meeting of the British Thoracic Society (BTS) is a platform for the latest clinical and scientific research in respiratory medicine. This review summarises some key symposia and presentations from the BTS Winter Meeting 2018.MethodsKey symposia and research presentations from the BTS Winter Meeting 2018 were attended and reviewed by the authors.ResultsThe seminal messages from the latest clinical and scientific research covering a range of respiratory diseases, including asthma, interstitial lung disease, infection, cystic fibrosis, pulmonary vascular disease, pleural disease and occupational lung disease were summarised in this review.DiscussionThe BTS Winter Meeting 2018 brought the very best of respiratory research to an audience of scientists, physicians, nurses and allied health professionals. The Winter Meeting continues to be a highlight of the UK respiratory research calendar, and we look forward to the next meeting in December 2019.

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T2 Lentivirus GM-CSF gene therapy ameliorates autoimmune pulmonary alveolar proteinosis

Cited by 3 publications

References 0 publications

Pulmonary alveolar proteinosis in children

Pulmonary alveolar proteinosis in children

Gene Therapy for Respiratory Diseases: Progress and a Changing Context

Review of the British Thoracic Society Winter Meeting 2018, 5–7 December 2018, London, UK

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