RARE DISEASE
Chronic respiratory distress with surfactant metabolism deficiency
Chronic respiratory distress with surfactant metabolism deficiency
Chronic respiratory distress with surfactant metabolism deficiency
Drug discovery
1
drug
With orphan designation
Overview
Chronic respiratory distress with surfactant metabolism deficiency (CRD-SMD) is a rare genetic interstitial lung disease caused by mutations in surfactant-related genes (SFTPB, SFTPC, ABCA3) [1][4][6]. It manifests variably, from neonatal respiratory failure in severe SP-B deficiency to chronic interstitial lung disease with cough, tachypnea, hypoxia, and failure to thrive in children/adults [4][6]. Diagnosis combines genetic testing, imaging (ground-glass opacities, cysts), and histopathology showing alveolar damage, fibrosis, and foamy macrophages [4][18].
Categories: rare genetic diseases, rare respiratory diseases, rare transplant-related disorders
Research Papers
85 drug discovery papers about Chronic respiratory distress with surfactant metabolism deficiency, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
85 drug discovery papers about Chronic respiratory distress with surfactant metabolism deficiency, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2024-07-06 | Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation
Abstract Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases. Graphical Abstract
2024-03-01 | A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic
Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic–ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.
2023-11-23 | Surfactant as a drug carrier
Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The inherent chemical properties of surfactant allows it to readily distribute throughout the respiratory system. Therapeutic agents delivered by surfactant can primarily confer additional benefits but have potential to improve the surfactant function. It is critically important that additional agents do not interefere with the innate surface tension lowering function of surfactant. Systemic evaluation through benchtop, translational and human trials to translate this potential technique into clinical practice.
2024-07-06 | Endogenous LXR signaling controls pulmonary surfactant homeostasis and prevents lung inflammation
Abstract Lung type 2 pneumocytes (T2Ps) and alveolar macrophages (AMs) play crucial roles in the synthesis, recycling and catabolism of surfactant material, a lipid/protein fluid essential for respiratory function. The liver X receptors (LXR), LXRα and LXRβ, are transcription factors important for lipid metabolism and inflammation. While LXR activation exerts anti-inflammatory actions in lung injury caused by lipopolysaccharide (LPS) and other inflammatory stimuli, the full extent of the endogenous LXR transcriptional activity in pulmonary homeostasis is incompletely understood. Here, using mice lacking LXRα and LXRβ as experimental models, we describe how the loss of LXRs causes pulmonary lipidosis, pulmonary congestion, fibrosis and chronic inflammation due to defective de novo synthesis and recycling of surfactant material by T2Ps and defective phagocytosis and degradation of excess surfactant by AMs. LXR-deficient T2Ps display aberrant lamellar bodies and decreased expression of genes encoding for surfactant proteins and enzymes involved in cholesterol, fatty acids, and phospholipid metabolism. Moreover, LXR-deficient lungs accumulate foamy AMs with aberrant expression of cholesterol and phospholipid metabolism genes. Using a house dust mite aeroallergen-induced mouse model of asthma, we show that LXR-deficient mice exhibit a more pronounced airway reactivity to a methacholine challenge and greater pulmonary infiltration, indicating an altered physiology of LXR-deficient lungs. Moreover, pretreatment with LXR agonists ameliorated the airway reactivity in WT mice sensitized to house dust mite extracts, confirming that LXR plays an important role in lung physiology and suggesting that agonist pharmacology could be used to treat inflammatory lung diseases. Graphical Abstract
2024-03-01 | A Review of the Use of Extracellular Vesicles in the Treatment of Neonatal Diseases: Current State and Problems with Translation to the Clinic
Neonatal disorders, particularly those resulting from prematurity, pose a major challenge in health care and have a significant impact on infant mortality and long-term child health. The limitations of current therapeutic strategies emphasize the need for innovative treatments. New cell-free technologies utilizing extracellular vesicles (EVs) offer a compelling opportunity for neonatal therapy by harnessing the inherent regenerative capabilities of EVs. These nanoscale particles, secreted by a variety of organisms including animals, bacteria, fungi and plants, contain a repertoire of bioactive molecules with therapeutic potential. This review aims to provide a comprehensive assessment of the therapeutic effects of EVs and mechanistic insights into EVs from stem cells, biological fluids and non-animal sources, with a focus on common neonatal conditions such as hypoxic–ischemic encephalopathy, respiratory distress syndrome, bronchopulmonary dysplasia and necrotizing enterocolitis. This review summarizes evidence for the therapeutic potential of EVs, analyzes evidence of their mechanisms of action and discusses the challenges associated with the implementation of EV-based therapies in neonatal clinical practice.
2023-11-23 | Surfactant as a drug carrier
Drug delivery using a surfactant vehicle has the potential to prevent systemic side effects by delivering therapeutic agents directly to the respiratory system. The inherent chemical properties of surfactant allows it to readily distribute throughout the respiratory system. Therapeutic agents delivered by surfactant can primarily confer additional benefits but have potential to improve the surfactant function. It is critically important that additional agents do not interefere with the innate surface tension lowering function of surfactant. Systemic evaluation through benchtop, translational and human trials to translate this potential technique into clinical practice.
Access all drug discovery articles and probability of success in trials forecasts:
Access all drug discovery articles and probability of success in trials forecasts:
Drug Discovery Landscape
1 orphan drug designation for Chronic respiratory distress with surfactant metabolism deficiency.
1 orphan drug designation for Chronic respiratory distress with surfactant metabolism deficiency.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
Bovactant | small molecules | EMA | 2022-02-24 | — | Aerogen Pharma Limited |
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI's forecasts to outperform average preclinical success rates. Whether you're expanding your R&D pipeline, evaluating a partnership, or simply have a question — we'd love to hear from you.