Inhaled Alpha 1-Antitrypsin: Gauging Patient Interest in a New Treatment

Monk, Richard; Graves, Michael C.; Williams, Pamela Holtzclaw; Strange, Charlie

doi:10.3109/15412555.2012.758698

Cited by 22 publications

(18 citation statements)

References 19 publications

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“…Many repeated articles and those with redundant content were eliminated. Finally, a total of 141 papers were selected . Where deemed appropriate, evidence‐based recommendations of the American College of Chest Physicians Task Force modified by the Canadian Thoracic Society COPD Clinical Assembly Alpha‐1 Antitrypsin Deficiency Expert Working Group were provided (Table ).…”

Section: Methodology Used For the Current Reviewmentioning

confidence: 99%

“…Significant progress is being made on potential new applications of AAT. For example, it appears that aerosolized AAT (nebulized or dry powder inhaled) could become clinically available for alpha and nonalpha patients with chronic obstructive pulmonary disease (COPD), cystic fibrosis, bronchiectasis or bronchial asthma . In addition, intravenous AAT has demonstrated efficacy in selected cases of autoimmune diabetes type 1, Crohn's disease, graft‐versus‐host disease, transplant rejection, multiple sclerosis, systemic vasculitis, fibromyalgia, chronic fatigue syndrome, rheumatoid arthritis, human immunodeficiency virus (HIV), influenza virus and other types of infection, relapsing panniculitis, myocardial infarction and possibly other inflammatory, immunological and infective disorders .…”

Section: Historic Perspectivementioning

confidence: 99%

“…Several studies with aerosolized human AAT have demonstrated its ability to inhibit neutrophil elastase and decrease IL‐8 concentration in the alveolar fluid, as well as to reduce neutrophil counts in sputum, with high safety, efficacy and tolerance . Also, a high‐purity liquid formulation of AAT has been developed for aerosol treatment, to respond to the interest of patients in the development of commercially available inhaled AAT replacement products . It is expected that with this approach, local lung concentrations of AAT can be achieved at low doses, sparing both systemic delivery of AAT and cost.…”

Section: Potential New Therapeutic Uses Of Aatmentioning

confidence: 99%

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Role of alpha‐1 antitrypsin in human health and disease

2014

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Alpha‐1 antitrypsin (AAT) deficiency is an under‐recognized hereditary disorder associated with the premature onset of chronic obstructive pulmonary disease, liver cirrhosis in children and adults, and less frequently, relapsing panniculitis, systemic vasculitis and other inflammatory, autoimmune and neoplastic diseases. Severe AAT deficiency mainly affects Caucasian individuals and has its highest prevalence (1 : 2000–1 : 5000 individuals) in Northern, Western and Central Europe. In the USA and Canada, the prevalence is 1: 5000–10 000. Prevalence is five times lower in Latin American countries and is rare or nonexistent in African and Asian individuals. The key to successful diagnosis is by measuring serum AAT, followed by the determination of the phenotype or genotype if low concentrations are found. Case detection allows implementation of genetic counselling and, in selected cases, the application of augmentation therapy. Over the past decade, it has been demonstrated that AAT is a broad‐spectrum anti‐inflammatory, immunomodulatory, anti‐infective and tissue‐repair molecule. These new capacities are promoting an increasing number of clinical studies, new pharmacological formulations, new patent applications and the search for alternative sources of AAT (including transgenic and recombinant AAT) to meet the expected demand for treating a large number of diseases, inside and outside the context of AAT deficiency.

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Section: Methodology Used For the Current Reviewmentioning

confidence: 99%

Section: Historic Perspectivementioning

confidence: 99%

Section: Potential New Therapeutic Uses Of Aatmentioning

confidence: 99%

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Role of alpha‐1 antitrypsin in human health and disease

2014

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“…In parallel, new types of AAT, new routes of administration and the physiologic, radiologic, and clinical readouts for AAT therapy are under development. These include the production of recombinant AAT and development of inhaled preparations of AAT ( Monk et al, 2013 ). An alternative strategy uses non-viral gene transfer, gamma-retrovirus, recombinant adenovirus (rAd), and recombinant adeno-associated virus (rAAV) vectors to express AAT.…”

Section: The State Of Clinical Development Of Aat Drugsmentioning

confidence: 99%

The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions

et al. 2018

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Neutrophils are the predominant immune cells in human blood possessing heterogeneity, plasticity and functional diversity. The activation and recruitment of neutrophils into inflamed tissue in response to stimuli are tightly regulated processes. Alpha1-Antitrypsin (AAT), an acute phase protein, is one of the potent regulators of neutrophil activation via both -protease inhibitory and non-inhibitory functions. This review summarizes our current understanding of the effects of AAT on neutrophils, illustrating the interplay between AAT and the key effector functions of neutrophils.

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“…However, twice daily inhaled therapy is preferred by patients compared with once weekly intravenous therapy. 33…”

Section: Rapidmentioning

confidence: 99%

Anti-Proteases and Alpha-1 Antitrypsin Augmentation Therapy

Strange

2018

Respir Care

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Alpha-1 antitrypsin deficiency is a genetic disease that first highlighted the importance of protease balance in normal lung homeostasis. Proteases such as neutrophil elastase are important in many pulmonary diseases. However, the first commercially licensed anti-protease therapy was used for emphysema in alpha-1 antitrypsin deficiency. The 4 commercial alpha-1 protease inhibitor preparations in the United States are currently given intravenously to augment the serum and alveolar epithelial lining fluid concentrations of alpha-1 antitrypsin. Since the discovery of alpha-1 antitrypsin deficiency in 1963, many genetic polymorphisms of the SERPINA1 gene have been discovered. Because neutrophilic inflammation is the hallmark of usual COPD, anti-protease therapy also has been explored in this disease. Further trials with different dosing schema, inhaled therapy, and in different disease states are all ongoing. These studies would be facilitated by having COPD outcomes that are independent of measurement of air flow and achievable in smaller populations over a short period of time.

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Inhaled Alpha 1-Antitrypsin: Gauging Patient Interest in a New Treatment

Abstract: There is a high level of patient interest in the development of a commercially available inhaled AAT replacement product.

Cited by 22 publications

References 19 publications

Role of alpha‐1 antitrypsin in human health and disease

Role of alpha‐1 antitrypsin in human health and disease

The Multifaceted Effects of Alpha1-Antitrypsin on Neutrophil Functions

Anti-Proteases and Alpha-1 Antitrypsin Augmentation Therapy

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