The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
The Department of Genetic Medicine at Weill Cornell leads a dynamic and innovative translational research program, advancing diverse fields such as Genetic Therapy and Personalized Medicine.
Our translational research program aims to leverage our expertise in genetic therapies and personalized medicine to develop clinical solutions that target the molecular causes of human diseases.
The Department of Genetic Medicine advances treatments and diagnostics through diverse clinical trials, including drug testing and research to better understand diseases.
STUDY OBJECTIVE: To determine if aerosolization of purified human plasma alpha 1-antitrypsin is an effective means for increasing lower respiratory anti-neutrophil-elastase defenses in alpha 1-antitrypsin deficiency. DESIGN: Nonrandomized, before-and-after trial with a 7-day treatment period. Companion studies in animals to determine lung epithelial permeability to alpha 1-antitrypsin. PATIENTS: Twelve patients with homozygous Z-type alpha 1-antitrypsin deficiency and mild to moderate emphysema. INTERVENTIONS: Aerosol administration of human plasma alpha 1-antitrypsin, 100 mg every 12 hours for 7 days. Single, 100-mg aerosol dose to anesthetized sheep with indwelling thoracic lymph duct catheters for direct assessment of lung permeability. MEASUREMENTS AND MAIN RESULTS: Treatment resulted in increased alpha 1-antitrypsin levels in the lung epithelial lining fluid (0.28 +/- 0.07 microM before therapy to 5.86 +/- 1.03 microM after therapy) and increased anti-neutrophil-elastase capacity (0.78 +/- 0.38 microM before therapy to 4.16 +/- 0.95 microM after therapy). Aerosolized alpha 1-antitrypsin diffused across the respiratory epithelium and entered lung interstitial lymph (in sheep) and reached the systemic circulation (in sheep and humans). No side effects were noted. CONCLUSION: Short-term aerosol administration of human plasma alpha 1-antitrypsin to patients with alpha 1-antitrypsin deficiency is safe and feasible, resulting in a return to normal of anti-neutrophil-elastase defenses in the lower respiratory tract. The aerosol approach, therefore, merits serious long-term evaluation as an alternative to other parenteral forms of administering therapeutic proteins.