Alpha 1-Antitrypsin Deficiency Clinical Trial
Official title:
Defining Epigenetic Regulation of Immunity in Alpha-1 Anti-trypsin Deficiency
The investigators hypothesize that environmentally influenced histone modifications regulate AM mediated inflammation, contributing to a variable clinical course of AATD, and may also influence or be influenced by the activity of AAT augmentation therapy.
The variable natural clinical course of alpha-1 anti-trypsin deficiency (AATD) disease and
strong influence of environmental exposures such as smoking, implicate a major role for
epigenetic mechanisms in modifying AATD disease penetrance. The goal of this study proposal
is to investigate epigenetic regulation of alveolar macrophage (AM) inflammation and function
in AATD PiZZ (two Z genes) and PiMZ (one M and one Z gene) patients. The investigators
proposal focuses on epigenetic histone modifications and gene expression specifically in AM.
AAT augmentation therapy, which alters disease symptoms, may also modulate AM epigenetics. To
identify epigenetic regulation of AM inflammation in AATD in the context of AAT therapy, the
investigators will perform and computationally integrate ChIP-seq and RNA-seq data. This will
help elucidate the immunomodulatory mechanisms regulating AATD and provide an epigenetic map
for diagnosis and targeted treatment. The investigators will test the efficacy of
FDA-approved histone modifying drugs, such as Suberoylanilide Hydroxamic Acid (SAHA) and more
specific next-generation histone modifiers, such as GSK-J4, to modulate AM AATD-associated
activity ex vivo.
The goal of this study is to enroll up to a total of 13 AATD cases and 6 healthy controls.
All AATD patients will be asked to give a blood sample and/or undergo a bronchoscopy. AATD
patients will also be asked to undergo a follow up bronchoscopy and/or blood draw after 6
months if treatment with alpha-1 antitrypsin augmentation therapy is initiated to study the
changes in these markers after augmentation therapy.
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