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NIH grant 1R56AI196062-01A1: Pioneering new regimens to treat Mycobacterium avium complex pulmonary disease
Institute: {'code': 'AI', 'abbreviation': 'NIAID', 'name': 'National Institute of Allergy and Infectious Diseases', 'admin_org_id': '12500003', 'admin_funding_url': ''}. PI: Gyanu Lamichhane. Award: $703040.
Start: 2026-08-27T00:00:00.
PROJECT SUMMARY
The global incidence of non-tuberculous mycobacterial lung disease, particularly caused by Mycobacterium
avium complex (MAC), has surpassed tuberculosis (TB) in the U.S. MAC primarily affects individuals with
underlying lung conditions or compromised immunity, leading to rapid lung function decline and significant
morbidity and mortality. Unlike TB, which benefits from multiple FDA-approved drugs and extensive research,
MAC lung disease has only one FDA-approved drug (amikacin), and current treatments achieve a 3-year
microbiological cure rate of just 31%.
This proposal aims to develop innovative, effective regimens for MAC lung disease by leveraging novel
concepts and emerging evidence to address critical gaps in treatment. Specific Aim 1 focuses on developing
new regimens compliant with current guidelines requiring three or more drugs. Using a validated mouse model
of MAC lung disease, the study will evaluate combinations of existing and new antibiotics prioritizing regimens
that minimize drug resistance and treatment failure. Specific Aims 2 and 3 pursue pioneering ideas to innovate
radically different treatment approaches. Specific Aim 2 investigates dual β-lactams with synergistic activity
against MAC. Building on emerging evidence, this aim seeks to identify and test β-lactam pairs in vitro and in
mouse models to establish their efficacy for MAC lung disease. Specific Aim 3 challenges the need for
multidrug regimens in both treatment phases. Preliminary data suggest that simplified, phase-specific
regimens using one or two highly synergistic drugs may achieve equivalent or superior efficacy. This aim will
rigorously test these regimens to determine their potential to transform clinical practices. If successful, this
research will redefine MAC lung disease treatment by delivering optimized regimens that improve outcomes
and establish a new standard of care.document fetched 2026-09-06 02:47