Genetic Signature to Predict NAC Efficacy in Treating Idiopathic Pulmonary Fibrosis (IPF)
SUMMARY
- N-Acetylcysteine (NAC) is commonly used to break down mucous and lessen lung function decline but has traditionally shown low efficacy in treating patients with idiopathic pulmonary fibrosis (IPF). The only two FDA approved drugs to treat IPF have severe side effects, meaning there is an urgent need to find alternative treatment options.
- The inventors identified two genes, TOLLIP and MUC5B, that play an important role in protecting the lungs from an autoimmune response. They investigated whether mutations in these specific genes were related to patient response to NAC therapy.
- The invention is a molecular signature of two single nucleotide polymorphisms (SNPs) that can predict whether NAC treatment will improve or worsen the progression of IPF in patients. Therefore, the invention opens the potential for a new IPF therapy in an estimated 25% of affected patients.
- 315 IPF patients were surveyed in a prospective clinical trial. Results showed that a specific genotype was significantly predictive of response to NAC therapy (p=0.03) as compared to other possible genotypes (p=0.10).
FIGURE
The 315 IPF patients in the study were either treated with NAC (A) or untreated (B) and all patients in the study were genotyped. The results show that patients with the TT genotype were significantly more responsive to NAC therapy as compared to the TC and CC genotypes.
ADVANTAGES
ADVANTAGES
- Prevents administration of un-beneficial therapeutics
- Potentially allows for new indication of NAC
APPLICATIONS
- Precision medicine
- Clinical trials selection
- Drug repurposing
PUBLICATION
- US: 15/567,988, European patent pending