Gene Therapy: Knowledge, Attitudes, and Preferences Among Individuals with Alpha-1 Antitrypsin Deficiency

Background: Gene therapy is a promising approach to treating alpha-1 antitrypsin deficiency (AATD). This study is the first to assess knowledge, attitudes, and preferences of the Alpha-1 patient community regarding gene therapies and gene therapy clinical trials. Methods: An electronic survey collected demographic and health characteristics among the AlphaNet population and assessed knowledge, attitudes, and preferences related to gene therapy using multiple-choice, Likert-scale, and open-ended questions. Results: Data were provided by 1,112 participants (98% on augmentation therapy and 18% with liver disease).The number of correct responses to knowledge-based questions varied (range: 0-12; mean: 5.8/12 ± 3.1; median = 6). While participants had generally positive perceptions of AATD gene therapy, attitudes and preferences differed between those at or above the knowledge median and those below. Those with higher knowledge were somewhat/very supportive of gene therapy research and development (56% vs. 43%), somewhat/very willing to participate in a gene therapy clinical trial (70% vs. 64%), and somewhat/very willing to receive an FDA-approved gene therapy (87% vs. 74%) (all p< 0.001). A gene therapy capable of targeting both liver and lung disease was preferred, along with therapies that require the least frequent re-dosing. Conclusion: This study identifies knowledge, attitudes, and opportunities to correct misconceptions related to gene therapy in the Alpha-1 community. Participants indicated desire for additional education, and increased knowledge was associated with more positive attitudes towards gene therapy. Thus, the benefit of educational efforts and materials may extend beyond the individual learner and also facilitate trial enrollment and therapy uptake.