Family and Caregiver Perspectives on Gene Therapy for Rett Syndrome

Abstract

Rett syndrome (RTT) is a neurodevelopmental disorder that primarily affects females and can result in cognitive impairment, seizures, spasticity, breathing problems, gastrointestinal issues, motor impairment, and behavioral concerns. Although gene therapy studies in patients with RTT will begin in the near future, there is no published research evaluating the attitudes and opinions of family members and caregivers of RTT patients towards gene therapy. This study addresses this gap in the literature using a mixed-method approach. Sixty-six caregivers of individuals with RTT completed an online survey asking about their previous experience in research and questions pertaining to their understanding of gene therapy, their expectations, as well as their hopes and concerns for treating RTT. Of the 66 individuals that completed the survey, ten respondents also participated in online focus groups which were evaluated using a thematic analysis. Overall, most of the participants (95.45%) had heard about gene therapy. A majority of the individuals (69.84%) had learned about it from a Rett syndrome foundation website. More than half of the respondents reported being somewhat knowledgeable (68.18%) about gene therapy and less than 20% reported no understanding of gene therapy (18.18%). When asked what impact they would like gene therapy to have on the individual with Rett syndrome in their lives, almost half (49.21%) ranked ‘cure the disorder’ as their number one choice, followed by ‘improve communication skills’ (19.05%), ‘improve gross motor skills’ (11.11%), and ‘improve language skills’ (9.52%). When asked the highest level of risk they would accept when enrolling the individual with Rett syndrome in a gene therapy clinical trial, almost half (47.69%) stated they would accept a low risk, and less than a tenth indicated they would accept a high risk (7.69%). In the focus groups, individuals discussed barriers to gene therapy, their hopes and concerns regarding gene therapy treatment, and how they would like to receive information about future research and therapies. Anticipated barriers to enrollment in clinical trials included time commitment, cost, distance to the trial site, unknown side effects, insufficient local medical support, negative experience with previous research, and potential exclusion from future trials. Participants had concerns about possible side effects of gene therapy, including physical and mental harm, a potential decrease in quality of life, irreversibility of the treatment, and whether individuals with RTT would want to “change who they are”. With gene therapy clinical trials on the horizon, understanding caregiver opinions will be important in setting goals and evaluating success of current studies, identifying and addressing barriers to trials and treatment, and in the development and implementation of educational resources for gene therapy in RTT.