Abstract
Technical Project Abstract
Choroideremia (CHM) is a rare X-linked recessive inherited retinal degeneration caused by mutations in the CHM gene, which disrupt Rab escort protein 1 (REP1) and impair membrane trafficking in the retina. Although gene augmentation therapies have led to cautious optimism, major clinical trials in choroideremia have shown how difficult it is to demonstrate meaningful benefit using best-corrected visual acuity (BCVA) alone. After the success of Luxturna, multiple subretinal adeno-associated virus (AAV)-based gene therapy programs moved forward in CHM, including Spark Therapeutics’ AAV2-hCHM program and NightstaRx/Biogen’s timrepigene emparvovec trial. Early studies suggested acceptable safety and possible maintenance or improvement in vision for some treated eyes, but results were variable and complicated by small sample sizes, surgical effects, and differences in baseline disease severity. Most importantly, the phase 3 STAR trial did not meet its primary endpoint of a ≥15-letter BCVA improvement, reinforcing the idea that BCVA may be poorly matched to the slowly progressive nature of CHM.
This project responds to that problem by asking which functional and structural endpoints may better capture clinically meaningful change in choroideremia patients, especially across age groups. Using data from the Natural History Study of the Progression of Choroideremia (NIGHT), obtained through a partnership between the Critical Path Institute and the Choroideremia Research Foundation, the analysis compared participants aged 40 years or younger with those over 40. Only participants with complete longitudinal data from screening through month 20 were included. In addition to BCVA, the project examined microperimetry, contrast sensitivity, ellipsoid zone metrics, and fundus autofluorescence in order to evaluate endpoints that may be more sensitive to disease progression than visual acuity alone. Age-stratified analyses were performed because functional preservation in CHM often remains relatively stable in younger patients before accelerating later in life.
The results showed clear and consistent differences between age groups. In both microperimetry and contrast sensitivity, younger participants maintained higher and more stable performance across visits, while older participants showed lower baseline function and greater variability. However, neither endpoint demonstrated a strong pattern of decline over the short study period, which further illustrates the challenge of selecting endpoints capable of detecting meaningful stabilization or treatment effect over two to five years. Taken together, this project argues that future CHM trials need better endpoints, better age stratification, and more refined patient selection criteria so that therapeutic benefit can be measured in ways that match the biology and time course of the disease.
STS Paper Abstract
My STS paper examines how media coverage shapes patient trust, expectations, and perceptions of uncertainty in the context of gene therapy, with inherited retinal diseases (IRDs) serving as the central case study. While gene therapy has extraordinary therapeutic potential, it is also complex, costly, and still marked by unresolved risks and highly variable outcomes. In spite of this, media narratives often frame gene therapy as miraculous, curative, and reliably transformative. I argue that these reports systematically construct gene therapy as a trustworthy intervention while minimizing uncertainty, variability, and experimental limitation. In rare-disease contexts such as IRDs, this framing contributes to therapeutic misconception, complicates informed consent, and may carry long-term consequences for public trust in emerging biotechnologies.
Methodologically, the paper combines discourse analysis with Actor-Network Theory (ANT). Discourse analysis allows me to identify recurring rhetorical patterns in media coverage, including curative language, miracle narratives, metaphorical restoration, selective authority, and compressed timelines. I complement this by using ANT to trace how journalists, biotech companies, regulators, patients, press releases, trial data, and media platforms collectively produce public meaning around gene therapy. Rather than treating hype as the product of one careless author or one misleading article, the paper shows that optimistic interpretations are stabilized through a broader sociotechnical network. This makes the media not just a passive messenger, but an active participant in how risk, benefit, and uncertainty are translated for the public.
My analysis found a significant amount of discursive certainty framing in gene therapy reporting, especially in IRDs. Headlines frequently described vision as being “restored” or “given back,” even when the underlying studies reported modest or heterogeneous outcomes. Risk and uncertainty were often delayed, minimized, or presented only as minor caveats after emotionally powerful success stories. Metaphors of light, miracles, and rebirth reinforced the idea that blindness is an inherent tragedy and that technological restoration is the natural solution, opening the discussion to disability studies and technoableism. Across these narratives, credibility was often constructed through the voices of researchers, biotech executives, and institutional representatives, while independent ethical or clinical perspectives were largely absent. I conclude that informed consent does not begin in the clinic; it begins with the media environment patients consume long before enrollment.
Connection Between the Projects
These two projects are connected because they examine the same biomedical problem from different directions. The technical project asks what endpoints actually matter for choroideremia patients and shows how difficult it is to measure meaningful benefit in a slowly progressive retinal disease. The STS project asks how gene therapy is publicly described and shows that media narratives often present those same therapies with more certainty than the evidence supports. Together, the projects taught me that the scientific and social sides of treatment development cannot be separated. The technical work showed me how much ambiguity, variability, and endpoint limitation still shape the evidence base. Applying my STS work to the technical components, I learned that those uncertainties are often reduced once the science is turned into consumable form for the general public. Each of my projects helped clarify the other. The technical side stressed why the caution is scientifically needed, and the STS side explained why it is ethically necessary.
