Three claims about the first ER-100 gene therapy results require different evidence: better vision, tissue rejuvenation and a longer healthspan, says biologist George Murphy

Three claims about the first ER-100 gene therapy results require different evidence: better vision, tissue rejuvenation and a longer healthspan, says biologist George Murphy

On November 2, George Murphy, co-founder of Boston University's Center for Regenerative Medicine, discussed the first ER-100 data on The ReProgram podcast. This gene therapy temporarily induces retinal cells to produce three proteins intended to restore a more youthful pattern of gene expression. On October 8, Life Biosciences reported that, in its phase one safety trial, two of three participants with glaucoma had improved visual field test results after 56 days. Murphy sees this as a reason to study the therapy further.

If future trials confirm sustained improvements in vision, Murphy proposes distinguishing three claims. The first is clinical benefit: a person sees better or loses vision more slowly. The second is tissue rejuvenation. This requires evidence linking the intervention to biological changes and improved tissue function, because protection, compensation or better function in surviving cells could also account for the improvement. Glaucoma specialist James Tsai, who is not involved in the trial, suggested a similar possibility in Business Insider: the therapy may simply have enhanced existing electrical signals in patients who retained some vision. The third is a longer healthspan. The heart, immune system and brain each present distinct challenges in delivering the therapy, with different biology, outcome measures and risks, so this claim requires separate, larger studies.

A visual field test maps sensitivity to light. The person looks at the centre of the field and indicates when they see flashes at different locations. At each location, the instrument determines the faintest detectable flash (the threshold is expressed in decibels). According to the press release, at least 28% of the tested locations improved by more than 4 decibels in each of the two participants.

Murphy identifies other possible reasons for the improvement. A learning effect from repeated testing has also been documented in people with suspected glaucoma. If a baseline measurement happens to be unusually poor, the next result can look better even without treatment. The trial registry describes the trial as open-label: clinicians and participants know that treatment is being given, and expectations may influence responses in a test that depends on the participant's attention. Each participant's results are compared with their own baseline. With many test locations and visits, some improvements may occur by chance. The test locations within one eye belong to a single biological system: “Several improved test locations in one eye do not amount to several independent patients.”

Other measurements listed in the registry for days 56 and 112 could corroborate the visual field improvement, including visual acuity (reading letters on a chart) and the retina's electrical response. Production of these proteins is switched on by the antibiotic doxycycline, which participants take for 56 days, so the measurement on day 112 will show whether the improvement persists after protein production is switched off. Murphy says: “Stopping production of a biological factor and reversing everything it has already changed are different tasks.”

In Murphy's view, a useful treatment enables tissue to function better with an acceptable long-term safety profile. A molecular analysis suggesting that the tissue is younger may help explain that result. He wants to see data tracking each participant over time; comparison with a control group and independent assessment of the results; benefits that people can notice themselves; and replication in a larger group and at other centres. In the episode description, he writes: “A treatment can be a major medical advance without proving that ageing has been reversed.”