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Presented at AAO 2023, Russell Van Gelder, MD, PhD, discussed Abacus study and how KIO-301 targets low vision and end stage retinitis pigmentosa with visual acuity of light perception.
KIO-301, a voltage-gated potassium channel blocker which causes neurons to fire, can safely treat vision impairment, a new study found.
The Abacus study was a phase 1b open label, single ascending dose trial conducted in Australia with 2 cohorts and 6 enrolled patients. The first cohort, the no light perception (NLP) bear light perception cohort, had end stage retinitis pigmentosa with visual acuity of light perception. The second cohort, the low vision cohort, had low vision ranging from counting fingers to hand motion. For both cohorts, the primary endpoint was safety and tolerability. The trial design was a single dose escalation with low dose to 1 eye. The investigators measured safety, tolerability, and quality of life every month.
Russell Van Gelder, MD, PhD, of the department of ophthalmology at University of Washington School of Medicine presented his study at the 127th Annual American Academy of Ophthalmology (AAO) conference in San Francisco, California. He explained what a KIO-301 does, how if you were to put it on neuronal tissue it would be light dependent and have potential firing.
“If you apply this, for example, to the retina of an animal with end stage retinal degeneration… you see robust introduction of retinal ganglion cell firing in these retinas with no rods or cones in response to light,” Gelder said at the conference. “This is a potential means for visual restoration in individuals with even near complete loss of rods and cones in the outer retina.”
After the KIO-301 treatment, 1 patient experienced transient ocular hypertension and 2 experienced some discomfort after injections. Gelder and his colleagues did not find signs of either uveitis or retinal in the patients.
In cohort 1, the investigators assessed efficacy by the ability to detect light stimuli projected onto a screen. The team noted an increase of patients who could correctly identify the light on the screen, continuing to day 14 and remaining consistent to day 28 of the study.
Meanwhile, in cohort 2, the investigators used the Berkley rudimentary vision test to find the visual acuity after the higher KIO-301 dosage. The investigators noted improvement from hand motion to counting fingers which continued until day 29.
The team conducted real world essays, such as a walking distance direction test. Here, a participant was asked to answer which side an individual was walking across a visual field from behind a screen. Participants performed better after treatment. Also, the team conducted a high contrast room exit test, consisting of a maze participants had to walk through.
Gelder played a video of a participant expressing how nice the injection treatment was. After the injection, she could see significantly better.
“I walked into the supermarket, and I thought I was in a sci-fi movie,” the participant in the video said. “I’m standing. I’m looking around, and it was just bizarre because... I could see everything, every block of chocolate, all different colors. The things that were bright were really bright, and the things that were darker were really dark… Everything was so itemized.”
KIO-301 performed well in the studies, demonstrated its safety, tolerability, and effectively on an infection. Gelder said phase 2 of the trial will begin in 2024.
Gelder, R. Intravitreal Injection of “Photoswitch” Molecule (KIO 301) Improves Visual Function in Late-Stage Retinitis Pigmentosa Patients. Presented at the 2023 American Academy of Ophthalmology Annual Meeting, November 4, 2023.