CHICAGO — A cell-based therapy derived from umbilical cord tissue could someday treat geographic atrophy caused by age-related macular degeneration (AMD), early studies of this novel therapy suggest. "Advanced AMD is the leading cause of irreversible vision loss. Non-neovascular AMD, ie, dry AMD, geographic atrophy, has no approved treatment, and thus is an unmet medical need," said lead investigator Sheila Hickson-Curran, MCOptom, director of ophthalmology at the Janssen Pharmaceutical Companies of Johnson & Johnson.
Janssen is developing a cell-based product they have labeled palucorcel. In a phase 2b study, palucorcel was safely delivered to the subretinal space via a novel injection device passed into the suprachoroidal space. Imaging provided clear evidence of cell deposits around areas of atrophy, and microperimetry showed areas of retinal sensitivity improvement in some patients, Dr Hickson-Curran reported here at Academy 2017, the American Academy of Optometry's Annual Conference.
She emphasized that palucorcel is not stem cell therapy. "The cells do not change into tissue you may want to replace. Instead, they release tropic factors that can increase the functionality of the struggling [retinal pigment epithelium]. They have also been shown to release thrombospondins, proteins that increase neurite outgrowth and synapse formation in ganglion cells."
Interestingly, the cord tissue from which palucorcel was derived for use in this trial came from a baby born approximately 9 years ago. One umbilical cord can provide an almost endless number of cells, she said.
In an interview with Medscape Medical News, Dr Hickson-Curran was circumspect about the preliminary findings. "We cannot yet claim efficacy because our numbers are small and they do not come from a randomized controlled clinical trial, but this approach definitely has potential," she said.
"This is the third clinical trial with these cells, and what we have learned is that the cells can improve the vision of some patients with geographic atrophy. In the phase 1 trial, some gained at least 15 letters on [the Early Treatment Diabetic Retinopathy Study] chart, and this was sustained for at least 18 months."
Phase 2b Study Details
In her presentation here, Dr Hickson-Curran reported findings from the open-label component of the phase 2b PRELUDE trial, which will follow patients out to 5 years. Her talk focused on the safety of the surgical procedure and the evidence of an effect on imaging.
Twenty-one patients (mean age, 77 years) with geographic atrophy related to AMD enrolled in the trial. At baseline, mean best corrected visual acuity in their worst eye was 41 ± 11 Early Treatment Diabetic Retinopathy Study letters (approximately 20/160), and mean size of geography atrophy was 15.2 ± 7.5 mm2. The researchers injected palucorcel into the subretinal space of the worst-seeing eye.
Pre- and postsurgical imaging evaluated the presence of cell deposits and changes in retinal light sensitivity. Modalities included color fundus photography, optical coherence tomography, fundus auto-fluorescence, and microperimetry with the Macular Integrity Assessment microperimeter (CenterVue). A custom-designed 30-degree microperimetry grid was created to include the geographic atrophy area and the surrounding retina. In some cases, the grid also covered the cell deposit area.
Early Findings From PRELUDE
"Palucorcel was safely delivered to the subretinal space and could be observed using different imaging modalities," Dr Hickson-Curran reported. "And microperimetry detected changes in retinal sensitivity in some eyes."
When cells are delivered to the subretinal space, close to but not within the area of atrophy, they appear as white sheets or clumps, "settling with gravity and stacking up" near the lesion. "They seem to be acting as we would expect," she noted. "Over time we see the cell deposit areas changing on optical coherence tomography. We could visualize cells through at least 12 months."
Placement is very important. "If they are delivered too close to the part of the retina that the patient has adopted for seeing, because they have lost their fovea, then the cells can actually decrease retinal function," she explained.
Microperimetry maps specific points on the retina and enables the investigators to evaluate the function of those points over time. The device projects stimuli of differing brightness. Patients respond by clicking a button when the object is seen. This testing revealed postprocedural changes in light sensitivity around areas of atrophy.
Optimal placement of cells has resulted in maintenance of vision. "These are patients with advanced disease, so we don't expect much improvement in vision," she said.
The procedure proved safe, with no reports of retinal tears or detachments, significant hemorrhage in the choroid, cell egress into the vitreous, or endophthalmitis.
Novel Delivery System Also a Treatment Advance
"The delivery system is also very exciting because it's a new way to deliver drugs to the retina," Dr Hickson-Curran said. Rather than taking a transvitreal approach, this technique passes a 1.6-mm cannula containing a tiny needle through the suprachoroidal space, "going around the back," she said. The needle is advanced once the target position is reached, and the product is delivered into the subretinal space. "This is also a big breakthrough."
Session moderator Patrick A. Scott, OD, PhD, from the University of Louisville in Kentucky, said cell therapy has been an area of research in ocular diseases for some time but is now becoming more refined.
"Cell therapy is amazing because it is going to basically allow cells to produce neurotropic factors that the retina may be deficient in. Cells will be [an] exogenous source," he said. "Not only is there potential to actually help the retina tissue, but also the [retinal pigment epithelium] and the choroidal tissue. And in cases where vessels start to sclerose, delivery of these cells can help keep blood vessels intact and treat diseases like AMD."
Dr Scott conducts stem cell research for retinitis pigmentosa and has shown, in a model of congenital blindness, that the nutrients can be delivered via the injection of progenitor cells and that outer segment tissue can be regenerated and cell function increased.
In cell-based therapies, he said, "We are now refining the techniques, and trying to get the cells to stay where they need to stay."
Dr Hickson-Curran is an employee of Janssen Pharmaceutical Companies of Johnson & Johnson. Dr Scott has disclosed no relevant financial relationships.
American Academy of Optometry (AAOpt) Annual Conference. Presented October 12, 2017.
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Cite this: Cell-Based Therapy for Dry AMD Promising in Early Trial - Medscape - Oct 14, 2017.