One of the main causes of blindness in the world, age-related macular degeneration (AMD) is a silent disease that affects millions of elderly people worldwide, causing the death of retinal pigment epithelium (RPE) cells and forming areas of atrophy.
In other words, the image in the center of the visual field begins to become blurry, distorted, or glitchy, as if a piece is missing. When the disease is already in an advanced stage, called geographic atrophythe patient begins to notice dark, grayish or transparent spots that gradually increase.
Now, scientists from the University of Michigan, the Neural Stem Cell Institute and Luxa Biotechnology have announced the first results of an unprecedented clinical trial, which uses adults to restore vision in patients with the dry form of the disease, considered, until now, to be irreversible.
According to the study, the strategy is to use adult stem cells — already destined to form only the retinal pigment epithelium — to repopulate areas of atrophy with new functional cells.
Obtained from deceased donors, these cells are cultured for four weeks until they reach an ideal stage for transplantation. The idea is that they can replace lost tissuewith more safety and less risk of generating tumors.
What was the first stem cell trial in patients with dry AMD like?
Conducted by reference centers in the USA, the clinical trial is . As this is an initial study (phase 1/2a), the researchers’ objective was to verify safety and observe early signs of effectiveness, before progressing to larger tests.
Stem cells, by definition, have the potential to transform into different cell types, which, on the one hand, is an advantage, but can also be a risk, when they are transplanted specifically into one of the most delicate and vulnerable tissues in the entire organism.
Therefore, in the transplant carried out in the retina of one of the eyes of the six volunteers in the clinical trial, 50 thousand RPESC-RPE-4W cells were used, an acronym that stands for adult stem cells taken directly from the retinal pigment epithelium of donors and cultured for four weeks.
The objective of this care is to ensure that they behave effectively as RPE cells, have their risk of tumors reduced, are in the ideal place to survive in the human eye, are able to repopulate the diseased area and support the photoreceptors, that is, the cells that convert light into electrical signals.
The results obtained in this first group of patients exceeded all expectations. The three most visually impaired achieved, in addition to an impressive improvement of 21.67 letters in the visual acuity test, a vision gain that reversed the natural history of the disease. Patients with moderate vision gained 3 letters.
A new hope for people at risk of losing their vision
The great difference of this study is biological safety: by using adult RPE cells in transplants, the authors guaranteed a supply of cells that, although still at a less mature stage, were already programmed to become only RPE cells and, therefore, could better integrate into the tissue.
With these positive results observed in the first group of patients, the team is now preparing to advance to the next phase of the study, which will test larger doses of cells (150 thousand and, later, 250 thousand cells). The therapy has already received RMAT designation from the FDA, which accelerates the development and evaluation of promising regenerative therapies.
Another relevant aspect when it comes to transplantation is immunosuppression. Although the study used immunosuppressive medications for six months, there were no signs of rejection even after discontinuation, suggesting that, as an ocular area with a low immune response, the retina may allow extensive immunosuppression to be dispensed with.
Experts point out that this approach could mark a turning point in the treatment of dry AMD. If the results are confirmed in larger groups of patients and with longer follow-up, .
This is no small feat, because most of these people live today without any therapeutic option capable of stopping geographic atrophy or recovering part of their lost vision. For this audience, the simple possibility of stabilization — let alone improvement — represents a profound change in the clinical horizon.
