2023-11-27 02:28:07
Madrid
NGEL NAVARRETE
graphic report
Updated Monday, November 27, 2023 – 01:28
Cure blindness. Esther Gallardo has always been concerned about rare pathologies and specifically those that affect the eyes. They have caught my attention since the race. The researcher at the Hospital 12 de Octubre Research Institute (i+12) leads a group with a pioneering project in the world: creating healthy retinal ganglion cells to remedy the progressive blindness of dominant optic atrophy.
It is a quite disabling situation for patients. Many of them may suffer legal blindness, says Gallardo. Focusing on optic neuropathies means finding a definitive solution or at least one that affects it, because there is no treatment for this type of disease.
To achieve this, it has a team that includes a neuro-ophthalmologist among its ranks. Alberto Reche, who belongs to the Ocular Motility and Neuro-ophthalmology section of the Madrid hospital, explains that this disease affects one in every 50,000 individuals. It is detected almost by chance in consultations, he explains.
This rare ocular pathology is progressive, so total vision loss occurs in advanced age. It depends on the patient. But at 65-70 years old they usually stop seeing almost completely. Thus, dominant optic atrophy is one of the most frequent forms of hereditary optic neuropathy that leads to a specific degeneration of retinal ganglion cells (RGCs), which compromises the transmission of visual information from the retina to the brain.
As Reche points out, it is about ‘fixing’ those lost nervous connections with the brain. Through that cable that connects the retina to it, the retinal ganglion cells circulate, a type of optic neurons, which become ill.
We are going to use the patients’ stem cells, reprogram them, grow them and place them healthy in their eyes
How? There is no single answer. It could be due to inflammation, ischemic problems, or toxins…. And what does it mean? One always sees badly. Little by little he loses sight, details Reche. But he points out that it is not a problem that can be solved with glasses. It is more complex.
As soon as you go to the optician’s office or see an ophthalmologist, it is detected. It can be hereditary, or appear suddenly in a generation, the neuro-ophthalmologist points out. Reche is in charge of the clinical part of the investigation. From his office, which treats a dozen patients with this atrophy, stem cells have been extracted from those affected to be used in research with the aim of returning them in the future converted into healthy retinal ganglion cells with the capacity to restore their vision.
From a blood sample, a small tissue sample or biopsy we extract the patient’s own cells, explains Gallardo. Right now they are in the middle of phase two of the investigation. At this time they have managed to develop induced pluripotent stem cells (iPSCs), a type of biological unit created in the laboratory that can give rise to any type of cell in the body, such as retinal ganglion cells. This project now knows how to create the drug, or as the researcher explains, we have personalized therapy, the reprogrammed IPSCs, but we still need to develop the manufacturing process. It must be as safe and effective as possible.
The growth of the cells is reviewed under the microscope.NGEL NAVARRETE
We rejuvenate the stem cells we extract to the point where they can be reprogrammed, like embryonic cells, but without as many ethical problems, says Gallardo.
This is the first phase of the project that has lasted a year. In the search and production of materials to generate this type of cells they have had to look for a plan B. You don’t always get everything the first time in Science. Gallardo points out that for the moment we have achieved the development of the cells, but only partially because the ones created are mixed with other [unas ms maduras otras menos], that is, they do not have sufficient purity and, furthermore, they are not generated in sufficient numbers, barely 30% of what is necessary. And if that is implanted in a patient, it could lead to tumors or pathological processes.
Help to jump over obstacles
In this part of the process, as in some others, private economic participation is necessary. In this case, from ONCE, who finances the search for solutions. Currently, as the i +12 researcher details, the problem lies in the materials that are used as a support for the cultivation, maintenance and expansion of both the iPSCs and the RGCs obtained from them.
They are expensive, present many ethical problems, have low production, low reproducibility between batches and a very complex physicochemical nature, he argues. Here another important leg of the investigation comes into play. In the end, in this type of project, multidisciplinary collaboration is essential. We cannot do everything from a single department in a laboratory, Gallardo insists. That is why we have neuro-ophthalmologists and experts in biomaterials.
To achieve the ecological niche or the best product, there is Miguel Ladero. The Department of Chemical Engineering and Materials of the Faculty of Chemical Sciences of the Complutense University of Madrid (UCM) will be in charge of creating the best conditions for the cells. We are going to help them feel at home, he says.
Getting the best cells is important because their effectiveness in recovering vision in patients will depend on their quality and quantity. Until now, we did not produce sufficient quantities in the culture media we used. A lot had to be purified and at the time of sifting there were not many valid cells left, Gallardo laments.
Laredo has the mission of designing the medium in which the cells will grow. And it is not an easy task to grow cells. You have to prepare the ground well. We have observed that smooth surfaces are not appropriate, says the researcher.
For this reason, in the biomaterials laboratory at UCM Laredo they will create reliefs on the surfaces to facilitate the cell’s axon to grow easily. How is this done? In the culture media we are going to create mini grooves or channels at a nanometer level, the expert emphasizes. These paths or grooves will be made through pulses of a laser. It will be done in a very controlled way, because if we decide that it is a rectangular groove, it has to be like that. To do this we use a very specific technique with a femtosecond laser. Come on, extremely fast, Laredo specifies.
It sounds strange, but Gallardo simulates by sliding his hands and fingers how a retinal ganglion cell extends, up and down as if it were the tentacles of an octopus. It is not only necessary to get the cells, but also for them, like a neuron, to behave like one, to have electrical activity. It is perfectly prepared to perform its function to restore sight to the patient.
There is still no date for the first trials in people. It is difficult to estimate a time. It is true that so far we have gone faster than expected. But in Science everything is very variable, Gallardo apologizes for not venturing into a specific announcement. However, he highlights his explanation with good news: Any of the results we obtain in these projects can be extrapolated to any other type of optic neuropathy. This would mean that pathologies such as glaucoma, which affects two million Spaniards, could benefit.
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