Latest research – 5

In our last newsletter of February 2021, we reported what kind of studies are currently ongoing. We also reported that there are studies on Glaucoma and Leber, among others, which are expected to be very interesting for us as ADOA patients. This is because the underlying problem has strong similarities. For example, we found an article about a study into Glaucoma and we put a number of questions to the researcher involved. The research focuses on the possibility of getting new healthy (RGC) cells in the eye. These cells have long branches to the brain and are what provide of your vision (this is a very brief summary of how this works, but it is the core of the story!). Here is a short report of the questions and  answers we received from the relevant researcher;

We spoke with Thomas V Johnson. He is a clinician-scientist and neuroscientist who, in addition to an ophthalmologist, eye surgeon and glaucoma specialist, also runs a translational science laboratory at Johns Hopkins Wilmer Eye Institute. They are studying the potential of stem cell transplantation to be used to achieve retinal ganglion cell (RGC) replacement and optic nerve regeneration for patients with optic neuropathies, including ADOA. In addition to running his own laboratory, he is co-director of the Hopkins Optic Nerve Regeneration Initiative.

Mr. Johnson answered the following questions for us;

Does this research also apply to ADOA and ADOA +?
Our work is very applicable to patients with ADOA. We envision that transplantation of stem cell-derived RGCs into the eye would have the potential to repopulate RGCs lost to a number of different optic neuropathies, including: ADOA, glaucoma, ischemic optic neuropathy, optic neuritis, Leber optic neuropathy, traumatic optic neuropathy. neuropathy and others.

What phase are you in now? And how long would it take to really get a therapy or medicine (also for ADOA)?
We are currently in the preclinical stage. We work with human stem cells and create human RGCs in the lab, but our scientific transplantation work is currently being performed in animal models of optic neuropathies, including rodents and non-human primates. Knowing when our successes in the laboratory and the safety of our approaches will provide enough supportive data to move forward with human clinical trials is a major challenge. We currently expect this possibility in 8-10 years. Of course, the faster we can conduct experiments in the laboratory (made possible with research funding from foundations and donors to support more scientists in laboratory doing the work), the sooner we expect to be able to conduct human clinical trials. Clinical trials in human patients would likely take about 2-4 years, and only if those studies demonstrated safety and efficacy, would RGC transplantation therapy become more generally available to patients on a widespread basis. 

Do you expect stabilization or improvement of your vision?
If our stem cell-derived neuronal transplantation approach works, we expect to see not only vision stabilization, but actual vision improvement / return. Vision loss in optic nerve disease develops as a result of RGC death and optic nerve atrophy. The aim of our work is to transplant human stem cell- derived RGCs into eyes with optic nerve damage and have these new RGCs integrate into the eye and send signals to the brain. By ‘replacing’ the damaged or degenerated RGCs, these transplanted neurons can be the first therapy capable of actually restoring vision in optic nerve disorders, including ADOA

What would a treatment look like?
At this point it is probably too early to know much detail about what the treatment would entail. However, I expect that much of the prep work prior to surgery will take place in a tissue engineering laboratory where human stem cells are manipulated and differentiated into donor replacement RGCs. A patient would then undergo transplantation of the donor RGCs into the eye during surgery in the operating room, which would likely require a number of other existing standard surgeries to prepare the eye for transplantation including: pars plana vitrectomy (removal of the gel from the center of the eye) and possibly internal limiting membrane peeling. During the same surgery, donor RGCs would then be transplanted into the eye using a vehicle/carrier such as a gel or scaffold, and the patient would wake up and go home to return for clinical follow-up. While recovery from surgery to the patient’s pre-operative level of vision may not take too long (days or a few weeks), it would likely require months for the donor RGCs to generate new connections between the eye and brain, and actually begin to restore the vision that had been lost to ADOA or another optic nerve disease. Again, at this point in time these details are primarily conjecture, but this is the direction in which we envision our scientific work is heading. 

You can read the entire research here: https://www.ophthalmologytimes.com/view/a-rift-in-the-retina-may-help-repair-the-optic-nerve