I’ve been in hiatus for a couple of years because—between breast cancer and a sudden, dramatic drop in vision that now hovers around light perception—I felt like I had been smashed in the face with a two-by-four. But like all of you who are determined to see your family’s faces and the world around you, I’ve continued to believe that an answer will materialize. And the new chemically induced retinal cell therapy developed by ophthalmologist and researcher Dr. Sai Chavala and his team might just be the miraculous, vision-restoring breakthrough we’ve all been channeling.
Before I get to the remarkable story behind this potentially game-changing therapy, here’s what I know you all want to know: Through a combination of cutting-edge research, trial and error and unrelenting determination, Dr. Chavala and his team have managed to convert ordinary human skin cells into functioning retinal cells by applying a proprietary chemical cocktail that serves as a reprogramming mechanism. And, at least in mouse models, they have been able to restore some sort of vision in completely blind mice.
Though it’s still in the pre-clinical trial phase, what this scientific breakthrough means for those of us suffering from RP is potentially so holy-crap-amazing it has taken the scientific world by storm–with the research data first published in the premier scientific journal, Nature, last year.
Here is what makes it so astounding:
Dr. Chavala started out as an ophthalmologist who planned to take over his dad’s eye practice in rural Missouri when he retired. But then he did a stint at the renowned Cleveland Clinic, where he was introduced to the research side of the equation, and was immediately intrigued. He realized he was in a unique position to merge his clinical expertise with breakthrough research that he hoped would result in vision-restoring therapies for patients suffering from blinding eye diseases.
“It was out of sheer frustration and helplessness that I pursued additional training in basic science,” he said. “The decision came from perpetually explaining to patients, some that had traveled from other countries to the world-renowned Cleveland clinic for a shred of hope, that there was simply nothing that could be done to improve their vision. The tears and dismay that ensued were heart breaking.
“As a trained physician, it was not appealing to take this unconventional departure from clinical training,” he added. “But I felt it was necessary to be able to have the skill set to create next generation medical therapies for eye disease.”
With the blessing of his boss at the Cleveland Clinic, Dr. Chavala went for it.
That was in 2009, when all the top scientific minds were focused on embryonic stem cells. Dr. Chavala read a cover story about it in a Time magazine article and began contacting all the scientists featured in the story.
“I got no response,” he said. “I had no research training and they were at the top of their game. I was going to give up, but then I went to a lecture for a world-renowned oncologist who was conducting cutting-edge stem cell research.”
Dr. Chavala Googled the oncologist and found his phone number on the internet. When he called the number, the doctor picked up.
“I gave him my heartfelt speech on why he had to take me into his lab and he agreed. It changed my entire path.”
While it might sound weird that Dr. Chavala would work with an oncologist, that’s where all the research dollars were earmarked, and it turns out that the parallels between stem cell therapies to treat cancer and eye diseases were striking. Dr. Chavala began cherry-picking applications from the cancer research to apply to the retina. After receiving extensive research training in New York, he underwent surgical training at Duke and eventually landed at the University of North Texas, where he received an NIH grant to start his own research experiments. In the meantime, breakthroughs in cell therapies had advanced to the point that skin cells were now being used as a replacement for embryonic stem cells which was the game changer Dr. Chavala’s team was looking for.
He and his team at the University of North Texas Health Science Center scoured published research as a starting point and then began experimenting with what felt like countless variations of chemicals and growth factors.
“We failed many times, to the point that we were going to give up,” admitted Dr. Chavala. Then it happened. The cells they were reprogramming turned green, which meant they had converted into retinal cells. “I was in disbelief, but I was cautious,” he said.
The next step was to inject the new retinal cells into mice that had lost all photoreceptor cells due to RP and were completely blind to see if they could actually work as functioning retinal cells. At the two-week mark, Dr. Chavala said there was no improvement. But three weeks after the chemically induced retinal cells were injected, his team noticed that the pupil was responding. Buoyed on by this accomplishment, they ran other tests with the mice that demonstrated that, at the very least, the mice could now differentiate between light and dark. This continued through the twelve-week mark—illustrating that synaptic connections were being made to the retina and that these cells were continuing to survive.
“After three months, we wanted to prove to people that the cells were doing something,” noted Dr. Chavala. “We euthanized them and sectioned the eyes. Sure enough, the cells were still green. Even after the chemicals were gone, they were still retinal cells.”
CiRC Biosciences, which was started by Dr. Chavala in an effort to get the retinal cell therapy to market, was recently acquired by Paragon Biosciences, which focuses on advancing life-changing therapies.
Tim Cunniff, Executive Vice President of Research and Development for Paragon, said the first step was achieving orphan drug designation from the FDA. This acknowledgement of the potential benefits of the retinal cell therapy for RP provides seven years of exclusivity (two years longer than other drug designations) so CiRC Biosciences has the necessary time to conduct the investigational research and clinical trials required to bring it to market. The next step, said Cunniff, is to conduct all the pre-clinical trial work required to establish safety and efficacy.
“We won’t just be replicating Dr. Chavala’s work,” noted Cunniff. “We will do experiments to determine if the order of chemicals added, the quantity of chemicals, or how long the chemicals are held in process improve results. It’s about optimizing everything.”
The investigational research is expected to take two years, with phase 1 and 2 clinical trials slated to begin in early 2023. That’s when we will begin to learn if this is, in fact, the key to reversing blindness and restoring sight in humans—regardless of how far our RP has advanced or what gene mutation we have.
There are still a lot of unknowns, such as how much vision can be restored and how long each dose of the chemically induced retinal cells will last. While there is still a ways to go before we’ll have the answers all of us are desperate to receive, the team at CiRC Biosciences, which will be conducting trials focused on both vision restoration and blindness prevention, are doing their best to fast track the process.
“We are very excited and hope to have this therapy on the market in seven years, which is very quick for these types of therapies” said Cunniff, noting that every person on his small team at Paragon—all of whom have deep expertise in the pharmaceutical and regulatory space—have put in personal funds to support CiRC Biosciences and will be intimately involved. “We know that reversing and preventing blindness is the holy grail and we are working as fast as we can. We are putting in the work on the front-end with the formulations and doing the robust studies necessary to save time in the long run.”