When I hear about groundbreaking studies like these, I always wonder who the courageous patient was who agreed to be the first to receive the treatment.  I don’t know if I’d personally have the chutzpah to be the first. The people who volunteer to be in these early-stage human studies for cutting-edge treatments are the true pioneers and heroes.

In addition to receiving a  potential treatment with very little (or no) track record in people, they have to make numerous clinical visits with extensive retinal exams and vision tests. Not only are they taking a risk, but clinical trial participants make a big commitment of time and energy.

I’d be remiss if I didn’t acknowledge the indispensible role of the clinicians and researchers who run the trials and perform the related procedures. They, too, are true pioneers. In the case of StemCells, Inc., Dr. David Birch is the principal investigator, with Dr. Rand Spencer performing the surgeries.

A researcher funded by the Foundation Fighting Blindness, Dr. Birch is no stranger to clinical trials. He currently serves as the principal investigator on human studies of valproic acid for the treatment of autosomal dominant retinitis pigmentosa (RP) and docosahexaenoic acid (DHA) for X-linked RP.

In recent years, he also led clinical trials of Neurotech’s encapsulated cell technology and Second Sight’s “bionic” retina. He clearly has a penchant and talent for living on the cutting edge of retinal research.

While the first results from the StemCells, Inc. study probably won’t be reported for a while, I look forward to reporting on them when they are announced. Stay tuned.

Pictured above: Dr. Rand Spencer, left, and Dr. David Birch, surgeon and lead investigator, respectively, in the StemCells, Inc., clinical trial.

All of the following, I might add, are being funded by the Foundation or were made possible by Foundation-funded preclinical research. I’ve categorized the trials by types of treatments and included links to articles or posts describing them in detail. Appended to each is the name of the company, facility or agency conducting and/or hosting the trial.

Gene Therapies

• Stargardt disease gene therapy — Oxford BioMedica
• Usher syndrome type 1B gene therapy — Oxford BioMedica
• Wet age related macular degeneration (AMD) gene therapy — Oxford BioMedica
• Wet AMD gene therapy — Genzyme
• Wet AMD gene therapy — Avalanche
• Choroideremia gene therapy — University of Oxford
• Retinitis pigmentosa (RP, MERTK) gene therapy — UCSD-King Khaled Eye Hospital
• Leber congenital amaurosis (LCA, RPE65) gene therapy — Children’s Hospital of Philadelphia
• Leber congenital amaurosis (LCA, RPE65) gene therapy — Universities of Pennsylvania and Florida

Cell-Based Therapies

• Stargardt disease treatment (RPE cells derived from stem cells) — Advanced Cell Technology
• Dry AMD treatment (RPE cells derived from stem cells) — Advanced Cell Technology
• RP and Usher syndrome (imaging study, encapsulated cell technology) — Neurotech
• Achromatopsia treatment (encapsulated cell technology) — National Eye Institute

Pharmaceuticals and Supplements

• Retinitis pigmentosa (autosomal dominant), valproic acid — FFB Clinical Research Institute
• LCA and RP (LRAT and RPE65), retinoid replacement — QLT
• X-Linked RP, DHA supplementation — Retina Foundation of the Southwest

Some Important Comments

This list doesn’t include every human study for a retinal degeneration. For example, there are four additional LCA-RPE65 gene therapy clinical trials that I didn’t include. There are several studies for age-related macular degeneration pharmaceuticals that are not on the list. I also didn’t include a few studies underway for artificial (a.k.a. “bionic”) retinas.

What is most impressive to me about the list is that nearly eight years ago, when I joined the Foundation, virtually none of these studies were underway. We’ve come a long way in that time. I expect this list to grow substantially in the next eight years, with some of the abovementioned emerging treatments gaining FDA approval.

Stay tuned and thanks for your interest in and/or support of sight-saving research.

That’s why I was pleased to recently learn that Oxford BioMedica’s StarGen™ gene therapy for Stargardt disease and RetinoStat® gene therapy for wet age-related macular degeneration received positive interim safety reviews from a Data and Safety Monitoring Board, an independent panel of science and medical experts, which monitors patient safety and treatment efficacy data for a clinical trial. The Foundation requires a DSMB for all its clinical trials, to ensure that no study participant is unnecessarily put in harm’s way.

After 12 months, eight patients in the Phase I/IIa StarGen clinical trial receiving the lowest dose (dose level 1) treatment have experienced no adverse events, and the DSMB supports treating four additional patients with a higher dose (dose level 2). If the safety profile of StarGen continues to be good, four additional patients will receive the highest dose (dose level 3).

In the Phase I RetinoStat clinical trial, a total of nine patients have been treated thus far with no adverse events. Three patients have been treated for each of three different dosing levels, with the first patients having received the dose level 1 treatment 18 months ago. In addition, the treatments are expressing the therapeutic proteins they were designed to express. The DSMB supports the treatment of nine additional patients in the RetinoStat trial.

The DSMB has not issued a safety review yet for the Phase I/II clinical trial of UshStat®, Oxford BioMedica’s gene therapy for Usher syndrome type 1B. That trial began in March 2012, so I wouldn’t expect a report until next year.

I know for those of you losing vision to retinal diseases, an announcement of safety for a treatment may not be the big news that you hope for, and that is perfectly understandable. You want your vision saved or restored. But please keep in mind that safety is the primary goal of these early-stage studies, and without safety, you have nothing.

Gene therapies, with as much promise as they hold, are still cutting-edge treatment approaches – which is why you can’t currently walk into a doctor’s office and ask for one. But our goal at the Foundation Fighting Blindness is to develop it to the point where your doctor says, “Gene therapy for your vision — no problem.” Safety is an essential step toward getting there.

“When the chip was turned on, at the very first second, I was able to see something in front of me,” the 47-year-old recalled recently. “But of course it was not clear yet. I only saw flashes.”

A few days passed, and Miikka (pronounced MEE-kah) was able to identify horizontal, vertical and slanted lines on a computer screen. Soon, he was seeing the outlines of geometric shapes, then of real objects – knives, forks and plates on a table, for example.

“Something was there, where I was looking,” he says. “I had not had that kind of feeling for years – that I’m turning my eye on something, and there’s something right there. That was a good moment.”

It’s a moment, in fact, captured on a BBC video included in a post written by our chief research officer, Dr. Steve Rose, back in April. But the moment didn’t last. In 2008, for just three months, Miikka, who has retinitis pigmentosa, or RP, was among the first participants in a clinical trial for a device developed by the German company Retina Implant AG.

“It’s a sub-retinal chip, placed below the retina,” Reinhard Rubow, one of the company’s co-founders explained to me. “The light coming into the lens of the eye is collected in that chip, then converted into electrical impulses,” which travel to the brain via the optical nerve.

The chip, in other words, replaces the eye’s photoreceptors, which are damaged, often severely, by retinal disease.

But the company’s device – the latest generation of which is now in clinical trials – is still a work-in-progress. Miikka knew, going in, that the device wouldn’t be implanted permanently, so that, even if it did work, he’d be back to using a cane eventually.

“To be honest, I don’t really care if I will see anymore,” he told me during VISIONS 2012, FFB’s annual conference, in Minneapolis. He was there, with Reinhard, to take part in a panel discussion on clinical-trial participation. “But this chip,” he added, “it’s just interesting stuff. I just want to play my small part in the research.”

This may be a concept difficult to grasp. But it makes sense to many, like Miikka, who’ve learned to live, even thrive, with vision loss, while wanting to help future generations avoid similar tribulations.

A resident of southern Finland, he was 16 when his RP was diagnosed, after he’d complained of night vision problems. Roughly 10 years later, he’d almost completely lost sight in his left eye and had to stop driving. By the year 2000, his right eye had failed him.

In the meantime, Miikka founded and ran a sports-management company, which he sold just last year, after he’d helped 1,000 European kids get athletic scholarships to American colleges. Still a member of the company’s board, he adheres to a strict workout regimen, which includes riding a tandem bicycle.

He’s a few inches under six feet, while Reinhard is well over that mark, which made for something of an odd couple as they navigated VISIONS 2012. Although he couldn’t see me during our interview between sessions, Miikka said that, if the implant were still in, I’d be something of a “shimmery, kind of a ghost-looking, shape. But I would not have been able to identify if you were a man or woman, necessarily, and not your face. But if you lift your arms, yes, I’d be able to see them right away.”

It was these kinds of descriptions that later had attendees at his session rapt with attention. He also told them that, given the chance, he’d jump at participating in another clinical trial for Retina Implant AG. He did, however, repeat what he’d already told me.

“I became involved because I’m interested in the science,” he said. “If I can get the final chip, no big deal. But if I can be part of its development, that’s everything.”

Pictured above: Reinhard Rubow (left) and Miikka Terho.

The grants review process began last fall when investigators from around the world submitted letters of intent (LOI) summarizing their proposed research. Their projects run the gamut, from gene therapy to stem cells to pharmaceuticals. Some efforts are directed at specific diseases, others are cross-cutting. We asked about one-third of those who submitted LOIs to send a full proposal, and those projects are what we’re reviewing now.

So what makes a good research project? There are a lot of factors, but, most important, it needs to be an effort that is scientifically sound and plays a role in the advancement of treatment and cures. We are willing to take some risks if the returns bring us closer to saving and restoring vision. As an example, back in the mid-1990s, gene therapy was considered risky, but now there are gene therapy clinical trials underway around the world, some of which are restoring vision.

Because there is so much great science available today, we can only fund a fraction of the high quality research efforts proposed to us. And while I can’t tell you exactly what the funding outcomes of the review process will be just yet, I do know that we would need somewhere in the neighborhood of an additional $4 million to fund all the projects we’d like to fund, and that’s just for the first year of these multi-year grants.

Well, I need to get back to doling out bread and water — I really am a nice guy at heart — but I look forward to reporting the results from the review process later this summer.

In the meantime, stay tuned for more science updates from VISIONS.

- Dr. Steve Rose

Pictured above: Dr. Eric Pierce, chairman of the SAB, and Amy Laster, FFB’s grants and awards program manager