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.

I was heartened to just learn that researchers from the Hadassah-Hebrew Medical Center in Jerusalem are receiving a $1.33 million grant from the Israeli government to advance their development of a stem cell treatment for people with dry age-related macular degeneration (AMD Hadassah is also funded by the Foundation Fighting Blindness. We are providing the group with a three-year, $300,000 grant for development of stem cell therapies.

Helping our researchers attract additional outside funding — whether from government entities or biopharmaceutical companies — is critical to the advancement of potential treatments and cures. In fact, I estimate that for every dollar we’ve invested in lab research, we’ve attracted seven dollars from the National Eye Institute. And in recent years, gene therapy development companies such as Oxford BioMedica and Applied Genetic Technologies Corporation are investing several millions in clinically focused research that was made possible by the Foundation’s funding of earlier lab studies.

Led by Dr. Benny Reubinoff, the Hadassah group is outstanding. I met with them earlier this year during my trip to Israel, and I was particularly impressed with their expertise in moving their research into human studies. They understand the regulatory challenges and technical rigors in advancing a potential therapy out of the lab and into the clinic. I am also impressed with Hadassah’s ambition; they are affiliated with companies that are targeting conditions like Parkinson’s disease and multiple sclerosis in addition to dry AMD.

I look forward to providing future updates on Hadassah’s progress toward a clinical trial of stem cells for dry AMD. So, stay tuned.

Pictured Above:  Dr. Benny Reubinoff.

• Dr. Matthew Vincent, Director of Corporate Development, Advanced Cell Technology (ACT). His company has clinical trials underway for a stem cell treatment for Stargardt disease and dry age-related macular degeneration.

• Dr. David Wilson, who is leading Oxford BioMedica’s StarGen (gene therapy for Stargardt disease) clinical trial at Oregon Health & Science University

• Dr. David Saperstein, representing QLT, Inc., which is conducting an international clinical trial of a drug for certain forms of retinitis pigmentosa (RP) and Leber congenital amaurosis (RPE65 and LRAT mutations)

Not only will they provide the latest updates on their human studies; they’ll also discuss how therapies will likely be used synergistically in the future.

For example, if you are a person with moderate to advanced RP, the ideal solution might be a gene therapy to halt the disease in your existing retinal cells coupled with stem cells to replace the rods and cones you’ve lost.

Or consider this example: Let’s say you have RP and are taking vitamin A to slow the progress of vision loss and a drug becomes available that also slows vision loss. Does that mean you stop taking vitamin A? Maybe not — it depends on if and how the new treatment and vitamin A can work together. (By the way, Dr. Eliot Berson will talk about vitamin A, lutein, and oily fish at the 3:45 p.m. session on Friday, June 30.)

A third example: We are getting closer to the day when your skin or blood may be your own source of stem cells. That magic is done through a process called inducing pluripotent stem cells, and gene therapy may be used to correct the genetic defect so the cells are disease-free when they are put into your retina.

Of course, combination therapies are a ways off, but this closing session will underscore why it is important to consider multiple treatments and not just one approach to saving your vision. I am sure the discussions will be lively and informative.

So, I hope to see you in Minneapolis. If you’re planning to go, make sure you stick around for the grand finale on Sunday.

Dr. Robert MacLaren

I was very excited to learn here at ARVO that two early-stage gene therapy clinical trials – one for choroideremia taking place in the U.K., the other for autosomal recessive retinitis pigmentosa (arRP) caused by MERTK mutations underway in Saudi Arabia – are proceeding well thus far. It is important to keep in mind that safety is the primary focus in these Phase I studies.

Dr. Emad Abboud, from the King Khaled Eye Specialist Hospital in Riyadh, reported that three patients, all in their thirties, have been treated with the MERTK gene therapy. The treatment uses an adeno-associated virus 2 (AAV2) – similar to the AAV2 used in landmark vision-restoring gene therapy clinical trials for Leber congenital amaurosis – to deliver copies of the therapeutic gene to retinal pigment epithelial cells in the retina.

Thus far, the MERTK treatment has been safe in all three patients. The two patients who received the treatment in 2011 have reported that they are seeing better with their treated eye and can read more lines on an eye chart than they could before the treatment. One woman said, “I see with the operated eye many things in the kitchen that I couldn’t see before.” The third patient, treated in April 2012, has not had his vision tested since receiving the therapy.

This study is being performed in collaboration with Dr. Kang Zhang at the University of California, San Diego.

Dr. Robert MacLaren, who is conducting the choroideremia gene therapy clinical trial at Moorfields Eye Hospital in London and Oxford Eye Hospital in Oxford, said that six people have been treated thus far with no adverse effects. This therapy also uses an AAV2 to get copies of the healthy gene into the retinal cells.

Dr. MacLaren notes that all six patients entered the trial with relatively good vision, and the goal is to demonstrate that the treatment prevents vision loss. He estimates that it will take at least two years to determine if the patients’ treated retinas have less degeneration, and better vision, than their untreated retinas.

We need to keep in mind that these are very early results for just a handful of patients. Cautious optimism is in order. Not every treatment that enters a clinical trial will be a home run. But the progress is exciting, and we couldn’t have a better group of researchers on the front lines working to get these treatments out to the people who need them.

By the way, the Foundation funded critical lab studies that made both the choroideremia and MERTK gene therapy clinical trials possible.

Now imagine that, sometime in adolescence or young adulthood, you notice you’re also having trouble with your vision. Maybe you bump into things more than you used to, or have trouble seeing in the dark. At first, you might think you just need glasses. But after a visit to the eye doctor, you discover you’re losing your vision to retinitis pigmentosa (RP).

This is often the sequence of events for people who have Usher syndrome, a genetic condition that leads to both hearing and vision loss. It’s the world’s leading cause of combined blindness and deafness, affecting as many as 400,000 people. While all retinal diseases are difficult, the one-two punch of Usher syndrome can be especially devastating. So halting and reversing its resulting vision loss is an important part of the Foundation’s mission.

That’s why I’m very excited to report that our partner Oxford BioMedica announced today the start of a clinical trial at Oregon Health & Science University for a gene therapy to treat Usher syndrome type 1B. Dr. Richard Weleber is leading the charge, and an article on the Foundation’s website provides details about the study and the condition.

Known as UshStat, the gene therapy is the first vision treatment specifically for Usher syndrome to move into a clinical, or human, trial. FFB funded years of lab research that made the study possible. I should also note that many of the RP projects and emerging treatments we fund — such as the drug TUDCA, which shows promise for preserving vision — may end up helping people with Usher syndrome.

The primary goal of the first phase of the UshStat trial is to evaluate safety, but Dr. Weleber and his team will also be looking at the treatment’s effect on vision. We’ll be sure to report initial results of the study as soon as we learn them.

People often ask me why Usher syndrome affects both hearing and vision. It all comes down to tiny tube-like structures called cilia, which work like a transport system, or conveyor belt, within retinal and inner-ear cells. Cilia move critical proteins and nutrients through the cells, a process that is necessary for their health and functioning. Usher syndrome is caused by genetic defects that ultimately lead to a breakdown in this transportation system, and, subsequently, hearing and vision are lost.

Defects in cilia-related genes are often a cause of other retinal diseases, such as RP and Leber congenital amaurosis, so they are, and will remain, an important area of research for us.