Usher syndrome type 1 occurs if any of these proteins are missing or defective. However, normal mice have neither the girdle nor the abundance of Usher 1 proteins in that region of their photoreceptors, making them an inadequate model of human Usher 1 disease.

Traditionally, testing emerging therapies in animal models has been an important first step before evaluating them in humans. As the Usher 1 mouse illustrates, animal models have their limitations.

The answer to this problem, as the French researchers note, may be induced pluripotent stem cells (iPSC). Scientists have found a way to take a small skin or blood sample from a patient, turn back the clock on those sample cells so they become stem cells, and then coax them forward to become photoreceptors, or any other cell type in the body. And voila! — we have a model of human retinal disease that we can study in a dish. We can even use the new cells to test drugs and gene therapies.

Keep in mind that iPSC won’t be a complete replacement for an animal model; we still need a complete biological system for testing safety. But human iPSC greatly improve our ability to understand disease and test potential therapies.

What’s even more exciting is that researchers are using induced pluripotent stem calls to make new photoreceptors and other retinal cells, which can be transplanted back into the patient to replace those cells lost to retinal disease.

The therapeutic potential for iPSC is so big, a Japanese researcher just won a Nobel Prize for discovering them.

Above: detail image of a retina, with photoreceptors in green.

I’d be remiss if I didn’t mention that Michelle is under the care of Dr. Richard Weleber, the study’s principal investigator, an outstanding clinician-researcher and one of the most pleasant, unassuming people I know.

It will likely take several months — perhaps years — to know if the UshStat treatment is working. The treatment’s primary goal is to halt or slow the progress of vision loss, which can occur slowly in patients with Usher syndrome and related retinal conditions. So, we need to be patient awaiting results on efficacy. But I am optimistic about the treatment’s potential for saving vision.

In case you missed it, I also blogged recently about an emerging Usher 2A gene therapy, and there are two recent articles focused on Usher syndrome on the Foundation’s website. One’s about expansion of the UshStat trial in Paris, France; the other about the discovery of a new Usher gene.

But I wanted to highlight a particular effort that addresses an important need in gene therapy for retinal degenerations: Delivering large corrective genes to cells in the retina.

For those of you who’ve seen the original “Jaws,” the summer blockbuster movie of 1975 about a killer shark terrorizing beachgoers, you may remember one dramatic scene. After he sees the enormous shark up close for the first time, Police Chief Brody, played by Roy Scheider, declares, “We’re gonna need a bigger boat.”

That’s the kind of situation we find ourselves in with diseases like Usher syndrome 2A (USH2A), LCA caused by defects in the CEP290 gene and RP caused by defects in EYS. We need a “bigger boat” to deliver healthy versions of these and other large genes to the retina. While current viral gene delivery systems, such as adeno-associated viruses and lentiviruses, are working well in clinical trials for retinal disease, they aren’t able to carry very large genes.

That’s where the nanoparticle-based gene therapy research being conducted by Dr. Muna Naash at Oklahoma University Health Sciences Center comes in. Nanoparticles are like tiny manmade rocks that are 1/12,000th the diameter of a human hair. Scientists can wrap just about any sized gene in them. Dr. Naash has shown that nanoparticles, with their therapeutic genetic cargo, are readily absorbed by retinal cells after being injected into the eye.

As part of this latest round of funding, we are supporting her development of a treatment for USH2A, but Dr. Nash’s emerging technology could be used to deliver large corrective genes for a variety of retinal diseases. So, we are excited about the potential for her treatment to help a lot of people.

Now, if you happen to be going to the beach soon, remember to wear sunglasses, sunscreen and a wide-brimmed hat – to protect your skin and your eyes. While they make for fun cinema, shark attacks are the least of your beachgoing worries, especially if “swimming” means you only go up to your ankles, like me.

Illustrated above: nanoparticles (courtesy of the National Institutes of Health)

Such is the case with The Wall Street Journal, which, among other FFB associates, quotes our chief research officer, Dr. Steve Rose, in this article, focusing specifically on Stargardt disease. It’s accompanied by a blog post that gives a shout-out to Eye on the Cure while confirming the Foundation’s position as a leader in research-funding efforts.

It’s also worth noting that the WSJ article includes mention of a gene therapy developed, and being tested in a clinical trial, by the British company Oxford BioMedica. Known as StarGen, it’s one of a few of the company’s treatments-in-development that FFB has had a hand in funding. That includes a gene therapy for Usher syndrome which is undergoing a clinical trial in both the United States and France.

Thank you, Wall Street Journal, for getting the word out! Otherwise, visitors to Eye on the Cure can rely on our continual reports on research developments for various retinal diseases.

Interestingly, I learned from listening to the families that a number of affected children were of Chinese descent and had been adopted as infants. Because these children were profoundly deaf when adopted, and are now losing their vision very quickly, it appears to me that they have Usher syndrome type 1, the most severe form.

I happen to be going to China in August where I’ll meet with retinal specialists, including Dr. Ruifang Sui, of the Beijing Eye Hospital, who is the recipient of an FFB Career Development Award.  I am very interested to learn about the prevalence of Usher syndrome in China, and the other inherited rare retinal degenerative diseases in the Chinese populations.

What we learn, clinically and genetically, about Usher syndrome and other retinal diseases in China may be of great benefit to those affected in the West — and vice versa. The more affected people we can identify and study, the better we can understand the diseases and how to overcome them.

In presenting research updates to attendees of the Usher Family Conference, I was joined by Dr. William Kimberling, of Boys Town in Omaha, Nebraska, and the University of Iowa, and Dr. Margaret Kenna, of Harvard Medical School. Together, we informed the families about advances in understanding the genetics and molecular basis of both the retinal degeneration (Dr. Kimberling) and hearing loss (Dr. Kenna) in Usher syndrome.

I addition, I discussed advances in gene therapy, including the UshStat® gene therapy clinical trial for Usher 1B underway and enrolling patients at Oregon Health & Science University. I also told the group about very promising emerging drugs for Usher 1C — and potentially other forms of Usher syndrome and retinal diseases — which read through genetic mistakes. Researchers are currently using the Usher 1C mouse model to test these potential therapies before they are studied in humans.

My presentation included an overview of an emerging nanoparticle-based gene therapy for Usher syndrome 2A (USH2A). A key advantage of nanoparticles is that they can carry larger genes, like the USH2A gene, which viral-based gene delivery systems can’t deliver.

While adeno-associated viruses (AAVs) and Oxford BioMedica’s lentiviral systems are performing well in clinical trials and labs, they are limited in their delivery capacity. So nanoparticles are an important area of research for the Foundation and our members.

Stay tuned for additional reports from my “European Tour,” which includes stops in Amsterdam, Germany and France. It isn’t exactly a rock-and-roll tour, but if it was, I guess I’d call my band “Genes and Roses.”

Love,
Axl

Pictured above: At the Foundation’s recent VISIONS 2012 conference, a tactile interpreter translates a lecture for a man affected by both vision and hearing loss.