Company Builds on FFB’s Initial Investment to Garner $265 Million in Therapy Development Funding
In the early 1990s, scientists began discovering the genetic defects causing blinding, inherited retinal diseases and saw a unique opportunity to overcome them. They envisioned gene therapy — delivering healthy genes to the retina to replace the bad ones — as an elegant approach to saving and restoring vision. Furthermore, a single injection of gene therapy would likely halt or reverse the disease process and work effectively for several years, perhaps the patients’ lifetimes.
The Foundation Fighting Blindness, the world’s leading private, nonprofit retinal research organization, funded most of these genetic discoveries for retinal diseases and immediately recognized the enormous opportunity for gene therapy to beat blindness.
Sometimes, fighting blindness means helping people save the vision they have, or at least slowing disease progression enough so they can maintain useful vision for all of their lives.
That’s the idea behind a promising, emerging drug for retinitis pigmentosa (RP) known as N-acetylcysteine-amide (NACA). The Foundation Fighting Blindness Clinical Research Institute (FFB-CRI) has announced an investment of up to $7.5 million to advance the potential therapy into and through a Phase II clinical trial. In several animal models, including previous FFB-funded lab studies of rodent models at Johns Hopkins University, NACA slowed retinal degeneration.
No, people with inherited retinal diseases don’t have to adopt new names or personas, or go into witness protection programs, to save their vision. But by changing the identity of cells in the retina — namely rods — researchers may someday be able to slow or halt vision loss for those with retinitis pigmentosa (RP) and other related conditions.
While the innovative therapeutic approach is not ready to be tested in humans, a research team led by Tom Reh, PhD, University of Washington, and Sheng Ding, PhD, University of California, San Francisco, accomplished the feat in mice with RP. The investigators treated rods in the mice with a compound known as photoregulin1 (PR1) that blocked a gene involved in rod development called Nr2e3. That, in turn, reduced the expression (activity) of other rod-associated genes, making the rods less rod-like and more like cones. Doing so stopped retinal degeneration, preserving both rods and cones. Rods and cones are important, because they’re the cells that make vision possible. Results of the PR1 study were published online in the journal Investigative Ophthalmology & Visual Science.
The Foundation Fighting Blindness annual report, released this week, details another groundbreaking year in which Foundation-funded studies made great strides across the continuum of research that will one day cure blindness caused by retinal degenerative disease. That work included harnessing the power of gene and stem-cell therapies, partnering with pharmaceutical companies to develop new drug treatments, and working across the retinal science community to create clinical trial endpoints that will strengthen and speed the all-important clinical trials process.
You can read the full report at:
In simple terms, genes are like recipes for making proteins. All the cells in our bodies “read” genetic information so they can make the critical proteins necessary to stay healthy and function properly. If there is a mistake in a gene — that is, a misspelling — a protein might not be made correctly and cells in the retina might degenerate and cause vision loss.
These misspellings are called mutations, and just like a mistake in a recipe, some mutations are more devastating than others. For example, when baking a cake, let’s say there is an error in the recipe. It incorrectly calls for a quarter cup of sugar, when the right amount is a half of a cup. The cake may not taste great, but it is still edible. But let’s say the instruction for adding flour is omitted entirely. Then the cake will be a complete failure and go uneaten.
An image of an electrically connected patch of one single class of retinal neurons that signal brightness for the visual system. Each single cell is shaped like a spider or octopus and connected to its neighbors. This is the first visualization of such a population of cells that has been untangled from the complete connectome.
In simple terms, the retina is a thin, delicate layer of tissue lining the back of the eye that captures light like film or digital sensors in a camera. But the retina is actually an incredibly complex network of hundreds of millions cells that process light, converting it into electronic signals, which are sent to the brain and used to create the images we see. And, understanding the pathways of this gargantuan network — and how they are rewired with aging and disease — is helpful in trying to save and restore vision.
“If you are going to fix cells in the retina, you have to know how they communicate,” said Robert E. Marc, Ph.D., University of Utah, in the opening keynote lecture at the RD2016 meeting in Kyoto, Japan. Held September 19-24, RD2016 is the largest research conference dedicated exclusively to retinal degenerations, and funded in part by the Foundation Fighting Blindness.
Inherited retinal diseases are difficult to understand merely because they’re so rare and diverse. More than 250 genes, when mutated, can cause them, yet collectively, they affect only 200,000 people in the United States.
Their widely varying impact on vision adds to the challenge. For example, the youngest sibling in a family may be nearly blind from retinitis pigmentosa (RP), while his or her older brother or sister with the same RP gene mutation can have near normal vision.
But as FFB-funded retinal geneticist Stephen Daiger, Ph.D., discussed at the RD2016 meeting in Kyoto, Japan, the complex and elusive nature of these conditions can also extend to the way they are passed down in families, making diagnosis and prognosis quite challenging. Dr. Daiger was one of nearly 300 retinal researchers who gathered September 19-24, 2016, for the world’s largest conference focused exclusively on retinal degenerative diseases. The conference was supported in-part by FFB.
William Beltran, Artur Cideciyan, Gustavo Aguirre and Samuel Jacobson. Photo by John Donges/Penn Vet
When scientists embark on developing a treatment for an inherited retinal disease, one of their first tasks is to identify or create a model of the condition. Disease models can be cells in a Petri dish, a genetically engineered mouse or rat, or larger animal such as a pig. Each type of model has its pros and cons, including cost and similarity of disease characteristics to those in humans.
The investigators then use the model to study how vision is lost — that is, they figure out which types of retinal cells degenerate, what is causing the degeneration, and how quickly the cells stop working. After they gain an understanding of the disease, researchers evaluate potential therapeutic approaches using the model as a testing platform.
The goal: Move a therapy into a human study.