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Research in Retinal Disease The Foundation Fighting Blindness Invests 2 1 Million in Seven New Research Efforts

As I continually search the web for interesting news about new technologies for treating retinal diseases, I came across this news from the Foundation Fighting Blindness’ website  yesterday afternoon. It relates to some of the annual grants to researchers that the FFB will be funding this year. It includes better ways of looking at retinal cells (via use of the adaptive optics laser scanning ophthalmoscope) and several projects involving gene therapy, along with a couple looking at ways of, hopefully, stopping the progression of dry AMD.

The following write up is reprinted with permission of the FFB.

The Foundation Invests $2.1 Million in Seven New Research Efforts

The Foundation Fighting Blindness

August 15, 2013

The Foundation's Scientific Advisory Board (SAB) recently completed its annual grants review process, leading to the allocation of $2.1 million in funding for seven new research projects, including those for identifying new disease-causing gene mutations, developing cross-cutting gene therapies and advancing potential treatments for dry age-related macular degeneration. The three-year grants were awarded after the SAB reviewed 117 proposals submitted to the Foundation last October.

"Grants review is a rigorous, multi-step process that takes most of the year to complete," says Stephen Rose, Ph.D., chief research officer, Foundation Fighting Blindness. "Due to revenue limitations, we can only fund a fraction of the high-quality projects we'd like to fund. That makes the selection process even more challenging. We had to leave several excellent proposals on the table."

Here are brief descriptions of the new research projects:

AOSLO: Detecting Retinal Degeneration Before Vision is Lost

The adaptive optics laser scanning ophthalmoscope (AOSLO) is like a powerful microscope that enables retinal researchers to see structural changes in the retina well before vision is lost from a retinal disease. That power can enable researchers to more quickly determine if a treatment is working in a clinical trial. Austin Roorda, Ph.D., of the University of California, Berkeley, is performing studies of AOSLO to correlate changes in the retina (e.g., loss of photoreceptors) with changes in vision.

Enhancing AOSLO for Expanded Clinical Use

Like Dr. Roorda, Stephen Burns, Ph.D., of the University of Indiana, is working with AOSLO to study the correlation between retinal and vision changes. He is also making AOSLO more affordable by using newer camera technology. In addition, he's employing state-of-the-art computing technologies derived from video games to decrease image-processing times and costs. The new technology will make the imaging process more comfortable for the patient by tolerating more head and eye movement.

Figuring Out Why Severity of Vision Loss Varies for People with XLRP

Researchers have reported for many years that the severity of vision loss for people with X-linked retinitis pigmentosa (XLRP) can vary greatly, even for people within the same family. Stephen Daiger, Ph.D., of the University of Texas Health Science Center at Houston, will be looking at the role of a various biological, genetic and environmental factors in vision-loss variability for those with XLRP. The identification of a significant factor that modulates vision-loss severity - perhaps a protective protein - could lead to a potential treatment.

Finding New Genes Linked to ADRP

Researchers have identified almost two dozen genes linked to autosomal dominant retinitis pigmentosa (adRP), but many are yet to be found. Rui Chen, Ph.D., of Baylor College of Medicine, is on the hunt for those remaining adRP genes. With DNA from 118 adRP families, including 18 families with at least nine affected members, Dr. Chen is well positioned to identify additional genes linked to adRP. Finding the new genes will provide researchers with targets for treatments and cures.

Developing Neuroprotective Gene Therapies to Preserve Vision

John Ash, Ph.D., is developing gene therapies that have the potential to preserve vision in people affected by a broad range of retinal diseases. Unlike corrective gene therapies, which work only for conditions caused by a specific gene, Dr. Ash's proposed treatments are designed to keep the retina healthy independent of the underlying disease-causing gene. He also believes the proteins delivered by his treatments - PIM-1 and STAT3 - will be less likely to cause damaging inflammatory side effects than some previously investigated neuroprotective proteins.

Targeting Inflammation to Halt AMD

Thanks to previous Foundation-funded genetic studies, researchers have strong evidence that the progression of age-related macular degeneration is associated with an over-active immune system. This ultimately leads to inflammation and cell death in the retinal pigment epithelium (RPE), a layer of cells that provides critical waste and nutritional support to photoreceptors. Loss of the RPE subsequently leads to loss of photoreceptors and vision. Jayakrishna Ambati, M.D., of the University of Kentucky, is developing a gene therapy that preserves the RPE by preventing the harmful sequence of immune-system events.

Boosting Cells' Energy Supplies to Save Vision in AMD

Based on prior research, Deborah Ferrington, M.D., of the University of Minnesota, believes that mitochondrial dysfunction in the RPE plays a significant role in the development of AMD. Mitochondria are like miniature organs (organelles) within all cells that provide energy. When not working properly in retinal cells, they can lead to cell death and vision loss. Dr. Ferrington is evaluating compounds that help protect mitochondrial function in the RPE.

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Stem Cells in Ophthalmology An Update AstraZeneca Joins the Fray

As reported by The Guardian (UK), AstraZeneca and University College London (UCL) have announced a research partnership, to develop medicines that use stem cells to repair damaged eyesight in people with diabetes.

Under the three-year partnership, funded by the drugmaker, researchers from AstraZeneca will team up with scientists at the UCL Institute of Ophthalmology to work on new medicines that use the regenerative capacity of stem cells. They hope to come up with a compound in three to five years, which could then undergo clinical development and possibly be on the market in 10 years' time.

Dr Marcus Fruttiger of the UCL Institute of Ophthalmology, who is leading the project, said: "These tools could be used either to manufacture transplantable material or to directly stimulate new cell growth in the eye to help restore or improve the vision of those with diabetic retinopathy (DR)."

AstraZeneca's U.S. rival Pfizer also has a partnership with Professor Pete Coffey of the UCL Institute of Ophthalmology, aimed at another eye condition, macular degeneration. Coffey said: "It's great that 'Big Pharma' is considering regenerative medicines as a serious possibility." He added: "This is British science being developed into a commercial entity with the pharmaceutical industry. It's a good example why the government shouldn't cut funding for biomedical research."

While this is the first time that AstraZeneca has worked on medicine for retinopathy, diabetes has been an area of focus. The company has a new diabetes treatment on the market called Onglyza, which was developed with Bristol-Myers Squibb, and the companies are developing a second diabetes drug that could be submitted to regulators for approval later this year.

Diabetic retinopathy (DR) is now the most common cause of vision impairment or blindness among western people of working age.

* The majority of patients with type-1 diabetes, which occurs when the body produces no insulin and often develops during the teenage years, will suffer eyesight problems and about 20%-30% will become blind;

* Moreover, at least 50% of patients with type-2 diabetes - the far more common type of diabetes, which occurs when the body produces too little insulin or when cells in the body do not react properly to insulin - will also develop retinopathy over time;

* With the rapid spread of type-2 diabetes, which is linked to obesity, the need for a retinopathy treatment will grow as more than 438 M people are expected to suffer from diabetes by 2030;

* A study published this year by Oxford University predicted that eight out of 10 men and almost 7 to 10 women will be overweight or obese by 2020;

* It forecast a 98% rise in obesity-related diabetes by 2050.

About AstraZeneca

AstraZeneca is a global, innovation-driven biopharmaceutical business with a primary focus on the discovery, development and commercialisation of prescription medicines. As a leader in gastrointestinal, cardiovascular, neuroscience, respiratory and inflammation, oncology and infectious disease medicines, AstraZeneca generated global revenues of US $32.8 billion in 2009. For more information please visit: www.astrazeneca.com

To read about the other companies involved in developing stem cells for use in ophthalmology, along with an extensive description of what stem cells are all about, and where they are being used in ophthalmology, please see: A Primer on the Use of Stem Cells in Ophthalmology.

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