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.

Stem Cells in Ophthalmology Update 24 Current Tables Now Online

My current stem cell/cell therapy tables are now online for anyone interested to access. Here is a brief description of what is available and how to access them:

Stem Cell/Cell Therapy Companies/Institutions Active in Ophthalmology

A list of forty-two companies and institutions working with stem cells/cell therapies for ophthalmic applications. The table lists collaborators, the cell type being used, and the applications for which the cells will be used.

Link: http://tinyurl.com/StemCellComp1231

Stem Cell/Cell Therapy in Ophthalmology by Application

A list of eighteen ophthalmic applications being studied and/or in clinical trials. The table includes the companies/institutions involved, the clinical trial status, and an active link for the clinical trial for those listed. (sixty-one active and completed clinical trials are shown.)

Link: http://tinyurl.com/StemCellAppl1231

Stem Cell/Cell Therapy in Ophthalmology -- Ongoing & Completed Clinical Trial Details

A list of the the eighteen ophthalmic applications and the sixty-one clinical trials showing the number of patients to be studied in each trial and the number studied to date (that I am aware of). Active links are provided for each ongoing or completed trial.

Link: http://tinyurl.com/StemCellClncl1230

Updated December 31, 2015. 

Stem Cells in Ophthalmology Update 15 Wills Eye Joins ACT’s Clinical Trials for Dry AMD Using Embryonic Stem Cell derived RPE

Advanced Cell Technology announced yesterday that the Wills Eye Institute in Philadelphia had received institutional review board (IRB) approval to become a site for the Phase I/II clinical trial for dry age-related macular degeneration (Dry AMD) using human embryonic stem cell (hESC)-derived retinal pigment epithelial (RPE) cells. Wills will join UCLA’s Jules Stein Eye Institute and Moorfields Eye Hospital in London as sites participating in the clinical trials for Dry AMD, under ACT’s National Clinical Trials protocols.

"The participation of Wills Eye Institute in this trial will significantly enhance our clinical program," said Robert Lanza, M.D., ACT's chief scientific officer. "Wills Eye Institute is the oldest eye-care facility in the United States and is consistently ranked as one of the best ophthalmology hospitals in the country by the U.S. News & World Report. We are looking forward to working with Dr. Regillo and his team to address the unmet medical needs of degenerative diseases of the retina. With this latest approval, the company continues to assemble a clinical team that includes the best eye hospitals and surgeons in the world in our effort to find an effective therapy for this devastating eye disease."

The Phase I/II trial for dry AMD is a prospective, open-label study designed to determine the safety and tolerability of the hESC-derived RPE cells following sub-retinal transplantation into patients with dry AMD. The trial will ultimately enroll 12 patients, with cohorts of three patients each in an ascending dosage format. Which patients will be enrolled at the Wills Eye Institute will be determined in the near future.

"Degenerative diseases of the retina often lead to a significant visual impairment," said Carl Regillo, M.D., director of clinical retina research at Wills Eye Institute and professor of ophthalmology at Thomas Jefferson University. "Replacing lost or damaged cells with functional and healthy cells may provide a treatment option that could slow vision loss, and perhaps even reverse the effects of disease. We are looking forward to collaborating with ACT to evaluate the potential of the stem cell-derived RPE cells for debilitating diseases such as Stargardt's macular dystrophy and dry AMD."

Dry AMD, or "central geographic atrophy," is the "dry" form of advanced age-related macular degeneration. Dry AMD occurs when the light-sensitive cells (photoreceptors) in the macula slowly break down, gradually blurring central vision in the affected eye. Over time, as less of the macula functions, central vision is gradually lost in the affected eye, often progressing to blindness. The loss of photoreceptors is a direct result of a preceding degeneration of the retinal pigment epithelial (RPE) layer of cells just below the retina. As many as 30 million people in the United States and Europe suffer from macular degeneration, which represents a $25-30 billion worldwide market that has yet to be effectively addressed. Approximately 10% of people ages 66 to 74 will have symptoms of macular degeneration, the vast majority suffering from the "dry" form of AMD -- which is currently untreatable. The prevalence increases to 30% in patients 75 to 85 years of age.

"We are honored to have the opportunity to work with one of the foremost eye care centers in the world", said Gary Rabin, chairman and chief executive officer of ACT. "This clinical trial represents the culmination of years of innovation and hard work by ACT's scientific team. The whole world is focused on our trials, most especially patients suffering from dry AMD and other forms of macular degeneration. Wills Eye Institute has a strong tradition of innovation and discovery, and we are excited at their participation in bringing this cutting-edge technology through the clinic."

Additional details about these studies, for which the Jules Stein Institute at the University of California, Los Angeles and Moorfields Eye Hospital in London have also received IRB approval, can be found at ClinicalTrials.gov Identifier: NCT01344993.

Editors Note: As noted in the above quote from Dr. Regillo, it can be speculated that Wills Eye will soon join both Jules Stein and Moorfields in also treating Stargardt’s disease, under ACT’s National Clinical Trials NCT01345006 and NCT01469832.

It should also be noted that Wills Eye is also one of the clinical sites participating in the Centecor (J&J) clinical study of Dry AMD using adult stem cells from umbilical cord blood, NTC01226628.

Breaking News – as of January 19th, Wills Eye had been added to ACT’s clinical protocol for treating Dry AMD with embryonic stem cell-derived RPE cells, and was actively recruiting patients.

About Wills Eye Institute

Wills Eye Institute is a global leader in ophthalmology, established in 1832 as the nation's first hospital specializing in eye care. U.S. News & World Report has consistently ranked Wills Eye as one of America's top three ophthalmology centers since the survey began in 1990. Wills Eye is a premier training site for all levels of medical education. Its resident and post-graduate training programs are among the most competitive in the country. One of the core strengths of Wills is the close connection between innovative research and advanced patient care. Wills provides the full range of primary and subspecialty eye care for improving and preserving sight, including cataract, cornea, retina, emergency care, glaucoma, neuro-ophthalmology, ocular oncology, oculoplastics, pathology, pediatric ophthalmology and ocular genetics, refractive surgery and retina. Ocular Services include the Wills Laser Correction Center, Low Vision Service, and Diagnostic Center. Its 24/7 Emergency Service is the only one of its kind in the region. Wills Eye also has a network of nine multi-specialty, ambulatory surgery centers throughout the tri-state area. To learn more, please visit www.willseye.org .

Gene Therapy in Ophthalmology Update 12 First Gene Therapy Approval on the Horizon

As Andrew Pollack writes in today’s NYTimes, “After more than two decades of dashed expectations, the field of gene therapy appears close to reaching a milestone: a regulatory approval. The European Medicines Agency has recommended approval of a gene therapy to treat a rare genetic disease.”

The therapy recommended for approval in Europe, called Glybera, was developed by uniQure, a Dutch company. It treats lipoprotein lipase deficiency, a disease that affects only several hundred people in the European Union and a similar number in North America.

People with the disease have a genetic mutation that prevents them from producing an enzyme needed to break down certain fat-carrying particles that circulate in the bloodstream after meals. Without the enzyme, so much fat can accumulate that the blood looks white rather than red.

Glybera provides correct copies of the lipoprotein lipase gene, which allows patients to make some of the needed enzyme. A single treatment, consisting of injections into multiple spots on the leg muscles on the same day, is expected to last for several years, if not longer, said Jörn Aldag, chief executive of uniQure.

The reason I believe that this is important is because it brings “legitimacy” to the whole field of regenerative medicine. As readers of this online Journal are aware, my interest is in the field of ophthalmology. As you may be further aware, I am currently tracking eleven clinical trials involving the use of stem cells to treat ophthalmic disorders and sixteen gene therapy clinical trials. Several of these are showing promising results and the above approval, when it comes, will bring increased attention to the whole of this field, including the ophthalmic trials.

Anyone interested in obtaining my latest tables of ongoing clinical trials in either or both areas, please use the “Email Me” link to the right to request copies.

Stem Cells in Ophthalmology Update 21 Clinical Trial Details

As with my inquiry into clinical trials underway using gene therapy in ophthalmology, Table 3 Gene Therapy in Ophthalmology - Ongoing Clinical Trial Details, I have undertaken a similar survey of the number of patients currently treated using stem cells. I found nine ongoing clinical trials and one about to begin.

As in the previous study, I visited the clinical trial information sites and extracted the pertinent information for use in this table, Table 3. Stem Cell Therapy in Ophthalmology - Ongoing Clinical Trial Details.

I then contacted each of the principals or sponsor involved in the study and requested the number of patients treated to date. The response to date has not been as good as with the gene therapy trials, but here is what I was able to find out.

Only two companies/institutions involved answered my request, and so I can only reliably report that 17 patients have been given stem cells for treatment of ophthalmic disorders to date.

I hope to gather additional information from either the clinical investigators or others and will update this table as new information is obtained.

Here, then, is the initial version of this table.

A downloadable pdf file of the above table is available by request.

To obtain copies of the current versions of the first two tables, listed below, please send me an email.

Table 1. Stem Cell Companies/Institutions Active in Ophthalmology

Table 2. Stem Cell Therapy in Ophthalmology by Application

Endoscopy in Ophthalmology The Latest News and Some History

I saw a brief writeup in the current OSN Supersite (September 22, 2009) about Endo Optiks launching a new series of high-resolution micro-endoscopes and it brought to mind the first time I learned and wrote about this company.

I first learned about video endoscopic techniques being used in ophthalmology in the Spring of 1991. At that year’s ASCRS Meeting I learned about Summit Technology’s OmniView and at the Fall AAO Meeting, about Escalon’s InnerView.. In the Summer of 1992, I learned about the newest technology in this field, to be introduced at that Fall’s AAO Meeting, the MicroProbe video endoscope from Endo Optiks. The story about these endoscopes was published in the October 15, 1992 issue of Ocular Surgery News.

I thought that some of you might be interested in both the latest news and a little bit of history.

Here is the latest news from Endo Optiks, followed by the original writeup published in October 1992.

Endo Optiks launches series of high-resolution micro-endoscopes

LITTLE SILVER, N.J. — Endo Optiks has added a new series of high-resolution micro-endoscopes to its existing endoscopes line, providing improved image quality and increased field of view, according to a press release from the company.

"We designed the new high-resolution scopes to help surgeons better visualize the anatomy of the eye," Martin Uram, MD, endoscope creator and co-founder of Endo Optiks, said in the release. "Surgeons will find improved visualization when performing endoscopic cyclophotocoagulation, panretinal photocoagulation and diagnostics."

Two new versions have been launched: the Triple Function Micro-Endoscope and the Dual Function Micro-Endoscope. Both combine light and imaging, but the Triple Function Micro-Endoscope model also offers laser, the release said. The Triple Function Micro-Endoscope has a 19-gauge probe, while the Dual Function Micro-Endoscope has a 20-gauge probe.

The high resolution of the devices is a 70% increase in pixels from the company's existing scopes, from the current 10,000 pixels to a 17,000 pixel fiber optic bundle, the release said.

In addition, the devices offer an expanded 160̊ field-of-view.

Source: OSN SuperSite 9/22/09


Original writeup as submitted July 17, 1992 to Ocular Surgery News and published in the October 15, 1992 issue:

Technology Update

MIS TECHNIQUES REACH OPHTHALMOLOGY

Irving J. Arons
Ophthalmic Consulting Group
Arthur D. Little

It was inevitable that video endoscopic techniques, now widely practiced in general laparoscopic/endoscopic surgery, should finally reach ophthalmology. True, most inner parts of the eye are readily viewed through the pupil and minimally invasive surgery has been a part of the ophthalmologist's armamentarium for some time, but certain parts of the eye are not easily viewed, much less treated, and this new technology seeks to correct this oversight. With the new technology, eye structures such as the back of the iris, the ciliary body, the far reaches of the retina, and sites at or near the zonule attachment points can now be clearly seen and treated. Further, with the magnification and visual detail available with today's video endoscopic equipment, enhanced views of cellular level structures are now possible for other areas of the eye as well.

Over the past two years, at least two video endoscopic techniques have been introduced into ophthalmology. At the 1991 ASCRS meeting, Summit Technology announced its OmniView, an ophthalmic fiberendoscopic system containing between 50 to 70 illuminating fibers surrounding an image guide, all bundled into an 0.8 mm probe. It was introduced for viewing of sutures placed into the ciliary body, for inspection of the integrity of the posterior capsule, and to verify IOL haptic placement. Other applications suggested were for viewing retinal and glaucoma surgery, for otolaryngology, lacrimal duct surgery and for neurosurgery. Summit expected to sell the system for about $18,000.

The second ophthalmic endoscopic system was InnerView, launched by Escalon Ophthalmics at last fall's AAO meeting. This again is a small (20 gauge, 0.9 mm) flexible endoscope probe that can be coupled to a high resolution video display. Although the price had not been fixed at the time of introduction last fall, it was estimated that the system would sell for between $16,000 to $18,000 complete.

However, the newest endoscopic technology, to be launched at this fall's Academy Meeting, is the MicroProbe, an integrated diode laser treatment device combined with a high resolution microendoscope. The new device is from Endo Optiks, a two-year old Little Silver, NJ startup company, founded by Dr Martin Uram, a retinal surgeon in New Jersey. Endo Optiks has been able to couple an endoscopic viewing system with a diode laser and is working on incorporation of an aspirator system, all into a 20 gauge (0.89 mm) probe that can both view and treat formerly inaccessible parts of the eye. Further, with its high resolution color capabilities, the system can be used for diagnosis of difficult to view intraocular structures.

The heart of the system is a unique, patented, lens delivery system that combines a high illumination light source, a high resolution video endoscopic pickup, and a 0.1 to 2 watt 810 nm diode laser photocoagulation delivery system, all contained within a 20 gauge probe. This will allow the surgeon to view and treat a variety of eye structures including the peripheral retina, the pars plana, ciliary body and the posterior aspects of the iris in vivo.

The MicroProbe consists of a compact console containing the light source, the high resolution video monitor, a VCR recorder, the aspirator pump, the diode laser (including a red diode aiming beam), and simple keyboard controls. The system has been undergoing clinical evaluation trials, has received 510 (k) marketing clearance, and will be officially launched at this years AAO Meeting (1992) in Dallas.

By integrating the viewing and treating modalities into a 20 guage handpiece, the new system is truly a breakthrough in ophthalmology. In addition to viewing and treating the peripheral retina and ciliary processes, the unique system can be used for up close and personal diagnoses of other eye structures, giving high resolution colored views of the retina, lens, iris, and other ocular structures (and implants).

The primary application for the new device is expected to be for retinal surgeons for performing all types of vitreoretinal procedures. However, it is expected that glaucoma specialists will also find use for the device in pursuing direct visualization and laser treatment of the ciliary processes, as an alternative treatment for intractable glaucoma. The technology holds great promise for use in other medical fields as well. It is anticipated that the MicroProbe integrated endoscopy and laser system will sell for between $50,000 to $60,000 when it comes to market this fall.

Stem Cells in Ophthalmology Update 3 ACT Files IND to Treat Dry AMD

Furthering its lead in stem cell research in ophthalmology, Advanced Cell Technology Inc., announced today that it  had filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration, to initiate a Phase I/II multicenter study for the  treatment of dry Age-Related Macular Degeneration (dry AMD) using human embryonic stem cell (hESC) derived retinal pigment epithelial (RPE) cells.

Dry AMD reportedly afflicts more than 30 million people worldwide, including an estimated13-15 million Americans. Approximately 10% of people 66 to 74 years of age will have findings of macular degeneration, and this prevalence increases to 30% in patients 75 to 85 years of age.

Dry AMD, or "central geographic atrophy," is the "dry" form of advanced Age-Related Macular Degeneration. Dry AMD occurs when the light-sensitive cells (photoreceptors) in the macula slowly break down, gradually blurring central vision in the affected eye. Over time, as less of the macula functions, central vision is gradually lost in the affected eye, often progressing to blindness. The loss of photoreceptors is a direct result of a preceding degeneration of the RPE layer of cells just below the retina. Dry AMD is much more common than wet AMD, which results from aberrant blood vessel formation in the eye. Some 85-90 percent of all people with intermediate and advanced AMD combined suffer from the dry form. Despite representing a $25-30 Billion market opportunity, there are currently no FDA-approved treatments for Dry AMD available.

The Phase I/II trial will be a prospective, open-label study that is designed to determine the safety and tolerability of the RPE cells following sub-retinal transplantation to patients with dry AMD. A total of 12 patients will be enrolled in the study at multiple clinical sites. The sites which are currently under consideration are the Jules Stein Eye Institute at UCLA; the Ophthalmology Department at Stanford University School of Medicine; and the Edward S. Harness Eye Institute at Columbia University College of Physicians and Surgeons; additional sites may be considered.

"We can generate a virtually unlimited supply of healthy RPE cells," said Robert Lanza, MD, ACT's Chief Scientific Officer. "In our animal studies, we observed significant improvement in visual performance over untreated animals, and did not find any adverse effects of the injection of RPE cells. In extending our studies to human patients, it is our hope that we will show that the injected RPE cells will rescue photoreceptors and slow, if not stop, the progression of macular degeneration."

On November 22, ACT announced that it had received FDA approval to begin treating patients as part of the company's Phase I/II Clinical Trial treat Stargardt's Disease, a form of juvenile macular degeneration. (See Stem Cells in Ophthalmology: Update 2) Company scientists view the use of the same hESC derived RPE cells for both trials as the most efficacious approach, as it permits the company to leverage its experience with the FDA that it gained through the process of obtaining approval for the Stargardt's clinical trial to expedite the approval of its clinical trial in Dry AMD.

"We are seeing the beginning of new era in medical treatment," continued Dr. Lanza. "The hope that stem cell therapies may one day repair and regenerate diseased organs and tissue goes far beyond what can be accomplished with traditional medicine. This approval shows an apparent readiness by the FDA to work with researchers to move exciting new stem cell based therapies out of the lab and into the clinic."

"Filing this IND represents the culmination of years of innovation and hard work by ACT's scientific team," said William M. Caldwell IV, Chairman and CEO of ACT. "With this second IND, and our plans to expand our studies in Europe, ACT is positioning itself as a true `translational' leader in the field of regenerative medicine. When you are the first, the whole world's eyes are on you, and in our case, most especially the eyes of the patients that suffer from AMD. We do not intend to let them down. We welcome this challenge, and of course plan to scale up our operations, as necessary, to continue to meet our milestones and help validate this technology platform."