Wednesday, April 29, 2009

AMD Update 5: Emerging Technologies for Treating AMD

Over the past year and a half, I have been tracking several new technologies that have a good chance to become breakthrough technologies in the treatment of both wet and dry age-related macular degeneration (AMD). I have written about several of these (as shown below), and would like to introduce you to an exciting new approach, using embryonic stem cells, that looks like a winner.

First, a summary of some of the newer technologies that I have been tracking and writing about:

The Ellex 2RT Retina Regeneration Therapy

Just prior to the 2007 AAO meeting, I became aware of a new potential laser treatment for retinal diseases. I met with the then president of the company, Peter Falzone, and decided to write about what Professor John Marshall and his colleague Dr. Ali Hussain were proposing.

From what I understand, 2RT is the use of non-thermal laser pulses to “stimulate” the retinal pigment epithelial (RPE) cells. This in turn causes the RPE cells to migrate and release metalloproteinases, which are the enzymes that “clean” Bruch’s membrane. This, in turn increases the transport of water and chemicals through Bruchs to rejuvinate the retina.

For more on this, see my writeup: Ellex 2RT Retina Regeneration Therapy: A First Report

Collaboration Between Lumenis and Stemedica

In May of 2008, I became aware of the collaboration agreement between Lumenis and Stemedica, to use the Lumenis SRT laser to target RPE cells (similar to what John Marshall, above, was doing in London), and then to use Stemedica’s stem cell lines to regenerate the damaged retinal cells.

I contacted friends at Lumenis and the people at Stemedica, offering to write up what they were trying to do, and compare it with what John Marshall in London was doing.

Unfortunately, my friends at Lumenis were no longer with the company, and no-one at Stemedica was willing to talk to me.

Recently, a new-found friend at Lumenis informed me that the Lumenis SRT laser was no longer in the picture and that Stemedica was continuing on its own. I then got an offer from a researcher at Stemedica to tell me what they were doing, but upon followup, no further information was forthcoming. (I do know, however, that research on the project is continuing and being carried out at the Fyodorov Eye Institute in Russia.)

Also, one of my old friends from Lumenis, the former program manager, got in touch with me and said he was interested in pursuing the Lumenis SRT development project if he could obtain outside financing. So, this approach is still alive and ticking.

Visualization of Living RPE Cells

In February of this year, David Williams and his research group at the Institute of Optics at the University of Rochester announced that they had used adaptive optics to image RPE cells in vivo.

I have written up this announcement in more detail: AMD Update 4: Does Visualizing RPE Cells Hold the Key to Understanding AMD?

Now we have a diagnostic mechanism to see changes in RPE cells, possibly when applying some of the new techniques discussed above and below.

And, now, the breakthrough that could hold the key to finally finding a “cure” for AMD:

Embryonic Stem Cell Treatment for AMD

Finally, as noted above, I came across an article that appeared in the April 19, 2009 issue of the London Times Online, describing the work of Professor Peter Coffey of the London Project to Cure Blindness and Dr. Lyndon da Cruz, a surgeon at Moorfields Eye Hospital in London.

Their process involves replacing a layer of degenerated retinal cells with new ones, created from embryonic stem cells, pioneered by scientists and surgeons from the Institute of Ophthalmology at University College London and Moorfields Eye Hospital. Further, Pfizer has announced one of its new companies, Pfizer Regenerative Medicine, launched last year, will be providing financial backing of this project to bring the therapy to fruition. The undifferentiated embryonic stem cells will be transformed into differentiated replicas of the degenerated RPE cells, placed on a membrane and inserted into the back of the retina.

Professor Coffey believes that the insertion process could be accomplished in less than an hour, making this a potential outpatient process.

A clinical trial is expected to begin within two years and become the second in the world to use embryonic stem cells in humans. (The first being the work by Geron on patients with spinal cord injuries.)

This technology could become ground-breaking breakthrough technology in the treatment of dry AMD and Geographical Atrophy.

In their own words, here is how The London Project to Cure Blindness describes their process:

“Neuralised human embryonic stem cells (HESCs) represent a potentially unlimited source of progenitor cells for use in the repair of retinal disease. In addition to the genesis of retinal neurons, there is now compelling evidence that RPE can also be derived from undifferentiated HESCs. These ES-derived RPE cells not only appear to behave like normal RPE in culture but also have a gene expression profile more akin to primary human RPE. This is of particular clinical relevance to any RPE based transplantation strategies designed to treat AMD.”

“HESCs will be used to generate precursors of retinal pigment epithelium (RPE) cells in vitro in order to provide a candidate therapeutic for age related macular degeneration (ARMD). The previously used method will be optimized with respect to RPE cells to improve both yield and reproducibility. RPE transplantation has already been shown to be capable of restoring the subretinal anatomy and improving photoreceptor function in a variety of retinal diseases. The sourcing of appropriate cell lines with the prerequisite characteristics of RPE will allow transplantation to enter the mainstream of retinal therapy at a time when the treatment of previously blinding retinal diseases is finally becoming a reality.”

Pfizer Regenerative Medicine’s role will be to focus on clinical study design, product manufacturing (the membrane), and securing worldwide regulatory approvals.

Under the terms of the collaborative agreement, Pfizer will fund University College London's preclinical research. In turn, Pfizer will retain exclusive worldwide rights to proceed with efficacy trials to develop and commercialize any resulting retinal pigment epithelium stem cell-based therapies.

"We are excited to be working with pioneers in the field of stem cell ophthalmology from UCL," Ruth McKernan, PhD, chief scientific officer for Pfizer Regenerative Medicine, said. "While we have much to learn about how stem cells can be used therapeutically, we are confident that this relationship will increase that understanding and help us advance to a time when our work may benefit patients worldwide."

Wednesday, April 15, 2009

Vision Monday Columns: A Bit of Nostalgia

My first job as a columnist was for Vision Monday, a bi-weekly newspaper published (now) by the Jobson Group. As I recall, I joined VM upon when it first started, in September 1988. I intend to put some of the columns I wrote online, as I’m sure that Jobson does not have an archive going back to this time. This first online column, published either in February or March of 1989, relates my memories of the pioneers of the contact lens industry, and how I got my start in consulting, first in contact lenses, and then in the rest of ophthalmology.


Vision Monday,
March 1989

I recently saw a picture of Solon Braff, the founder of Calcon Labs, as he attended last Fall's International Society of Contact Lens Specialists biennial meeting (1988), and it brought back a flood of memories about my early days in consulting in the contact lens business.

Sol's Calcon Labs in Hollywood, CA was one of the first I toured along with the Soft Lenses operation in San Diego in 1976. That got me thinking about how I first got involved and of some of the entrepreneurs I have met along the way. The times certainly have changed. The contact lens industry has matured and few entrepreneurs remain in the business. Most companies today -- especially the larger ones -- are run by professional business people, most of whom have had little previous contact lens industry experience, as did their predecessors. But, ce est la vie, that’s the way it is, as we reach the 18th anniversary of the soft lens in the United States.

It all began for me when I joined Arthur D. Little in 1969. One of my first assignments was to try and find other uses besides contact lenses for HEMA, the polymer used in the first soft lenses. We had been retained by National Patent to find out what else could be done with this intriguing material that they had "discovered" in Czechoslovakia in the early 1960s. We didn't find much of value, but I began to keep files on this fascinating material that turned from hard plastic to soft with the addition of a small amount of water.

In early 1972, Joe Nemeth of Nemeth Contact Lens Lab in Boston, associated with the noted Boston ophthalmologist, Dr. Perry Rosenthal, visited ADL to see if he could use our laser to "fenestrate" (put holes in) contact lenses to increase their oxygen permeability. As one of the young plastic chemists on the staff, I was asked to meet with Joe, and then later with his associate, Dr. Rosenthal. Perry told me all about this new soft contact lens that he was working with, and how he wanted us to develop a new material that he could use to make contact lenses. I guess our development proposal was too costly; he eventually took the idea to the Univ. of Lowell, outside of Boston, started Polymer Technology and developed the Boston Lens.

In May 1972, I got a call from the underwriters working with National Patent on a proposed public offering. That began my longtime relationship with Jerry Feldman and Martin Pollak, the founders of National Patent. They hired ADL to conduct a worldwide inquiry into the safety of the then just released Bausch & Lomb Soflens, since nearly all their revenues were from royalties received from B&L. As part of that assignment, our ADL team interviewed all of the original clinical investigators of the B&L Soflens and I attended the Senate Select Hearings on Soft Lenses in July, 1972. I had the privilege of meeting and sitting next to Jim Dodd, then President of B&L's Soft Lens Division, and listening to Neal Bailey's testimony on the safety of the soft lens. After the meeting, I shared a taxi back to the airport with Bob Spriggs, the president of Automated Optics. Bob told me he was going to have the next soft lens approved and he was right. He had licensed the Seiderman physiological polymer (PhP) material to Don Brucker of Continous Curve, who's Soft Lenses' Hydrocurve Lens was the next cosmetic lens to win FDA approval in 1974.

As a result of that first assignment in 1972, I wrote and ADL published one of the first market research reports on the soft lens industry in 1973, and as they say, my career in the contact lens industry was established. Along the way I have met and interviewed many of the original industry pioneers, most of whom were introduced to me by my mentor, Neal Bailey, the original editor of Contact Lens Forum and now Contact Lens Spectrum. I would attend the CLMA and Optifair meetings and walk the exhibit halls with Neal who would introduce me to everyone who was someone in the industry.

Some of the more colorful pioneers have included Don Brucker of Continous Curve, who told me he couldn't talk to me because his company was in SEC registration (for a public offering) and then proceeded to spend a couple of hours telling me all about his hard and soft lens businesses. I had a similar experience with Orrin Stine, president of Wesley-Jessen, who told me in about two hours how he never gave interviews. Others included Stanley Gordon, president of UCO Optics, and his stories of the early days of the hard lens business; Fred Danker of Danker Labs and his compression molding lab on Long Island; and Alan Isen of Griffin Labs, who had sold his lens material to Warner Lambert (and its American Optical Division), and spent four hours in one of our conference rooms lecturing to me about the benefits of his Softcon material.

And there was Don Korb. Don and Miguel Refojo of the Retina Institute founded Corneal Sciences in Boston, and developed the CSI lens. They eventually sold CSI to Syntex and it now resides with Pilkington's Barnes-Hind. Don had fit one of the secretaries at ADL with his ultrathin CSI extended wear lens and when he found out where she worked, insisted that she not tell me anything about the lens. Of course I eventually found out about it and Don later became a friend and provided much insight into extended wear.

Of course I have to include Jerry Feldman and Martin Pollak in this group of entrepreneurs. They above all others were responsible, first, for the soft lens industry in the U.S., and for getting me started in this career. (Incidentally, those of you who are nostalgia buffs may be interested in getting a copy of Jerry's article, "The Hard Story of the Soft Contact Lens", that appeared in last September's Chemtech (1988), a magazine published by the American Chemical Society. It tells all about his and Martin's involvement in the beginnings of the soft lens.)

Well, finally, what goes around, comes around. I recently noticed that B&L was going to reintroduce the silicone elastomer lens into the market. Sol Braff's Calcon Labs was for a time owned by Dow Corning, who first introduced the silicone lens, "the lens of the future" (and it may always be -- but that’s another story), in the mid 1970s, and who then sold its rights to B&L. Next time I'll tell a little of the history of the silicone lens.