Wednesday, September 26, 2012

Progress Being Made In Treating Eye Diseases Using Regenerative Medicine

Over the past two years, I have written extensively about the human clinical trials underway for treating eye diseases using both stem cells and gene therapy. There are currently eighteen clinical trials using stem cells and sixteen trials using gene therapy to treat about a dozen different eye diseases. At latest count, at least as I have been able to determine, nearly 80 patients have had gene therapy treatments and more than two-dozen have had stem cell treatments. The initial results of many of these trials will probably be discussed at the upcoming American Academy of Ophthalmology Meeting to be held in Chicago in mid-November of this year.

Gene Therapy Trials

The most advanced of these studies are those underway at Children’s Hospital of Philadelphia, where doctors have administered gene therapy treatments to more than 16 patients suffering from Leber’s Congenital Amaurosis (LCA), some having received the therapy in their second eye after successful treatment of their first eye.

Leber’s is a rare form of inherited blindness caused by retinal degenerative disease that strikes in infancy and causes sever loss of vision. It is an autosomal recessive disorder that affects both the rods and cones. In the first completed trial, the light sensitivity of all 12 partially blind patients improved. Four of the children gained enough vision to play sports and stop using learning aids at school.

Other clinical trials are aimed at the wet form of age-related macular degeneration (which, if not halted leads to blindness), choroideremia (a rare inherited disorder that causes progressive loss of vision due to degeneration of the choroid and retina), Stargardt’s disease (an inherited juvenile macular degeneration that causes progressive vision loss), and Usher’s Syndrome (a relatively rare genetic disorder that is a leading cause of deaf blindness). In addition to Children's Hospital, Oxford BioMedica has several clinical studies underway

Stem Cell Trials

Advanced Cell Technology is at the forefront of the use of stem cells to treat ocular diseases. The company is sponsoring three clinical trials to treat Stargardt’s disease (one trial each in the United States and one in the United Kingdom) and one clinical trial to treat the dry form of age-related macular degeneration in the U.S. To date, four patients have received retinal pigment epithelial (RPE) cells derived from human embryonic stem cells for the dry AMD, and seven patients have been treated with RPE cells in both the Stargardt’s trials. Early results indicate improved vision in all of the treated patients and, detailed results are expected to be presented in November at the AAO Meeting in Chicago.

Other clinical trials underway include those aimed at treating corneal surface defects, corneal epithelial cell deficiencies, and treatment of optic nerve atrophy. In addition to the eleven patients being treated in the ACT trials noted above, an additional fourteen patients, at least, have received stem cell treatments.

To read more about what I have written on both stem cells (more than 20 articles) and gene therapy (16 articles), see the links referenced below.

To obtain copies of my current tables listing all of the clinical trials underway, including the number of patients treated to date in each trial, please send me an email request.


A List of Writeups on Stem Cells Used in Ophthalmology

A List of Writeups on Gene Therapy Used in Ophthalmology

Saturday, September 15, 2012

Menu 20: A List of Writeups on Stem Cells Used in Ophthalmology

I realized that I’ve put posted more than 20 articles on the subject of using stem cells in ophthalmology, and thought interested readers might like to see a compilation in one place, with links to the full writeups, so here it is.

Menu 21 is a similar list with all of my gene therapy in ophthalmology articles.

Stem Cells

The what, who, and why of stem cells in ophthalmology.
What stem cells are all about, who’s involved, and what diseases of the eye are being treated.

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.

Advanced Cell Technology’s request to begin treating patients with Stargardt’s disease was approved by the FDA. This will be the second trial using human embryonic stem cells. The first being granted to Geron to treat spinal disease.

A multi-center trial will involve twelve patients. If the results are positive, ACT anticipates filing for an IND to treat age-related macular degeneration, as well as filing to begin clinical trials in Europe in the very near future.

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.

Advanced Cell Technology Inc., announced today that it  had received approval from the FDA to commence its clinical trial using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs) to treat the dry form of age-related macular degeneration. ACT is now permitted to initiate a Phase I/II multicenter clinical trial to treat patients with dry AMD, the most common form of macular degeneration in the world. There are currently no approved treatments available for this prevalent disease of an aging global population. Dry AMD, representing a substantial global market opportunity and afflicts between 10-15 million Americans, and a further 10 million Europeans.

As the senior editor, John Gever, of MedPage Today reported, following the publication of three studies about induced pluripotent stem cells in the March 3rd, issue of Nature, “The road to regenerative medicine based on induced pluripotent stem cells (iPSCs) may have developed a giant pothole, with new studies showing that the cells are prone to several types of genetic defects.”

A safety study on the use of  stem cells in the eye, in a clinical study underway at the Fyodorov Federal Institution of Eye Microsurgery in Moscow, to treat diabetic retinopathy and diabetic optical neuropathy with stem cells derived from bone marrow, has been accepted for presentation as a poster at the upcoming ARVO (2011) Annual Meeting in Fort Lauderdale at the beginning of May. An abstract is shown below.

Two research studies were published this week, about the use of induced pluripotent stem cells (iPSCs) in treating retinal problems, but with opposing results.

Advanced Cell Technology announced today that it had enrolled the first patients in its two Phase I/II clinical trials, using retinal pigment epithelial (RPE) cells derived from embryonic stem cells (hESCs) for treating Stargardt’s Macular Dystropyy (SMD) and for the treatment of the dry form of age-related macular degeneration (Dry AMD). The first of twelve patients in each trial were enrolled at the Jules Stein Eye Institute at the University of California, Los Angeles (UCLA).

As I reported back on June 16th, Advanced Cell Technology had enrolled the first two patients in its Phase I/II clinical trials using retinal pigment epithelial (RPE) cells derived from embryonic stem cells (hESCs) for treating Stargardt’s Macular Dystrophy (SMD) and for the treatment of the dry form of age-related macular degeneration (Dry AMD). The company announced today that these first patients had now successfully received their first dose of the stem cells.

In a news announcement today, Advanced Cell Technology said it had received approval to expand its stem cell treatment for Stargardt’s Macular Dystrophy to Moorfield’s Hospital in the UK.

The story of Centecor (now Janssen)/J&J’s program to deliver stem cells to the macular in the hopes of treating geographic atrophy in dry AMD.

Stem Cells in Ophthalmology Update 12: Updated Table of Company Participants

This table is now out-date. See the offer for up-to-date tables at the end of this menu.

In the wake of the 60 Minutes expose of illegitimate stem cell activities, I thought I would bring you good news about a couple of  legitimate, government approved clinical trials using stem cells.

Stem Cells in Ophthalmology Update 14: Current Stem Cell Clinical Trials

Again, this table is also out-of-date – see the offer below for the latest tables.

The announcement that Wills Eye had joined the clinical trials.

The four press releases from ACT while I was on vacation.

Stem Cells in Ophthalmology Update 18: StemCells Inc. Demonstrates That its Human Neural Stem Cells Preserve Vision – Gets FDA Authorization to Initiate Clinical Trial for Dry AMD

On January 30, 2012, StemCells Inc. announced the publication of preclinical data demonstrating that its proprietary HuCNS-SCr cells (purified human neural stem cells) protect host photoreceptors and preserve vision in an animal model of retinal disease. The preclinical results are highly relevant to human disorders of vision loss, the most notable of which is dry age-related macular degeneration (AMD). The study is available online at and will be featured as the cover article in the February issue of the international peer-reviewed European Journal of Neuroscience.

Stem Cells in Ophthalmology Update 19: ACT Adds Bascom Palmer as Another Clinical Site for Dry AMD Trials

Advanced Cell Technology said that Bascom Palmer Eye Institute had received IRB approval to become the third U.S. clinical site for testing ACT’s human embryonic stem cell-derived retinal pigment epithelial cells in the treatment of dry age-related macular degeneration. Bascom Palmer, one of the country’s premier eye institutes, joins UCLA’s Jules Stein Eye Institute and the Wills Eye Institute as the third U.S. site participating in the clinical trials.

Stem Cells in Ophthalmology Update 20: ACT Adds Mass Eye & Ear as Fourth Clinical Site for Dry AMD Trials

Advanced Cell Technology announced that Mass Eye & Ear Infirmary had received IRB approval to become the fourth clinical site for ACT’s embryonic stem cell trials in treating the dry form of age-related macular degeneration.

Harvard’s Mass Eye & Ear joins UCLA’s/Jules Stein, Wills Eye Institute, and Bascom Palmer in the ongoing Phase I/II clinical trial using subretinal injections of embryonic stem cell-derived retinal pigment epithelial cells.

In addition, it is my understanding that Moorfields Eye Hospital in London is awaiting final approval of an IND application to also participate in ACT’s clinical trial for dry AMD, along with its current participation as part of the company’s Stargardt’s disease stem cell clinical trial.

Stem Cells in Ophthalmology Update 21: Clinical Trial Details

In attempting to determine how many patients have been treated with stem cells for eye disorders, I quickly found that no one was keeping track – at least no one that I could find.

So, I decided to try and get this data. I have now obtained partial data for three of the 9 clinical trials underway and present this information in my new table.

Again, to obtain the latest version of this table, please request it via email.

Stem Cells in Ophthalmology Update 22: A Stargardt’s Clinical Trial Patient’s Story – In Her Own Words

Maurie Hill, a young woman with Stargardt’s disease was accepted into Advanced Cell Technology’s embryonic stem cell clinical trial. She was the first person to receive 100K of RPE cells derived from human embryonic stem cells.

In this blog post she describes her experiences.

And, finally, the blog entry on how to obtain the current, up-to-date tables of both stem cell companies and clinical trials underway, and the same for gene therapy companies and trials.

Because I have been updating this information almost on a daily basis, I’ve decided to no longer post the information on this Journal (Irv Arons’ Journal), as it is practically out-of-date almost as soon as I post it. Therefore, I will only offer my tables of information to those who are interested in receiving them, and request them via email. I usually put notices on the appropriate LinkedIn Forums and on my Twitter feed (see sidebar) when there is substantial new information to report.

Here is what is currently available:

Stem Cells

Stem Cell Companies (and Institutions) Active in Ophthalmology

A list of snineteen companies and institutions working with stem cells for ophthalmic applications. The table lists collaborators, the cell type being used, and the applications against which the cells will be applied.

Stem Cell Therapy in Ophthalmology by Applications

A list of six ophthalmic applications being tested in clinical trials. The table includes which companies/institutions are involved, the clinical trial status, and the clinical trial number for those which are currently active. (Eleven active clinical trials are listed, with live links.)

Stem Cell Therapy in Ophthalmology -- Ongoing Clinical Trials 

A list of the the six ophthalmic application and the eleven clinical trials showing the number of patients to be treated in each clinical trial and the number treated to date (that I am aware of).

Gene Therapy

Gene Therapy Companies/Institutions Active in Ophthalmology

The table lists more than twenty-five companies and institutions actively pursuing gene therapy solutions to ophthalmic diseases. The table shows the delivery viral platform, the gene type being used (where known), the application, and clinical status.

Gene Therapy in Ophthalmology by Application

This table, like the one for stem cells, lists the ophthalmic indication, the company/institutions involved, the clinical status, and the clinical trial number. (Fifteen active clinical trials are listed, with live links.)

Gene Therapy in Ophthalmology -- Ongoing Clinical Trial Details

Again, as with the stem cell clinical trial table, this table lists all of the active clinical trials, the number of patients to be treated and the number of patients treated to date.

Anyone interested in receiving a copy of any or all of the above tables, please contact me via email (see the link in the side bar) and let me know which ones, or all four, that you wish to obtain. The tables are in pdf format, and as mentioned, contain live links to all of the clinical trials listed.

Irv Arons

Saturday, September 08, 2012

AMD Update 21: Good News for Patients With Stargardt’s Disease

Stargardt’s disease (also known as Stargardt macular dystrophy) is the most common form of inherited juvenile macular degeneration. Inherited as an autosomal recessive trait, it is a severe form of macular degeneration that begins in late childhood, leading to legal blindness. Stargardt’s disease is symptomatically similar to age-related macular degeneration, and it affects approximately one in 10,000 children.

There are currently two approaches underway to treat Stargardt’s, the use of embryonic stem cells to produce retinal pigmented epithelial (RPE) cells, which are injected subretinally, to replace damaged RPE cells (which take care of the photoreceptor cells) (sponsored by Advanced Cell Technology), and the use of gene therapy, to replace mutations in the ABCA4 gene, which cause Stargardt’s disease, and produces a dysfunctional protein (RPE) that cannot perform its transport function. As a result, photoreceptor cells degenerate, and vision loss occurs (sponsored by Oxford BioMedica).

A few days ago, the Foundation Fighting Blindness announced a new program to 1) study people with Stargardt’s to gain information about how best to treat it, 2) to better understand the disease’s progression, and 3) to identify potential patients for future clinical trials.

Here is how FFB described their ProgStar program, an important step in understanding and treating Stargardt’s disease.

Sept. 4, 2012 - The Foundation Fighting Blindness Clinical Research Institute is launching a natural history study of people affected by Stargardt disease. Known as ProgStar, the study has three primary goals: 1) determine the best outcome measures to accelerate evaluation of emerging treatments; 2) better understand disease progression for selecting future clinical trial participants; and 3) identify potential participants for forthcoming clinical trials.

The study, taking place in multiple locations worldwide, will combine both prospective and retrospective analyses. The prospective portion, for which physicians will track the progression of disease in participants, will last at least a year, with a possible one-year extension. Physicians will also retrospectively analyze disease progression by reviewing participants' past medical records. 

"Stargardt disease has a complex effect on the retina," says Dr. Hendrik Scholl, of the Wilmer Eye Institute, Johns Hopkins Hospital, ProgStar's protocol principal investigator and study director. "Also the rate of disease progression can vary between people and is difficult to measure. These issues can make selection of clinical trial outcome measures and participants challenging. But ProgStar will help us design better human studies of potential treatments and increase our chances of success."

During ProgStar, researchers will evaluate a number of outcome measures, including retinal images, visual fields and visual acuity.

ProgStar is preparing to enroll its first participants in early 2013. The study's clinician-scientists, listed below, will recruit as many as 300 patients from their practices. No additional recruitment will be conducted, and ProgStar will not involve administration of potential therapies.

Principal investigators for the study are:

    Dr. Paul Bernstein, University of Utah (Salt Lake City)
    Dr. David Birch, Retina Foundation of the Southwest (Dallas)
    Dr. Gerald Fishman, The Chicago Lighthouse (Chicago)
    Dr. Samuel Jacobson, University of Pennsylvania (Philadelphia)
   Dr. Michel Michaelides, Moorfields Eye Hospital (London, United Kingdom)
    Dr. José Sahel, Institut de la Vision (Paris, France)
    Dr. Hendrik Scholl, Johns Hopkins Hospital (Baltimore)
    Dr. Janet Sunness, Greater Baltimore Medical Center (Baltimore)
    Dr. Eberhart Zrenner, University of Tübingen (Tübingen, Germany)

Participants for the study are being recruited only from the existing patient populations of the nine principal investigators listed above. People who are not existing patients of one of these physicians are not eligible for the study.

Participating in study design are Drs. Frederick Ferris and Brian Brooks, of the National Eye Institute, Dr. Johanna Seddon, of Tufts Medical Center, and Dr. Richard Weleber, of Oregon Health & Science University.

Dr. Srinivas Sadda, of the Doheny Eye Institute, University of Southern California, will be analyzing imaging and visual field data collected from the study centers.