Recently in Ophthalmology Category
At last, something positive (albeit very preliminary) to report about the use of human embryonic stem cells (hESCs)...in disease, no less.Yesterday The Lancet published (and made freely available—!) early safety results from Advanced Cell Technology's 2 prospective phase 1/2 clinical studies of hESC-derived retinal pigment epithelium in 2 blind patients, one with dry age-related macular degeneration and the other with a much rarer, genetic equivalent, Stargardt's disease. Both diseases result from the degeneration of the RPE, which leads to photoreceptor loss, and the former condition is the leading cause of blindness in the developed world.*
During the 4 months after subretinal transplantation of RPE cells, the investigators confirmed structural attachment and no evidence of hyperproliferation, other signs of abnormal growth, or rejection in either patient. In addition, the patients reported very modest improvements in vision from baseline; although a placebo effect in these cases is probably very strong. Most important, however, is that neither patient described a deterioration in vision.
The authors conclude that the "future therapeutic goal will be to treat patients earlier in the disease processes, potentially increasing the likelihood of photoreceptor and central visual rescue." The estimated enrollment for each of the ongoing studies is 12.
The share price of ACT's penny stock has risen considerably since early January, from 7 cents to 18 cents (a 150% jump), and the rise began weeks before the publication of yesterday's cautiously favorable article—a phenomenon that suggests some insider knowledge or buzz. On January 5th, the company announced that its chairman and CEO, Gary Rabin, would be presenting at the EBD Group's Biotech Showcase, and specifically at the Regenerative Medicine State of the Industry Briefing workshop on January 10th. Reason suggests that Rabin mentioned something concrete at the workshop to maintain an already growing interest in ACT.
* For leading causes of blindness in the world, go here.Graphic of retina with evidence of AMD from an NIH web page.
01/25/12 addendum: According to an astute ophthalmologist, it should be noted that patients in these hESC transplantation studies require immunosuppression to reduce the risk of graft rejection, namely in the form of tacrolimus (eg, Prograf) and mycophenylate mofetil (eg, CellCept). Although it's been previously reported that hESC transplantation may be more feasible in the eye, because the environment is relatively immune privileged, this is only really true for the cornea and natural lens of the eye, which lack blood vessels. The retina and the underlying choroid are highly vascular; consequently immunosuppression is a must with the subretinal grafting of hESC RPE cells. Autologous retinal grafts (which appear to be in an even earlier stage of development) would preclude the need for immunosuppressants. This recent review describes the current status of using stem cells for the treatment of retinal diseases.
By way of Nature Medicine's blog, A Spoonful of Medicine:Now 4 clinical trials with human embryonic stem cells (hESCs) have been launched; although 3 of these trials are from the same company (Advanced Cell Technology [ACT]) with the same hESCs (retinal pigment cells) for similar diseases (Stardgardt's disease, an inherited form of macular degeneration, and dry age-related macular degeneration [AMD]).
Here's the timeline (derived, in part, from a previous post):
1. In July 2010, the FDA lifted its regulatory hold* on Geron's clinical trial program for hESC-derived oligodendrocytes in subacute spinal-cord injury. The company announced this week that it has now enrolled 4 patients in the study. The "landmark" trial was featured in last week's SF Chronicle. The first unidentified enrollee was profiled by the Washington Post in April.
2. In November 2010, the FDA approved ACT's first trial of retinal pigment cells in patients with Stardgardt's disease (which affects only about 30,000 Americans but is an important disease model for dry AMD—which is much, much more prevalent). The first enrollee was treated in July at UCLA.
3. In January 2011, the FDA gave another nod to ACT to begin its hESC trial in patients with dry AMD. The first enrollee was treated in July at UCLA.
4. The UK Medicine and Healthcare products Regulatory Agency just gave approval to ACT to also conduct a trial of its retinal pigment cells in patients with Stargardt's disease at Moorfields Eye Hospital in London.
The Nature blog adds that ACT is in "late-stage talks" with other global regulators to conduct similar trials elsewhere around the world. News of these advances in clinical development of hESC treatment appears to have already been built into both companies' share prices—which are in the penny range.
* The hold was originally placed owing to preclinical concerns about the development of epithelial cysts at the site of injury.
Transverse section of the thoracic spinal cord from Gray's Anatomy (1918).
