Good news for hESC trials: transplanted human embryonic stem cell-derived retinal pigment epithelium… and it’s safe!

by Angela C.H. McDonald

As has been reported broadly this week, transplantation of human embryonic stem cell-derived retinal pigment epithelial cells appears to be safe in human patients, and it may even be efficacious (although this can only be confirmed via a Phase II trial). 

Advanced Cell Technology (of California) published a preliminary clinical report of their Phase I clinical trials online this Monday in the Lancet. The two Phase I clinical trials were initiated at UCLA’s Jules Stein Eye Institute in July 2011. These trials aimed to treat Stargardt’s Macular Dystrophy and Dry Age-Related Macular Degeneration (two major causes of blindness in the developed world). Each trial will enroll up to 12 patients, with a safety endpoint at 12 months. Four months following transplantation, no adverse affects such as tumorigenicity, ectopic tissue formation, inflammation or cell proliferation could be detected in patients.

The subretinal space of one eye in each patient was injected with retinal pigment epithelial cells generated from human embryonic stem cells. The retinal pigment epithelium is a single cell-thick protective layer in the eye. In the eye of a macular degeneration patient, retinal pigment epithelial cell degeneration causes dysfunction of photoreceptors (which sit on top of the retinal pigment epithelium) and vision in that area of the eye is lost.

Although visual acuity assessments revealed functional improvements in the transplanted eye of each patient, these results should be interpreted with caution. While the Stargardt’s Macular Dystrophy patient only showed improvement in the transplanted eye, the Dry Age-Related Macular Degeneration patient showed improved visual function in both. However, the injected eye did show more improvement than the non-treated eye.

Despite the fact that Monday’s report is very preliminary (results from only two patients at the four-month mark), the company must have a great deal of confidence in the trial for it to have made this public announcement. Additionally, Advanced Cell Technology announced in a press release published on their website Monday that patient enrollment has now begun in the UK for a Phase I clinical trial for Stargardt’s Macular Dystrophy and the first patient was treated in London last Friday.

This exciting news comes just two months after Geron’s announcement to end the first ever FDA-approved human embryonic stem cell Phase I clinical trial, a move described as a strategic financial decision by Geron (covered in a previous blog entry). Disappointment and controversy surrounded the sudden halt of the Geron trial and some question the motive behind this decision. Some speculate that a lack of efficacy in this safety trial is what lead Geron to pull the plug.

Although it felt like the stem cell community took a number of hits in 2011 (including the shut down of the Geron trial and the prohibition of patents for human embryonic stem cell products by the EU), it seems that 2012 is off to a great start. 

 

The “Viagra effect”: how known drugs can be repurposed to target cancer stem cells

by Paul Krzyzanowski

Repurposing known drugs for new applications is a strategy with fascinating potential, with two of the most notable examples being Thalidomide and Viagra. Thalidomide was commonly used in the late 1950s as a sedative in pregnant women, later being associated with serious birth defects. Today, it is used to treat multiple myeloma. Viagra was being developed by Pfizer to treat high blood pressure when its ability to ‘treat’ erectile dysfunction was identified as a side-effect, resulting in a complete shift in marketing strategy.

The major allure of finding novel uses for existing drugs is that the long process of early Phase I clinical trials can be sidestepped, as the drugs are already known to be safely delivered. This approach decreases the overall cost of developing drug candidates and brings the development of treatments for rare and neglected diseases closer to reality.

The principle of identifying a drug candidate is straightforward: take a large number of different chemical compounds and test each one for some desired activity. Small molecule screening has long been used by pharmaceutical companies to identify potential drug candidates for probably as many disease conditions as there’s a market for.

Trading on hope: A look at what motivates stem cell tourists and what happens when it goes wrong

In recent years, the research community has been quite outspoken in its condemnation of rogue stem cell clinics operating in many countries across the globe. Indeed, through announcements made by health and related ministries in China, India and the US, it appears the message is beginning to be heard.  

On the heels of a recent 60 Minutes newscast in the US, a similar exposé aired on January 14 here in Canada. In it, Stem Cell Network Scientific Director Michael Rudnicki spoke with Global TV’s Carolyn Jarvis, condemning stem cell tourism and the agencies that offer them as “despicable” (view the entire Global TV 16x9 segment here). His interview was just a small part of the broadcast, in which the news team looked at the unproven and unapproved therapies offered by a clinic operating in Mexico and a Canadian-based travel operator that offers packages to help people access the services.

Along with Rudnicki, the program profiles several patients, one of whom was successfully treated in an FDA-approved clinical trial for MS, another who was unsuccessfully treated in a Mexican clinic, and a set of parents raising funds to seek treatment in China for their five-year-old son. Each of the struggle to balance the pain of dealing with their ailments, the hope that stem cells could help them, and the risks involved in these experimental therapies.

Exercising caution over unproven therapies: India holds public consultation meetings to update stem cell guidelines

by David Kent

Last fall, I wrote on the Eurostemcell documentary film entitled Stem Cell Revolutions: A Vision of the Future, which featured some experimental stem cell treatments in India, and since that time, I have tried to keep my finger on the pulse of what has been happening in India with respect to stem cell therapy.

Last month a pair of interesting statements were made in the India Times:

“As of today there is no approved indication for stem cell therapy as part of routine medical practice, other than bone marrow transplantation.”

This was followed by:

Sifting through all that monkey business

by David Kent

 

Yesterday, a landmark paper emerged from Cell which reported two major findings to the scientific community:

1. Primate embryonic stem cells cannot generate chimeras, and 
2. Aggregation and injection of multiple early-stage four-cell primate embryos (not embryonic stem cells) can form chimeras. 

Together these findings underscore a fundamental difference between rodent and primate embryonic stem cell lines and show that generating primate chimeras is possible.

As you might expect, this article was heavily publicized (e.g.: The Guardian, The National Post, and the BBC) but it seems that all of the reports focus on the generation of a monkey chimera and not on the more challenging question for scientists that results from not being able to do this from embryonic stem cells. Much of our understanding about embryonic stem cells comes from studies in lower order animal models (frog, mouse, sheep, etc.) and scientists sometimes tacitly assume that this process operates similarly in humans. This not only has major implications for our understanding of early development, but also substantially impacts the struggle to bring stem cell derived therapies and treatments into the clinic.