2012-09-13

Co.Exist

The Company That Can Generate Medical Treatments From Embryonic Stem Cells Without Pissing Anyone Off

Stem cells manage to make everyone angry, but one company thinks it has found a way to reap the benefits without stirring up any issues.

Embryonic stem cells have been dubbed "the sleeper issue" of the 2012 election, but stem-cell research (taking cells from human embryos to create new cells that can treat disease) has long been a hot-button topic. The problem is that embryos traditionally are destroyed to extract the cells--something that plenty of people are uncomfortable with. But if there was a way to extract human embyronic stem cells without destroying anything, well, that shouldn’t create any ethical quandaries. Advanced Cell Technology, a biotechnology company specializing in cellular therapies, thinks it has the solution.

ACT uses an embryonic stem-cell-removal technique that doesn’t destroy anything: It removes a single cell from embryos that are in the eight-cell stage--in other words, extremely early on. It’s identical to what’s done in in-vitro fertilization clinic for genetic testing of diseases like Tay-Sachs and Huntington’s Disease. "It’s a non-destructive, non-harmful method of extracting these cells and creating embryonic stem cells. There are thousands of babies born every year having this exact kind of genetic testing done," says ACT CEO Gary Rabin.

Steven Schwartz, M.D., the study’s principal investigator and retina division chief at UCLA’s Jules Stein Eye, transplants the fully differentiated retinal pigment epithelial cells derived from human embryonic stem cells in a patient’s eye. Copyrights: Reed Hutchinson/ UCLA’s Jules Stein Eye Institute

The cells propagate infinitely, so once you have what you need, you never have to go back to an in-vitro fertilization clinic to get more. ACT hasn’t taken cells from a clinic since 2005.

The technique is just part of the battle, of course; creating viable medical treatments is also necessary to prove ACT’s worth. Despite a history of financial mismanagement--when Rabin joined the company in 2010, it had less than $1 million in the bank (now it has over $10 million)--ACT has some exciting developments coming down the pike.

Most of them have to with the eye, which is an ideal place to start for embryonic stem cell treatment: The subretinal space in the eye is immune-privileged, meaning there shouldn’t be any issues with immune system rejection; everything you do in the eye can be observed down to the cellular level thanks to advanced scanning techniques; and there are 15 million patients in the U.S. with age-related macular degeneration (AMD)--a number that is expected to double over the next 20 years as the population ages. There are no real cures or therapies for AMD, and most drugs used in the eye were developed in the 1960s. It’s a space that’s ripe for change.

ACT is running three phase 1 clinical trials: a U.S. trial of an AMD treatment, and two trials (one in the U.S. and one in the U.K.) with a treatment for Stargardt’s Macular Dystrophy (SMD), a juvenile disease that causes progressive vision loss, ultimately leading to blindness. The trials have been promising so far.

"All of the [11] patients [in the three trials] treated long enough to have any effect have had subjective improvements in visual acuity, and nearly all have had measurable improvement in visual acuity," says Rabin. "We didn’t expect that in this patient population. As this is a phase 1 study, we’re treating very late stage patients." The three trials are still ongoing, but ACT is on to thinking about how to design phase 2. "It’s clear now that we don’t have any safety issues with these cells," explains Rabin.

How do the stem cells get implanted in the first place? You start with an embryonic stem-cell line, and through culturing media and differentiation techniques turn them into retinal pigment epithelium (RPE)--cells that are critical for visual function. When RPE cells die because of old age or other causes, there’s a corresponding decline in vision. So ACT’s technique is to inject RPE cells into the back of the eye’s retinal space. "The cells are injected in a suspension of a proprietary media that’s more or less like a saline," says Rabin.

ACT’s main focus is on its eye treatments, but the company is also looking at the potential to use mesenchymal stem cells (MSCs), a kind of cell that can turn into a variety of cell types, to treat autoimmune disorders like multiple sclerosis and lupus. There are hundreds of clinical trials involving MSCs that are going on right now, but "the usefulness in earlier-stage cells give us a very significant advantage in terms of treating these kinds of diseases," says Rabin.

Right now, at least, ACT says it hasn’t experienced too much pushback for its methods. "The problem is in this political climate it’s a hot button issue. If you raise it with any Republican candidate, it’s 'Oh, you destroy embyronic stem cells, you’re killing babies.' It’s just a convenient headline," says Rabin. "There’s a lot of education we have to do to make people aware of how this [works]."

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4 Comments

  • Ira Pastor

    FYI -

    John Gurdon (a guy who based his career on frog egg research) and whose
    original cloning work was the basis for what Dr. Lanza studied for his
    breakthroughs, just got the Nobel.

    And as an FYI, we are developing
    proteins isolated from frog eggs (think Byetta, streptokinase, porcine
    insulin, Botox, etc.), not the eggs themselves or cells derived from
    them.

    Best,

    Ira

    http://blogs.nature.com/news/2...

  • Ira Pastor

    Alan, We're just a discovery stage company - don't need cGMP until we pull the trigger on the FDA program

  • Ira Pastor

    Interesting

    But there is one problem that is way bigger than
    the ethical issues and regulatory morass that obscure the whole stem
    cell space:

    In following the traditional reductionist drug
    development thinking of big pharma, no one in the stem cell research
    space (adult, embryonic, or otherwise) took the time to ask if cells
    would ever make good regenerative or repair therapeutic candidates.

    And at the end of the day, they may not.

    Contrary
    to popular belief, cells by themselves are NOT very regenerative in any
    way - cells can be "generative", when operating in a generative
    micro-environment, whereby an integrated group of cells executes on a
    generative development program - i.e. where a small group of cells
    grows, differentiates, interacts, and organizes as a group to form a
    final structure in a "bottom-up" process - where each step is dictated
    by genetic blueprints within our DNA, and each sequential step dictates
    the next step in the process via slight modifications to those stepwise
    genetic instructions.

    But that type of process, which builds
    flawless babies, as well as perfect new limbs and organs in the
    amphibian and invertebrate kingdoms (including hearts, brains, eyes,
    spinal cords, etc.) , is 180 degrees opposite from what the stem cell
    research infrastructure has been trying to achieve for a couple decades
    now - "top-down" regeneration, introducing millions of cells into a
    morphostatic micro-environment and hoping they miraculously become
    something.

     That's like throwing a few thousand bricks into my house and hoping that a new addition forms.

    Cells
    by themselves are quite oblivious to the organ that they will
    ultimately become part of - they know nothing about the final game plan -
    they just know their one step in the process and learn it from their
    closest cellular neighbors, and learn that step in a precisely timed
    sequence - and top down regeneration completely ignores this, and in
    doing so relegates issues like size control, positional identity,
    polarity etc., which are crucial for both proper structure and function,
    to the "back burner".

    And adult stem cells, which are always
    held in high regard (rightly so) for their history in bone marrow
    transplants and hematopoietic reconstitution, and promoted as the
    "body's repair system", in actuality do very little repair, for the most
    part dictated by our bodies micro-environments propensity to rapidly
    bleed and to bias for scar tissue recruitment versus alternatives.

    So
    while stem cells may have their place in the near future in certain
    niches, once inducible endogenous regeneration is perfected, they will
    most likely become obsolete in the long run.

    Ira S. Pastor
    CEO
    Bioquark Inc.
    www.bioquark.com

  • Alan Boitz

    Yes, ACT has it all wrong with their streamlined hESC program on its way to phII ahead of schedule...Im sure that bioquark will step right in and take the market by storm with their frog eggs, and without the use of a gmp facility. Stop trolling this company, please.