March 10, 2015

Using Tweaked, Implanted DNA, Harvard Team Successfully Treats Primate Parkinson’s Symptoms

According to an article published on March 3 in the Harvard Gazette, scientists have had success treating an ape’s Parkinson’s symptoms using the animal’s own genetic material.

The therapeutic process seems clear, but not simple. Researchers first took skin cells from the Parkinson’s-afflicted primate, then created stem cells (induced pluripotent stem cells, or iPS cells) from that tissue, then extracted dopamine-producing neurons from the stem cells, and finally implanted those neurons into the ape’s brain.

Beating the Tissue-Rejection Conundrum
Because those newly implanted neurons were produced from the ape’s own genetic material, there was no problem with tissue rejection. Earlier experiments had used dopamine-producing neurons harvested from embryonic stems cells. When those neurons were implanted, rejection became an issue, and the animals therefore required immunosuppressive drugs. As a result, the outcome was not especially positive.

Dr. Ole Isacson -- principal faculty member at the Harvard Stem Cell Institute, neurology professor at Harvard Medical School, and director of the Center for Neuroregeneration Research/ Neuroregeneration Laboratories at McLean Hospital – said, “It’s very difficult to get cell survival in primates. This is a very high bar to clear.”

After Surgery: As Agile as Any Ape
Those new neurons survived in the ape’s body for over two years, and dramatically reduced its PD-associated motor symptoms. After implantation, the animal could move around its cage as quickly as a healthy ape and showed normal agility.

According to Isacson, this particular experiment marked “the first time that an animal has recovered to the same activity level as before.”

As a kind of built-in control, Isacson’s team implanted the fresh dopamine-producing neurons into only one side of the animal’s brain. As they expected, motor improvements manifested only in the opposite side of the animal’s body. This “half a fix” explained why the disease continued to show some effect on the animal’s movements.

Next Up: Phase One Clinical Trial
Oleson and his team are eager to translate their success from primate to human, though he estimates it’ll be three years before they’re ready to apply with the FDA for a phase one clinical trial. That’s when researchers test a new drug – or, in this case, a treatment -- on a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.

In the interim, Isacson will focus on making cells contaminant-free, figuring the best way to grow cells that contain no animal proteins, and setting cell-freezing protocols which will enable his team to sort and store the cells. These steps will take time.

Let’s finish with a “reality check.” The study sample in this case is absurdly small – one lone ape. And the science required for this treatment is new and complex. Still, there’s a significant positive: the successful results which drive Isacson and his team forward are derived not from single-celled organisms, or even from mice. The achievement results from a successful genetic manipulation on a primate, with DNA remarkably like our own.  

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