Asterias Update; Roman Recruits; Hans Spotted

Posted by Sam Maddox in Research News on July 22, 2016 # Research

Time to revisit Spawn of Geron, also known as the Asterias trial. This, as you recall, continues work to implant embryonic stem cells into newly injured spinal cords. Geron, a Bay Area biotech now trying to get a cancer medication going, gave the world the first ever FDA approved use of embryonic stem cells. The company plowed through the tedious regulatory pathways, and went on to dose five paraplegics. None got any obvious benefit but none showed adverse effects.

Geron famously ran out of money in 2011, and abandoned the trial, but former executives rescued the intellectual property and rebooted the trial two years ago. They got things going again, as Asterias, with the help of a $14.3 million grant from the California Institute of Regenerative Medicine (CIRM), the state stem cell agency. Here are some archive links on Asterias and the continuation of the trial.

Asterias uses the exact same cell line as implanted in the original patients, only now the company is upping the volume and dosing only cervical injuries; the first Geron group got 2 million oligodendrocyte precursor cells (AST-OPC1, embryonic cells that have been allowed to mature one step toward being oligodendrocytes, important support cells in the nervous system that keeping the nerve wiring intact and functional).

The most recently completed Asterias cohort (five patients) each got 10 million cells. They call it the SCiSTAR trial.

Ever wonder what the implanted cells are thought to be doing? Here’s what Asterias says, per press release:

AST-OPC1, an oligodendrocyte progenitor population derived from human embryonic stem cells, has been shown in animals or in vitro to have three potentially reparative functions that address the complex pathologies observed at the injury site of a spinal cord injury. These activities of AST-OPC1 include production of neurotrophic factors, stimulation of vascularization, and induction of remyelination of denuded axons, all of which are critical for the survival and regrowth of axons at the injury site, as well as for the conduction of nerve impulses through those axons. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hind limb and forelimb locomotor function, dramatic reductions in injury-related cavitation, and significant preservation of myelinated axons traversing the injury site.

30 Day Window

Trial protocols require that patients in SCiSTAR are motor and sensory complete quads; they get stem cells injected into their spinal cord between 14 and 30 days post injury. Asterias just got permission to boost enrollment in the cervical stem cell trial from 13 to 35 patients, and to expand the trial to include incomplete injuries. The next group will get double the dose, to 20 million cells (they hope to begin the next cohort this fall, pending safety review).

Dosing has been a key issue in the trial; many did not think the original cohort, at 2 million, got nearly enough cells to prove anything. But 20 million, the company says, is closer to the volume that falls “within the potentially efficacious range predicted from extensive preclinical studies.” In other words, the bigger dose comes with expectations that it might actually work.

The most recent Asterias implant took place earlier this month at Santa Clara Valley Medical Center. Jake Javier, 19, injured his cervical spinal cord in June, in a swimming pool mishap a day before his high school class was to graduate. Jake and his family, from East Bay, San Francisco, were encouraged to participate in the trial by Roman Reed, an SCI research advocate who lives a couple of towns away.

Reed and his dad Don are well-known in California. They convinced the state legislature to create the Roman Reed Spinal Cord Injury Research Program, which funded SCI research in the state from 2001-2011. The program was not renewed but the Roman Reed Core Laboratory at the Reeve-Irvine Research Center continues the legacy, with local funds.

According to UC Irvine, home of the Reeve-Irvine Center, the Reed grants have

“.... supported over 50 novel projects by California scientists. From embryonic stem cell therapies to emerging techniques to promote regeneration, the Roman Reed Program provided seed funding. Many of the seed grants led to large grants from the National Institutes of Health. About $15 million in state funding led to over $80 million in new grants, which greatly amplified research capacity and the pace of scientific discovery. It would be difficult to find a California spinal cord scientist who has not benefited from the program.”

Roman Reed is proud to note that the preclinical research for the Geron stem line came from the lab of Hans Kierstadt at UCI, funded in part by a Roman Reed grant.

Though Hans is still considered a stem cell rock star by Roman, and by many California cure advocates, he actually left the SCI field after selling his company California Stem Cell to a biotech called NeoStem. That company became Caladrius (a bird that visits the ill and absorbs illness before flying away) and concentrated on cancer therapies. Hans was chief science officer.

Hans, who posed for Men’s Vogue in 2006, sports a less flashy science profile now, but he’s still flying high, and apparently he hasn’t lost his knack for making rain. I ran into Hans at a function in Beverly Hills not long ago. He says he left Caladrius and has his own company again, named AiVita. The company, based in Irvine, just raised a round of venture capital money -- $2 million from California Technology Ventures – to pursue a cancer immunotherapy drug for ovarian cancer. A Phase II trial is set to enroll soon at Hoag Hospital in Newport Beach.

CIRM recently approved $4 million for AiVita to collaborate on early translational research for the development of stem cell-derived 3D-transplantable retinas to treat vision loss, in collaboration with Magdalene Seiler at UC Irvine.

AiVita is making money on its own with a stem cell product, but not in medicine. This is in the vanity business, with a facial serum stem-cell derived product called Provoque. Hans has published data showing that the serum, available to the “self pay” segment of health care at around $200 an ounce, reduces appearance of wrinkles. You can only buy this stuff from doctors at Alphaeon, a “healthcare lifestyle” company. Hans sits on the company’s board.

So Hans, any remaining spinal cord ambitions? Yes, indeed, he says has some ideas that he and his company hope to pursue, using profits from the skin care line to develop therapies addressing paralysis.