The first speaker on the second day of the conference was Jonathan Thomas, chair of the Governing Board for the California Institute for Regenerative Medicine. This is the body that oversees $3 billion in stem cell funding created eight years ago by California voters. He said CIRM has the state at the “epicenter of stem cell research in the nation.” One could make the case that the state leads the world. He noted that 135 senior scientists moved their labs to California.
Thomas said $1.8 billion of the money has been spend; there are a dozen new science buildings (UC Santa Barbara just christened its Neuroscience Research Institute), and a cadre of trained people to do all the work. The money, from now on, is being directed toward clinical development and not so much for basic science. “We believe we are going to produce dramatic results,” Thomas said, referring to 38 diseases and conditions that are being targeted, including spinal cord injury.
CIRM recently awarded $20 million to StemCells, Inc. to fund preclinical studies on the company’s neural stem cell therapy, currently in a Phase I trial in Switzerland (I described this work last summer
. More on this below.)
Previously, CIRM had loaned $25 million to Geron for its first-ever embryonic stem cell trial, abruptly halted a year ago due to financial constraints. Only five people had gotten the Geron cells. (CIRM got the money back.) Thomas also acknowledged recent news reports that two former CEOs of Geron, Tom Okarma and Mike West, had made an offer to shareholders to acquire the abandoned stem cell portfolio and, presumably, bring the clinical trial back to life.
With impeccable timing, just as Thomas described how “extremely disappointing” it was for CIRM to see Geron quit its trial midstream, in rolled Katy Sharify – the fifth and final patient to get the Geron stem cell transplant (at Santa Clara Valley Medical Center in San Jose). Katy, 24, was that very morning marking the one-year anniversary of the car accident that paralyzed her. Later, I introduced her to Hans Keirstead, the Reeve-Irvine Center researcher whose basic stem cell science underpinned the Geron trial. He was thrilled to meet Katy and wondered, as anyone would, whether she had gotten any sort of benefit. The answer, said Katy, is no. Not yet, anyway.
Photo: Hans and Katy
(As an aside, Geron #1, TJ Atchison, was in the news lately. He is the namesake for a new SCI research core at the University of Alabama. The TJ Atchison Spinal Cord Injury Research Program got $400,000 initial funding from the state; the program was first modeled on the Roman Reed SCI research act in California, which was funded at $1 to $2 million a year from 2000 to 2010 from the state general fund. That money dried up; a recent attempt to fund it by way of traffic ticket surcharges passed the state legislature but was vetoed by Gov. Jerry Brown.)
Thomas was followed to the stage by Aileen Anderson, also from nearby Reeve-Irvine; her science (alongside her husband Brian Cummings -- no strangers in this space
) was the basis for the ongoing StemCells, Inc. trial at Balgrist University Hospital in Zurich. Anderson ran through the basic experiments she started 10 years ago to see what might become of human brain cells harvested from fetuses. They cultured these cells and then transplanted them in spinal cord injured animals, they survived, formed neuron support cells and indeed, stimulated recovery of function.
Anderson didn’t get into detail of the clinical trial. Stephen Huhn, a neurosurgeon who heads the program for StemCells, Inc., took over. Three people, ages 23, 45 and 53, got dosed in what’s called an early-chronic timeframe: three to 12 months post injury. (Anderson speculated that her stem cells might be effective in chronic injuries; her lab will get a big chunk of the CIRM $20 million to find out.). The first three patients are ASIA A, or complete injuries with no motor or sensory function below the lesion. Cell injections are made on the margins of the lesion. Treatment is accompanied by nine months of immunosuppression.
It’s been six months for the first batch of patients. None showed increase in pain. Two had gains in sensory function, measured by very sensitive heat and electrical perception devices. Said Huhn, “Something is happening biologically.”
The trial is still enrolling patients in Zurich. Said the company: “The second cohort will progress to patients classified as ASIA B, or patients with some degree of feeling below the injury. The third cohort will consist of patients classified as ASIA C, or patients with some degree of movement below the injury. In addition to assessing safety, the trial will evaluate preliminary efficacy using defined clinical endpoints, such as changes in sensation, motor, and bowel/bladder function.”
After lunch, Mark Tuszynski, Director of the Center for Neural Repair, University of California, San Diego. His talk, “Neural Stem Cells for Severe Spinal Cord Injury,” recapitulated recently published work
by Paul Lu in his lab showing robust growth “over extraordinary distances” axons from transplanted embryonic neural stem cells. Tuszynski said when Lu first approached him with the idea of using these cells, he was unimpressed. He tried to discourage it. But Lu may be on to something.
As noted in the paper published last summer:
"… early-stage neurons grafted in a fibrin matrix containing a growth factor cocktail extend large numbers of axons over long distances in the lesioned spinal cord and form neuronal relays that significantly improve electrophysiological and functional outcomes. The magnitude of functional effect substantially exceeds those previously reported in studies of fetal or stem cell grafts to the injured spinal cord…”
Tuszynski, whose stem cell science is also supported by CIRM, was clearly jazzed about this work. “It’s truly remarkable….I thought I would never see anything like this….to a scientist, to see this number of axons growing below the transection, it’s astonishing.” Next up for Lu and Tuszynski: larger animals and a chronic model.
Hans Keirstead was introduced with rock-star reverence (“world’s greatest stem cell scientist … most handsome … going to win Nobel Prize, a brother to me ….”) by the aforementioned cure champion Roman Reed (earlier awarded the United 2 Fight Paralysis “Kickass Advocate Award). Keirstead’s talk: “Stem-Cell Based Approaches to Treat Spinal Cord Injury.”
Keirstead described several active projects in his UCI lab, including the preclinical work leading to a human trial he thinks will get going in 2013. This study, sponsored by a company Keirstead is involved with called California Stem Cell, will test a motor neuron stem cell in young children with Type I spinal muscular atrophy. Sadly, this form of SMA is typically fatal to children, due to loss of respiratory function. The trial is based on animal studies
; the cells counteracted the disease process.
Keirstead was upbeat about recent work with PTEN gene deletion. He was also excited about using an animal’s own stem cells (induced pluripotent stem cells – iPSC) to “reprogram the astroglia scar.” This scar is believed to be a major barrier to axon recovery following SCI. What the iPSC cells do is drive old astrocytes cells in the scar into a younger, immature state. In this form, they are supportive of growth. “The old cells are tricked into thinking they are young.” It works in the dish. Keirstead expects to try it in an animal model of spinal cord injury.
W2W 2013: Boston.