ATLANTA – A new era for stem cell research could lie ahead in the U.S., thanks to President Barack Obama's lifting of the ban on stem cell research and the subsequent FDA decision allowing Geron Corp. to begin the first embryonic stem cell-based clinical trial in the U.S.
But this good news may have to be taken with a large grain of salt.
Instead of a talk on cell fate in stem cells, one talk at the recent BIO International Convention here focused more on the fate of stem cell research. According to Steve Burrill, CEO of Burrill & Company, "Most everything we are talking about doing is still being done in the academic world." Public expectation of what stem cells can do in the clinic has gotten ahead of reality, he said. "The public has never been as engaged in anything."
He added, "The regulatory world, all over the world, is very unsettled about what stem cell therapies are or should be."
Some countries are more permissive than others and clinical use of stem cells is often not based on rigorous, evidence-based science. In the U.S., "pharmacovigilance trumps approval," said Burrill. "That will be a barrier," he added. The U.S. "will then be a late adaptor" compared to other nations. Given that stem cell research is in the early, high-risk stage, Burrill said, "It's an unlikely place for VCs to invest," although "the VCs as a whole, like stem cells."
Rich Gregory, senior vice president and head of research at Genzyme (Cambridge, Massachusetts), said, "I believe the well-controlled system is good." However, anything that could accelerate product development would help increase investor interest, he said. He said he believes stem cells "will probably remain a cottage industry for a long time," adding "The industrialization of that process is what I think will take years."
In a recent Marks & Clerk (London) survey of international biotech executives, there was widespread belief that the Obama stem cell policy reform would improve the regenerative playing field for the U.S.; however, 40% also believed there is significant risk of further biotech failures, particularly companies in early development.
Lamentably, most stem cell companies fall into this category. According to Genzyme, there currently are about 100 stem cell companies, globally. Although few in number, their influence on the future of healthcare may be incalculable.
Stem cells have already had a tremendous impact. Although human stem cells were first isolated in 1998, they have been used in humans for decades longer. At another BIO session, Andrew Balber of Duke University (Durham, North Carolina), said, "Bone marrow transplant is the father of stem cell therapy," since it has been around for 50 years, and use of umbilical cord blood for 21 years. Genzyme has had the autologous chondrocyte therapy Carticel for 10 years.
Nicholas Chronos, president of St. Joseph's Translational Research Institute (Atlanta), said capillaries or even fully functional blood vessels are being grown. Collapsed vessels in advanced diabetics lead to $40,000 limb amputations as the only option. In these critical limb ischemia patients, infusing bone marrow helps blood vessels reconform, so circulation improves. Also, skeletal myoblasts have been taken from a French patient's leg and injected into her damaged heart, successfully repairing myocardial tissue.
Autologous cell therapy using keratinocytes for burn victims has also taken place. Ian Ratcliffe, CEO of Stemgent (San Diego), cited the example of a recent $600,000 windpipe reconstruction, adding, "To make it an efficient health care vehicle . . . we are a long way from that." Genzyme's Gregory said, "Cell therapies are one of the most complex . . . on the other hand, the potential is even greater."
Jan Nolta, director of the Stem Cell Program at the University of California (Berkeley), presented preclinical data on adult stem cells. These "paramedics of the body" have robust hematopoietic capacity and automatically migrate to hypoxia-damaged or inflamed tissues, while control cells lacking high levels of aldehyde dehydrogenase (ALDH), a conserved stem cell marker in mice and men, do not.
To confirm findings, glowing iron nanodust was added to the stems. Tracked by imaging, they went specifically to a hypoxic area of murine femoral artery ligation. Moreover, in a week there was blood flow and by 21 days, all appeared normal.
Andrew Balber, CSO of Aldagen (Durham, North Carolina), currently has four products in the clinic: Two are derived from cord blood, good for hematopoiesis; and two for bone marrow. In a mechanistic inquiry, the ALDH bright (br) cells were confirmed as the active component. Marrow is similar to cords, but half the ALDHbr cells differ, providing tissue repair capacity: ALD-301 will treat critical limb ischemia and ALD-201 is for heart repair.
Balber said, "In FDA jargon, these are minimally manipulated cells" since they are treated, but not cultured or manipulated, and re-implanted within 36 hours.
An investigation new drug application has been cleared and a clinical trial revealed ALDHbr could be obtained from all 21 patients, and treatment was safe and well-tolerated. A Phase II trial is planned.
"It's still a long way from routine delivery to patients," said Balber. "A lot of doctors don't want to be making cells." He added, "We can let them write a prescription and prepare cells for them [as a product]."
Since most stem cell research will take longer to translate into clinical reality, some low hanging fruit was mentioned: Cell banking, to save tissue for later; development of cheaper, more useful cell lines; stem differentiation in a meaningful, consistent manner for use in assays; and molecules that either help stems mobilize or target tissues.
Paul Grayson, president/CEO of Fate Therapeutics (La Jolla, California), added, "We look for sustainable shifts in cell fate" that continue after small molecule stem cell modulators (SMSCM) are removed. These SMSCM are near-term opportunities and follow a pharmaceutical development path.
Burrill concluded: "There is tremendous value at present, coming out of the tool-based side of stem cell research."