Stem Cell Trials Moving Along

Posted by Sam Maddox in Research News on August 31, 2015 # Research

Asterias Biotherapeutics announced today that a third patient with a cervical spinal cord injury has been dosed with embryonic stem cells (code-named AST-OPC1) as part of the company’s acute (14 to 30 days post injury) Phase 1/2a clinical trial of oligodendrocyte progenitor (OP) cells. In case you don’t have your scorecard in front of you, this is the continuation of the work the biotech company Geron got started and then, five years ago, suddenly quit after just five patients.

OP cells are stem cells that have been allowed to take on an identify toward becoming oligodendrocytes, important support cells for nervous system function. Two former Geron guys bought the rights to the OP cell lines and under the Asterias banner, modified the original trial to focus on quads, and at much higher doses.

How are these cells said to work? Asterias think there may be three possibilities.

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 survival, regrowth and conduction of nerve impulses through axons at the injury site. In preclinical animal testing, AST-OPC1 administration led to remyelination of axons, improved hindlimb and forelimb locomotor function, dramatic reductions in injury-related cavitation and significant preservation of myelinated axons traversing the injury site.

Long time readers here will recall that the animal data that Geron based its first study on came from the UC Irvine lab of Hans Keirstead. Hans is no doubt enjoying OPC redux; his research career, however, has veered toward cancer immunotherapy (see Caladrius).

The first person to get Asterias going was treated at the Shepherd Center last June, less than a month after he broke his neck falling from a tree. According the company, this man -- who we now know from various social media, is Jared Grier, a 19-year-old mechanical engineering student from Connecticut -- went from ASIA A, meaning no motor or sensory function below C6, to ASIA B, meaning the injury is now consider incomplete.

Asterias did not hesitate to make some PR hay: From a company press release: “The principal investigator at Shepherd Center, Dr. Donald Peck Leslie, said, ‘This progress in the first patient is very encouraging and is observed in less than 5 percent of our AIS A patients at this stage of their recovery.’”

Two others have been enrolled in the first phase of the new study, both getting injections at Rush in Chicago of two million cells. This is a safety test but biotech companies, and the investment press, love to hear about even the slightest hint of recovery. A second study cohort will be treated soon -- five patients will receive 10 million stem cells, five will get 20 million. Said Dr. Edward Wirth, Chief Medical Officer of Asterias. “The safety data in this first cohort now paves the way for testing the higher doses of AST-OPC1 (10-20 million cells) that we believe correspond most closely to the doses that showed the greatest efficacy in animal studies.”

And then? Asterias wants to scale up to 40 patients.

Upon achievement of initial safety data from the first two cohorts of this study, Asterias plans to seek concurrence from the U.S. Food and Drug Administration to increase the robustness of the proof of concept in the Phase 1/2a clinical trial by expanding enrollment from 13 patients to up to 40 patients. The Company believes this change will increase the statistical confidence of the safety and efficacy readouts, reduce the risks of the AST-OPC1 program and position the product for potential accelerated regulatory approvals. Asterias has received a Strategic Partnerships Award grant from the California Institute for Regenerative Medicine, which provides $14.3 million of non-dilutive funding for the Phase 1/2a clinical trial and other product development activities for AST-OPC1.

Other stem cell news:

StemCells, Inc, whose stock is listed as STEM, is midstream in its Pathway trial, which, says the company, “will evaluate the safety and efficacy of transplanting ... proprietary human neural stem cells (HuCNS-SC cells), into patients with traumatic injury in the cervical region of the spinal cord. The trial will enroll approximately 52 subjects and follow the patients for 12 months post-transplant.”

StemCells, Inc. uses a stem cell line derived from a fetal spinal cord. If Asterias can be said to be using Keirstead’s cell line, StemCells cells are the laboratory offspring of Brian and Aileen Anderson, a husband wife science duo also from UC Irvine; Aileen is a member of Reeve International Research Consortium on Spinal Cord Injury.

It’s the first blinded, controlled clinical trial to be conducted using human neural stem cells, says Dr. Stephen Huhn, M.D., Chief Medical Officer at StemCells, Inc. Pathway builds on modest but apparent success in a Phase I trial of the neural stem cells; seven of 12 patients showed measurable sensory recovery.

Neuralstem, listed on the exchange as CUR, dosed a fourth SCI patient (out of four, all at UC San Diego) in July. This is an early safety trial of is neural stem cell line, NSI-566, in cervically injured patients, one to two years post injury. No reports spotted on whether the cells are doing anything; the company thinks they may rewire the damaged cord.

Stop the presses, STEM and CUR don’t get along. Both companies use similar fetal-derived cell lines. Too close for comfort? Eight years ago STEM sued CUR for patent infringement. The lawyers duked it out and the winner, according to The U.S. District Court of Maryland was Neuralstem. From a CUR press release:

In its 29-page Memorandum Opinion, the U.S. District Court for the District of Maryland ruled that a third-party scientist is a co-owner and co-inventor of the patents-in-suit. As a result, StemCells, Inc. lacked standing on its own to bring its patent infringement claims against Neuralstem, Inc. and the case was dismissed with prejudice.

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