Series: Spotlight on Cell Therapy

Author: Nicole Forgione, 02/17/16
Rat spinal cord transplanted with green fluorescent protein (GFP) labeled neural progenitor cells. Credit: Mohamad Khazaei PhD, Scientific Associate, Fehlings Lab (Toronto)

Rat spinal cord transplanted with green fluorescent protein (GFP) labeled neural progenitor cells.
Credit: Mohamad Khazaei PhD, Scientific Associate, Fehlings Lab (Toronto)

Cell therapy is not a new idea. Bone marrow transplantation—the first ever cell therapy—has been around since the 1950s. Over half a century of research has brought important advancements, yet this technology has struggled to make it to prime time.

Understandably, there is scepticism about whether cell therapy will live up to the hype.

Recently, industry and government have been anything but sceptical, committing significant resources to translating and commercializing cell therapy for a wide range of conditions. Cell therapy is in the spotlight. In this series, I will explore how the research community, government, NGOs, and industry are responding to mounting expectations for this technology.

New Prospects in Cell Therapy for Spinal Cord Injury

In December 2015 my lab, under the supervision of Dr. Michael Fehlings, received an Ontario Institute for Regenerative Medicine (OIRM) grant that will support our research on stem cell therapies for spinal cord injury (SCI). We were particularly excited to win this grant because this is a different kind of funding.

Our mandate from OIRM is to work with a multidisciplinary team to move a cell-based therapy for SCI towards translation and commercialization. Increasingly, funding organizations are seeking a team approach to science—this is nothing new. Our challenge with this project is to ensure that our cell therapy is ready for Phase I clinical trial at the end of five years.

This innovative type of funding couldn’t have come at a better time for SCI research. Progress in clinical translation, and increased funding, signal that we are poised to make important advancements in the field. Below I’ll outline important clinical trials in cell therapy for SCI and explain the first-ever positive results from a trial being run by StemCells Inc.

Cell therapy for SCI is aimed at promoting neural regeneration that will lead to improved function. SCI results in a loss of movement and sensation below the level injury, and leaves patients with impairments that significantly impact their quality of life. More than half of the patients suffer neck (cervical) injuries that leave them with more profound deficits compared to patients who suffer mid-back (thoracic) injuries. Over the past 30 years, medical doctors have made incredible strides in the medical and surgical management of SCI, and have significantly lowered mortality rates. They have also developed very effective ways of intervening to minimize damage, stabilize patients, and later to rehabilitate them.

However, once a trauma has occurred, there are no treatments, cell-based or otherwise, that can meaningfully improve function beyond what occurs naturally. SCI patients need more treatment options. I, and others, believe cell therapy could be one of those options.

There are many ongoing clinical trials testing a variety of cell types, including neural stem cells, Schwann cells and mesenchymal stem cells, for their therapeutic potential in SCI. More recently, there has been a great deal of interest in using induced pluripotent stem cells (iPSCs) to develop autologous cell therapies for SCI. However, research in this area is still in the pre-clinical phase. Neural stem cells derived from foetal tissue or human embryonic stem cells (hESCs) have been showing the most promise in clinical trials. Below I summarize some of the key trials using these cells.

The California based company Geron pioneered clinical testing of cell therapy for SCI. Geron was the first to obtain approval to test hESCs in clinical trials. In a Phase I safety study, specialized hESCs (AST-OPC1 – oligodendrocyte progenitor cells) were transplanted into patients with thoracic SCI. After overcoming many obstacles to bring their therapy to clinical trial, Geron famously abandoned its Phase I study in 2011, citing financial reasons. In 2013, another U.S. company, Asterias Biotherapeutics, would acquire Geron’s hESC technology and pick up where it left off. After a successful Phase I safety study, Asterias moved to a Phase I/IIa dose escalation trial in patients with cervical SCI. The first patient in the Phase I/IIa trial received a transplant in June 2015.

In 2015, Neuralstem Inc. completed a Phase I study assessing the safety of spinal transplantation of neural stem cells derived from human foetal spinal cord (NSI-566). In this study, patients with thoracic SCI were treated with stem cells one to two years post-injury. A Phase I/II trial is slated to begin in South Korea, but is currently awaiting regulatory approval.

Some of the most promising results obtained with foetal-derived neural stem cells have come out of a recent trial run by U.S. based StemCells Inc. In 2015, StemCells Inc. reported exciting interim results from a Phase II study. Like the Asterias trial, this study was designed for patients with cervical SCI. Toronto Western Hospital, at the University Health Network, was one trial site in this international study. The Fehlings group participated in recruiting and treating patients, and had a key role in developing a specialized test to measure improvements in hand function called the GRASSP. Direct transplantation of neural stem cells into the spinal cord helped patients regain strength and movement below the level of injury, most importantly in their hands and arms.

In short, the StemCells Inc. trial is important because this is the first time we have seen patients get better.

The recent announcement of $20 million in federal funding, with a matched $20 million from industry, for a cell manufacturing facility in Toronto, is an indication of where cell therapy is headed in the near future. Once we achieve regulatory approval for cell therapies in SCI, the ultimate goal is to scale-up and commercialize this technology so that it is widely available. This is a challenging prospect and only achievable with collaboration between academia, government, and industry. Organizations like OIRM and its commercialization partner CCRM, are supporting the development of these crucial new relationships through funding and advocacy. It is an exciting time for cell therapy, and I for one am excited to have a front row seat.

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Nicole Forgione

Nicole Forgione

Nicole Forgione manages key relationships with industry and proposals for government funding at CCRM. A strong grounding in academic research helps her to understand the science behind new technologies in cell and gene therapy that CCRM is working to commercialize. Dr. Forgione obtained her Master’s degree from the University of Toronto (U of T) in the Department of Zoology and continued graduate studies at U of T in the Department of Cell and Systems Biology, where she completed a PhD in developmental neurobiology under the supervision of Dr. Vince Tropepe. Dr. Forgione went on to pursue studies in translational science with Dr. Michael Fehlings at the Krembil Research Institute in Toronto. Her post-doctoral work focused on animal models of spinal cord injury and cell based therapy for spinal cord regeneration. Nicole’s interest in science communication started early, with an undergraduate double major in English and Biology from Wilfrid Laurier University. Now she focuses her writing on anything and everything related to regenerative medicine technology. Follow Nicole on Twitter @DrNForgione.
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