California’s state stem-cell agency has approved a total of nearly $20 million in grants toward trials to assess a potential treatment for spinal cord injuries, and a gene therapy designed to boost cell resistance to HIV, resulting in an AIDS-resistant blood system.

The California Institute for Regenerative Medicine (CIRM) awarded Asterias Biotherapeutics $14.3 million to test if transplantation of oligodendrocyte progenitor cells (OPCs) to the site of a spinal cord injury could help restore some function in patients. OPCs help stimulate the growth of nerve cells after an injury, and produce myelin, which conducts electrical signals in the spine.

OPCs were the subject of a Phase I safety trial by stem cell pioneer Geron launched in 2010, in which five patients with lower spinal cord injury were transplanted with no signs of serious side effects or safety concerns.

Geron halted that study a year later and sold its stem cell assets to Asterias’ parent company, BioTime, in 2012, saying it was ending all stem cell therapeutic programs. Instead, Geron has focused on developing the cancer drug imetelstat, which saw clinical holds placed by FDA earlier this year—a full hold on Phase 2 Geron-sponsored trials in essential thrombocythemia (eight patients) and multiple myeloma (two patients); and a partial clinical hold on an investigator-sponsored trial (IST) of the blood cancer treatment for myelofibrosis, involving clinical partner Mayo Clinic.

In the new trial, Asterias will give escalating doses of OPCs to patients with the most severe upper spinal cord injuries.

This new investment means we have a chance to build on the lessons we learned first time around,” says Jonathan Thomas, Ph.D., J.D., chair of CIRM’s governing Board, the Independent Citizens Oversight Committee (ICOC). “If this therapy can achieve even very modest improvements for patients, it could have an enormous impact on the quality of their life, and the lives of their families. “

In the other CIRM-approved trial, Sangamo BioSciences and John Zaia, M.D., of the Beckman Research Institute at the City of Hope won a $5.6 million grant from the agency to fund a Phase I clinical trial at City of Hope of a ZFP Therapeutic® for HIV/AIDS based on applying Sangamo's zinc finger nuclease (ZFN) genome-editing technology in hematopoietic stem/progenitor cells (HSPCs). 

Researchers plan to take blood stem cells from HIV infected individuals, then use a ZNF to cut out or mutate the CCR5 gene on those cells, making them resistant to HIV.

The CCR5 protein, found on immune system cells, is used by the AIDS virus to gain access and infect cells. CCR5 encodes a critical co-receptor for HIV infection of immune cells. A naturally occurring mutation of the CCR5 gene, CCR5 delta-32, results in the loss of expression of the CCR5 protein on the surface of immune cells. 

Individuals who carry the CCR5 delta-32 mutation on both copies of their CCR5 gene (CCR5 delta-32 homozygotes) are not susceptible to the most common strain of HIV.

The four-year grant provides matching funds to support evaluation of Sangamo's stem cell-based ZFP Therapeutic in HIV-infected individuals. The primary objective of the Phase I, open-label study is to evaluate the safety and tolerability of the infusion of autologous ZFN-genome-edited, CCR5-disrupted HSPCs (SB-728mR-HSPC) in HIV-1 infected subjects who are on ART, have no detectable virus in the circulation, but have sub-optimal CD4 T-cell levels. 

Secondary objectives of the trial are to assess the engraftment and biologic activity of the infused CCR5 modified HSPCs cells that may help to define primary efficacy endpoints for future studies. These secondary objectives include engraftment, persistence and trafficking of the CCR5-disrupted HSPCs, effect of these cells on  plasma viral loads during treatment interruption from ART and longitudinal changes in the viral reservoir. 

Funding for both trials was approved under CIRM’s Strategic Partnership Award program, designed to attract more industry investment in research projects funded by the stem cell agency, and accelerate the most promising projects into clinical trials. Asterias and Sangamo will match the funds they will receive from CIRM, the agency said.

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