CIRM OKs $20M toward Studies of Spinal Cord Injury, HIV Therapies
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.