The company indicated that it had new results from its transthyretin amyloidosis (ATTR) non-human primate (NHP) studies, that it conducted in collaboration with Regeneron Pharmaceuticals. It was related to “its enhancements of the cargo components of its lipid nanoparticle (LNP)-based delivery system.” They want to add that data into the IND.
“We are elated to have achieved such impressive and compelling editing and protein knockdown results in our NHP studies,” stated John Leonard, the company’s president and chief executive officer. “We believe that this approach, while introducing a relatively short delay to our previous IND timeline, will ultimately yield the best possible treatment option for patients—one that we hope will clearly advance the standard of care well beyond approved and potential therapies for the treatment of ATTR.”
That didn’t prevent some observers from wondering if there were other reasons for the delay, particularly since it came the day after a new study was published suggesting that CRISPR/Cas9 causes an immune reaction that prevents treatments from working. This new article was published in the journal Nature Medicine. The study stated, “Preexisting immunity against therapeutic gene vectors or their cargo can decrease the efficacy of a potentially curative treatment and may pose significant safety issues.”
It’s not the first time the problem has been raised. An article on bioRxiv in January advanced the topic as well. It stated, “This data demonstrates that there are pre-existing humoral and cell-mediated adaptive immune responses to Cas9 in humans, a factor which must be taken into account as the CRISPR-Cas9 system moves forward into clinical trials.”
In the new study, researchers observed that 96 percent of patients in the study had T-cell based immunity against Cas9, with 85 percent of the patients having antibodies against it. The earlier study indicated that 65 percent had antibodies against Cas9, but didn’t detect T-cell activity against it.
Michael Schmueck-Henneresse of Charite University Medicine Berlin, who led the most recent study, told Xconomy, “But it made sense because the Streptococcus pyogenes bacterium is one of the most common causes for bacterial infections in humans and we have all been through multiple infections and potentially even been colonized by it.”
An Intellia spokesperson told the Boston Business Journal that the study had nothing to do with the delay, a sentiment echoed by Leonard at the third-quarter conference call.
“Given the short treatment course that we anticipate, that shouldn’t be a problem for a patient,” Leonard said. “We can immuno-suppress, if necessary, but right now, it is not a major issue for us. I don’t measure progress by the first IND date, but by the medicine we are able to deliver.”
CRISPR allows researchers to quickly and precisely identify gene sequences that they can then cut out and replace. But it’s not without its problems and concerns. There have been worries that the technique causes off-target cuts that could cause cancer and other disorders, and the possibility that the body’s DNA repair mechanisms kick in and reverse the changes. The new studies suggest that, because the enzymes used to cut the DNA come from common bacteria, humans have immunity against them.
A recent article by Andre Choulika, founder, chairman and chief executive officer of Cellectis, however, expressed concern that the U.S. was losing the gene-editing “race,” comparing it to the “space race” in the 1950s and 1960s between the U.S. and the U.S.S.R.
He wrote, “The emergence of CRISPR in 2012 energized the gene-editing field. Since then, the number of new gene editors has been growing exponentially. That explosive growth has triggered a shift in the balance of research and development power, with Eastern Asian countries beginning to dominate the research. Researchers in these countries have been engineering living species one after another in series of different applications, filing patents, and conquering unexplored spaces.”
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