Can a rare immune cell offer the key to slowing down senescence? A Bay Area startup looks to find out
For years, scientists have looked to curb aging and chronic diseases by clearing defunct cells with irreparable damage, also known as senescent cells. Drugmakers like Bristol Myers Squibb and Unity Biotechnology have toiled over senolytics to kill the stubborn cells. So when Robin Mansukhani was told it could be done using reawakened immune cells, he was intrigued.
Senescence serves a protective function. It occurs when cells are too damaged to keep dividing — for example, if they develop a cancerous mutation. But senescent cells also contribute to aging and other diseases, emitting toxic molecules that cause inflammation and tissue damage.
Back in 2018, Mansukhani was introduced to Anil Bhushan, a professor at the University of California, San Francisco, who was working on a way to weaponize invariant Natural Killer T (iNKT) cells against senescent cells to treat type 1 diabetes. iNKT cells act as a sort of surveillance system, eliminating foreign cells, but become less active with age and other factors.
“I followed senescence for a long time, but I never ever thought about it in the context of type 1 diabetes. So that data just kind of knocked me aside,” Mansukhani said.
He did his own research, then about six weeks later teamed up with Bhushan to launch Deciduous Therapeutics. While the team is no longer going after diabetes, they published a paper on Monday in Med linking in vivo iNKT cells with clearing senescent cells.
“These cells have long been of interest to people — they just, you know, haven’t really figured out what to do with them or what they really do,” Mansukhani, now CEO, said. “There was something in the senescent cell that said, OK, there’s a footprint here to an immune cell that’s going to talk to this senescent cell and clear it out. And that’s where things get exciting.”
iNKTs have two main attributes that make them an appealing target, Mansukhani explained. First, they have the same receptor, which doesn’t appear on any other cell in the body, allowing a high level of specificity. And they also operate in a natural negative feedback loop, that returns them to dormancy after a period of activity.
“Using iNKT-targeted therapy can piggyback on their exquisite, built-in specificity,” Bhushan said in a statement.
Using the approach, the scientists were able to improve blood glucose levels in mice with diet-induced obesity, and extend the lives of mice with lung fibrosis. Going forth, Mansukhani said the team is going to look at things like chronic kidney disease and cardiac fibrosis. He expects to hit the clinic in mid-to-late 2023.
“The rationale here was that, if this happens naturally in the body by the immune system, let’s just go back and understand that first, and then we can figure out what to do with that information once we actually understand that underlying first principle,” he said.