The Science & Technology desk gathers a weekly digest with impactful and interesting research publications and developments at Stanford. Read the latest in this week’s Research Roundup.
CAR T-Cell Therapy “brain fog”
CAR T-cells are a type of modified T cells from the immune system, designed to recognize and eliminate cancerous cells, a more selective approach compared to the general killing of infectious cells that T-cells perform. While this therapy has held lots of promise in the scientific community, it can come with an issue that researchers are hoping to treat.
In a Stanford-led study published in Cell, researchers showed that CAR T-cell therapy leads to mild cognitive impairments, resulting in a “brain fog.”
How exactly does this happen? Researchers found that, upon CAR T-cell therapy, microglia – the brain’s immune cells – produces chemicals like cytokines and chemokines as part of its inflammatory response. These disrupt the myelin sheath around axons, which are critical for effective nerve signal transmission, which over time can produce some brain fog.
To examine potential treatments to this issue, researchers tried two strategies that were both successful. The first was depleting the microglia in the brains of the mice that were in the experiment, allowing regrowth of proper, functional microglia. The second was giving the mice a medication that blocks a receptor to which chemokines attach.
Senior author of the study Michelle Monje MD ‘04 Ph.D. ‘04 stressed that CAR T-cell therapy is still entirely promising, especially with the feasibility of potential treatments to combat this “brain fog.”
“CAR-T cell therapy is enormously promising … we need to understand all its possible long-term effects, including this newly recognized syndrome of immunotherapy-related cognitive impairment, so we can develop therapeutic approaches to fix it,” Monje told Stanford Medicine.
Meet CRISPR, the mailman
We normally think of CRISPR as the “molecular scissors” that can slice and edit genetic code. However, it turns out that it can be used in another creative way to solve an RNA-based issue.
In neurological conditions like amyotrophic lateral sclerosis (ALS) or major effects to the spinal cord, RNA segments are prevented from being moved to the injured locations. Since RNA is vital in translating proteins to repair neuronal injuries, inhibiting RNA’s proper function can lead to permanent damage.
To mitigate this issue, Stanford researchers developed a CRISPR Cas-13 variant (CRISPR-TO) that can help transport RNA segments to injured neuronal locations.
Using specific molecular signals, the researchers directed numerous RNA segments toward their specific “addresses” within the cell to observe which had a positive impact on neuronal growth. The researchers identified multiple beneficial candidates.
CRISPR-TO may potentially also aid in making RNA-based medicines more precise.
Stanley Qi, an associate professor of bioengineering who was the senior author of the study, expressed the importance of this technology.
“Imagine being able to specifically target damaged sites within a neuron, repairing them, and promoting their regrowth – this is what our technology achieves,” Qi told Stanford Report.