Has the potential to be used for other allergies and autoimmune disorders, including type 1 diabetes
A group of University of California, Los Angeles immunologists has developed a novel nanoparticle that could offer a new way to treat peanut allergies. Currently, the only approved treatment for peanut allergies reduces the severity of the allergic reaction, but it takes months to take effect.
Peanut allergies affect one in 50 children, and the most severe cases lead to a potentially deadly immune reaction called anaphylactic shock.
The new nanoparticle, measured in billionths of a meter, delivers mRNA to specific cells in the liver, teaching the body’s natural defences to tolerate peanut proteins. The researchers found that the nanoparticle not only reversed peanut allergies but also prevented them from developing in mice.
The researchers focused on the liver because it is trained not to respond to every challenge and because it is home to antigen-presenting cells, which collect foreign proteins and train the immune system to tolerate them. The scientists improved on the design of their previous nanoparticle by adding a sugar molecule on its surface that specifically binds to antigen-presenting cells. Using mRNA was another step forward.
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To evaluate whether their upgraded nanoparticle would prevent peanut allergies, the researchers gave it to six mice in two doses, a week apart. Another group of six mice got a nanoparticle with the same mRNA payload but no targeting sugar on its surface; six other mice got the upgraded nanoparticle but with mRNA inside that didn’t code for any protein or epitope; and a third group of six got no nanoparticle at all.
Starting one week after the second dose, they fed the mice a crude peanut protein extract to sensitize them to the peanut allergens. Another week later, they exposed the mice to peanut protein to trigger anaphylactic shock.
Mice pretreated with the upgraded nanoparticle showed milder symptoms compared to those who received a nanoparticle with no targeting sugar. In contrast, more-serious symptoms appeared in the control group receiving no treatment and the group getting a targeted nanoparticle with noncoding mRNA.
The scientists repeated the experiment, changing the order of operations so that mice were sensitized to peanut protein before receiving the nanoparticle. Again, the upgraded nanoparticle outperformed a similar one that lacked the targeting sugar, and both produced far milder symptoms than the researchers observed in mice given no treatment or a nanoparticle containing noncoding mRNA.
In both versions of the experiment, the scientists measured the levels of specific immune cells as well as certain antibodies, enzymes, and cytokines, which confirmed that the upgraded nanoparticle had increased the animals’ tolerance for peanut protein.
The researchers believe that the nanoparticle has the potential to be used for other allergies and autoimmune disorders. They are exploring whether the nanoparticle could be used to treat type 1 diabetes, a disease in which the immune system attacks cells in the pancreas that enable the body to get energy from food.
Dana Wilson is a freelance writer based in Edmonton.
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