The first human trial of insulin-producing cells that have been gene-edited to evade immune attack is a success so far. The cells have survived and produced insulin for a month after being injected into a 42-year-old man with type 1 diabetes early in December.
As a precaution, only a small number of insulin-producing beta cells were injected into a forearm muscle in this initial test, so the man still needs insulin injections. It also remains to be seen how long the cells will survive.
Nonetheless, the results are promising, at Uppsala University Hospital in Sweden, where the trial was done, . 鈥淸The results] provide real hope that a scalable, curative treatment for patients with type 1 diabetes鈥� is possible,鈥� he said.
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Beta cells in the pancreas normally regulate blood sugar levels by releasing the hormone insulin when blood sugar levels rise. But in, some people, the immune system attacks and kills beta cells for reasons that aren鈥檛 understood. The condition, called type 1 diabetes, is deadly unless treated by injecting insulin.
The technology for doing this has improved greatly. There are now wearable devices that continuously monitor blood glucose levels and can be wirelessly linked to small pumps that automatically inject insulin.
However, the parts of the sensor and injector that enter the body have to be replaced every few days, and even the best devices don鈥檛 control blood sugar as well as actual beta cells. So, for decades, researchers have been exploring ways of replacing the lost cells.
The transplantation of beta cells taken from dead donors became an in 2023, but recipients have to take drugs to suppress the autoimmune response that killed their own beta cells, as well as to prevent the donor cells being attacked as foreign. Because immunosuppressive drugs can have serious side effects, this approach is unlikely to be widely used.
One way to avoid immune suppression is to transplant beta cells encapsulated in containers with holes so small that they keep out immune proteins and cells. This has worked for up to several months in human trials, but and the beta cells die.
Seattle-based Sana Biotechnology is instead gene-editing cells so they can evade the immune system. Two edits block the production of HLA1 and HLA2 proteins, which protrude from the outside of cells and allow the immune system to recognise the cells as self or foreign.
Because the immune system also kills any cells that lack HLA proteins, a third edit boosts levels of the protein聽CD47, which acts as a 鈥渄on鈥檛 kill me鈥� sign on the outside of cells.
The initial results confirm that beta cells with these edits were protected from the man鈥檚 autoimmune response against beta cells and from rejection as foreign cells, says at the University of Pennsylvania. In principle, injecting a higher number of cells should eliminate the need for insulin injections.
鈥淭his is a major step towards the eventual goal of beta-cell replacement therapy for type 1 diabetes without the need for immunosuppression,鈥� says Rickels.
The potential downside of this approach is that if any of the modified cells turn cancerous, the tumours would go undetected by the immune system. The cells were injected into the forearm because it鈥檚 easier to spot any potential problems here than in sites deeper in the body.
However, in tests in animals, Sana has shown that the modified cells could be killed off by injecting an antibody that targets CD47. 鈥淭his provides an additional safety measure should a problem develop,鈥� says Rickels.
