JDRF-funded scientists at the University of Bremen in Germany have found that the therapy neratinib, used in cancer treatment, may stop the immune system’s destruction of beta cells in type 1 diabetes and preserve insulin production.
The research, published in the journal Nature Communications, shows that neratinib protected beta cells and allowed them to keep producing insulin, when tested in mice.
At diagnosis, people with type 1 have between 10 and 20% of their beta cells remaining. This is an important first step towards a therapy that could enable people with type 1 to retain their remaining insulin-producing beta cells, leading to much better management of their blood glucose levels and less reliance on insulin injections or pumps.
Why did they do this research?
A loss of insulin-producing beta cells is a hallmark of type 1 diabetes and at diagnosis, people with type 1 generally have between 10 and 20% of their beta cells remaining. This results in a loss of insulin production, and people with type 1 have to rely on insulin injections or an insulin pump in order to manage their blood glucose levels.
Even so, blood glucose management can be tricky, and people with type 1 remain outside of the recommended blood glucose target range for an average of ten hours per day. This increases the risk of complications such as severe hypoglycaemia or retinopathy.
Neratinib is a therapy licensed for use in cancer treatment both in the US and the UK. It works by stopping cancer cells from growing. Recently, scientists have suggested that the therapy could also block the cellular mechanisms that cause beta cells to die in type 1. The group at the University of Bremen, supported by JDRF, decided to test this to see if neratinib could be a potential therapy for people with type 1.
What did they do?
First, the group tested neratinib’s ability to prevent the death of lab-grown beta-like cells when put in conditions that mimicked those in type 1.
Following this, they then tested how well neratinib protected human beta cells from death by treating donated human beta cells with the drug while in diabetes-like conditions.
Finally, they tested the drug in mice that had a condition similar to type 1 to see how it would affect their ability to control their blood glucose.
What did they find?
In both the lab-grown beta-like cells and the human beta cells, neratinib prevented cell death when they were in conditions mimicking type 1. By contrast, without treatment with neratinib, the both the beta-like cells and the human beta cells died in the same conditions.
When the group gave neratinib to the mice with a diabetes-like condition, the mice were able to make more insulin than the untreated mice in response to glucose. In turn, neratinib-treated mice had better glucose tolerance and significantly lower blood glucose levels than untreated mice throughout the 35 days of the study.
What does this mean for type 1?
Although still in its early stages, this research reveals an exciting possible use for the cancer therapy neratinib in preventing beta cell death and preserving insulin production in type 1. In the future, this therapy could allow people with type 1 to continue to produce some of their own insulin, making them less reliant on insulin injections or pumps while having better blood glucose management. Coupled with a way to regenerate the beta cells already lost, therapies – such as neratinib – which prevent beta cell death may even lead to a functional cure for type 1.