Experimental treatment shows early promise for protecting insulin-producing cells in type 1 diabetes

What is ZnT8?

ZnT8 (short for zinc-transporter 8) is a protein found almost exclusively in the membranes of the insulin producing cells (beta cells) in the pancreas. 

ZnT8 is also one of the main targets of the immune system when someone develops type 1 diabetes (T1D). Many people who develop T1D produce antibodies against ZnT8, and testing for these antibodies is often used to help diagnose early-stage T1D.  

The paper also suggests that ZnT8 may play another role in type 1 diabetes by contributing to inflammation. It appears to put extra strain on the parts of insulin-producing cells that prepare and store insulin. Over time, this added stress can trigger inflammation, making it harder for these cells to work properly and increasing the risk that they will die.

What did the researchers do, and what were the results?

The research team used specially designed antibodies that bind to ZnT8 on the surface of beta cells, known as Isle43. Rather than triggering immune destruction, these antibodies were engineered to be taken up by the cells and acted as chaperones for ZnT8. This led to less stress and inflammation. 

The results showed that the Isle43 antibody slowed disease progression and reversed T1D for newly diagnosed stage 3 T1D in animal models, with sustained results after the treatment was stopped. Isle43 also reduced signs of cellular stress in beta cells and decreased the expression of molecules that make beta cells visible to the immune attack. The treated animal models retained more beta cells than untreated animals.  

Keeping more beta cells is a positive thing, as there is no better insulin than your own.  

These findings suggest that targeting ZnT8 could become a new way to protect and preserve surviving beta cells during the initial stages of T1D. Rather than directly suppressing the immune system, the treatment appears to make beta cells more resilient to inflammatory stress.

What does this mean for people with T1D?

If this approach is successful in humans, it could help to preserve the remaining insulin production after diagnosis and slow down the progression of T1D. The treatment could be used alongside immune therapies, such as teplizumab, to extend the time frame before stage 3 T1D diagnosis. It could also be used to assist in islet transplants, helping to protect the transplanted islets so they can survive for longer. 

However, it is important to emphasise that this research is still at a very early stage. The positive results were seen in mice and human cells within a lab setting, not in people with T1D. It is therefore too early to know whether the treatment will be safe or effective. 

What are the next stages of this research?

The research team will next test their methods in models with human immune system components, before moving to test them in human participants. There also needs to be a deeper level of understanding around how the Isle43 antibody works and interacts with ZnT8 within the body and how it triggers the specific protective pathways. This is important to determine how safe the treatment would be in humans, and to make sure there aren’t any long-term side effects. 

If there are further positive results, this treatment will progress to early-phase clinical trials in people with T1D to evaluate safety, the best dose and its effectiveness.