Existing drug curtails immune attack in type 1 diabetes
Posted on 02 July 2019
JDRF-funded clinical trials have shown that an existing drug is able to slow type 1 diabetes progression in the newly diagnosed. Anti-Thymocyte Globulin (ATG) moderates the immune response and is mainly used to prevent transplant rejection. Results from the trial, published this month, showed that a low dose of ATG significantly reduced the decline of insulin production and brought down HbA1c levels in people newly diagnosed with type 1.
The researchers think that ATG may be able to slow the progress of type 1 or even prevent its development altogether. There is also hope for people already living with type 1 as, combined with methods to regrow beta cells, dampening down the immune attack is a crucial part of a functional cure.
Why did they do this research?
Type 1 develops when the immune system mistakenly attacks insulin-producing beta cells in the pancreas. This attack is driven by a type of immune cell – called a T cell – which has gone rogue. The group of researchers have previously shown that ATG targets and destroys this type of cell – although the high doses they used didn’t preserve insulin production.
The researchers therefore decided to test the drug at a different dose to see if a ‘sweet spot’ could be achieved where rogue T cells could be killed and insulin production could be preserved. This would maximise the potential benefits of ATG therapy to people with type 1.
They also tried it in combination with a cell-growth supplement called GCSF, as this has been shown to increase the number of anti-inflammatory immune cells that can stop the actions of type 1-causing rogue T cells.
What did they do?
A collaborative clinical trial of the drug was carried out across 14 JDRF-funded TrialNet sites in the US. The researchers recruited 81 people between 12 and 45 years of age from across the US who had very recently been diagnosed with type 1.
Over the course of six weeks, they were given infusions of either ATG alone, ATG with GCSF or a placebo, before being monitored for the next two years. During this time they also continued taking insulin as normal.
What did they find?
A low dose of ATG significantly slowed the decline of insulin production over two years. This didn’t happen when it was combined with GCSF, meaning that boosting the anti-inflammatory immune cells didn’t appear to have any effect on preserving insulin production.
After the two-year endpoint, HbA1c levels were found to be much lower in the groups given infusions of ATG and ATG with GCSF infusions than those given a placebo, meaning that average blood glucose levels were lower for these groups.
The researchers looked at the immune cells and noted that in the people given ATG or ATG with GCSF, the numbers of anti-inflammatory immune cells versus the numbers of rogue T cells had gone up and these cells now also showed signs of being more adept at stopping the rogue T cells.
Importantly, those given either drug combination did not experience any severe side effects and no instances of severe hypoglycaemia. In fact, there were nearly twice as many side effects reported in the placebo group.
What does this mean for type 1?
In the future, people with newly-diagnosed type 1 could use ATG to slow down the progression of the condition and reduce spikes in their blood glucose levels. The researchers also hope that the drug could be used to prevent the onset of type 1 in those at high risk. Furthermore, combined with a way to regrow beta cells, research into therapies which stop the immune attack could one day lead to a cure for type 1.
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