We’ve taken a look at the latest exciting research news in type 1 diabetes and what it could mean for people with the condition: a first-of-its-kind gene therapy entering clinical trials that could transform daily life with type 1, and the potential of a new anti-rejection drug to improve the success of islet cell transplants.
New gene therapy for type 1 to be tested in a world-first clinical trial
This year, researchers plan to test the safety and effectiveness of a gene therapy called KRIYA-839 in a clinical trial involving people living with type 1 diabetes.
In early studies in animals with type 1, KRIYA-839 was found to be safe and effective at bringing down blood sugars. In some cases, its blood sugar-lowering effects lasted up to four years after a single treatment.
These positive results have opened the door to testing KRIYA-839 in people with type 1 diabetes. The treatment involves injections of KRIYA-839 into the thigh muscle. This will deliver two genes - one which gives cells instructions for producing insulin, and another for producing a protein called glucokinase.
Unlike gene editing, this approach doesn’t directly change a person’s DNA. Instead, it uses a harmless virus, called an adeno-associated virus (AAV), to deliver the genetic instructions into cells. This type of gene therapy is already approved to treat some rare genetic conditions.
In KRIYA-839, the added genes are designed to give muscle cells a new job: producing insulin and releasing it when blood sugar levels rise.
Glucokinase acts like a built-in blood sugar sensor. It stays mostly inactive when blood sugar is low. When blood sugar is high, it switches on and helps move sugar out of the bloodstream and into cells more effectively.
In the upcoming PROGRESS trial, researchers plan to recruit adults with type 1 diabetes whose HbA1c is above 53 mmol/mol (7%) and who are using closed loop technology to try the new gene therapy. Full details about when recruitment will begin, how many people will take part, and where the trial sites will be located haven’t yet been confirmed.
As part of the treatment, participants will also take a short course of drugs to temporarily dampen down the immune system. This helps prevent the body from reacting too strongly to the virus and allows the muscle cells to more effectively take up the genetic material.
This early trial is designed to explore the safety of the gene therapy. It will give researchers a first look at whether the treatment works in people with type 1 diabetes.
If the trial and further larger trials are successful, this innovative treatment could give us a new way to help people with type 1 diabetes keep their blood sugar levels in range for longer, reduce insulin doses, and ease some of the daily grind of managing the condition.
The exciting potential of anti-rejection drug for islet cell transplants
Early results from a clinical trial suggest that a new drug - tegoprubart - can protect transplanted insulin-producing cells in people with type 1 diabetes, without harmful side effects.
Islet cell transplants involve transplanting insulin-producing cells from a donor pancreas into someone with type 1 diabetes. This can restore the body’s ability to make its own insulin, for a time. But because the cells come from a donor, the immune system sees them as foreign and tries to destroy them.
To prevent this, people must take powerful immunosuppressing drugs. These drugs can have serious side effects, including kidney damage and an increased risk of infection. Because of this, islet transplants are currently only offered to adults with type 1 who have frequent severe hypos and impaired hypo awareness, or who’ve had a kidney transplant alongside severe hypos.
Unlike existing drugs that suppress the whole immune system, tegoprupart only targets a specific part that’s involved in transplant rejection. This precise action could mean that tegoprupart can prevent rejection of transplanted insulin-producing cells without as many side effects.
Researchers at the University of Chicago Medicine enrolled 12 adults with type 1 diabetes on their trial to test tegoprubart alongside islet transplants. Participants had lived with type 1 for around 33 years and started the trial with an average HbA1c of 64 mmol/mol (8.0%).
Among the first ten participants who were at least four weeks past their transplant, all were producing their own insulin and able to stop insulin therapy. On average, their most recent HbA1c result was 35 mmol/mol (5.35%). Notably, the first three people treated haven’t needed to take insulin for over a year.
Tegoprubart was generally well tolerated by the participants, and side effects were treatable. There was no evidence of raised blood pressure, kidney damage, or nerve problems – which are common effects of other anti-rejection drugs.
These early findings indicate tegoprubart’s potential to make life-changing islet transplants safer, more effective, and available to a wider group of people with type 1 diabetes.
Next, the researchers plan to conduct bigger, longer clinical trials to confirm tegoprubart’s safety and effectiveness, and to better understand how long it could help transplanted donor cells survive and produce insulin.
Looking further ahead, tegoprubart may be explored as a way to protect lab-made beta cells, supporting emerging beta cell replacement therapies. You can explore the Type 1 diabetes Grand Challenge website to find out more about this exciting area of research.
