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Freelance health journalist and former neuroscientist interested in a wide variety of life science topics. David also writes for The Guardian, BBC, National Geographic, NBC News, Wired, TIME and others.
Ever since the beginning of the Covid-19 pandemic, there have repeated indications of an abnormal spike in cases of type 1 diabetes, a progressive autoimmune disease where the immune system attacks the body’s own insulin-producing beta cells in the pancreas.
In summer 2020, hospitals in North West London reported that they were seeing double the number of type 1 diabetes cases following the first wave of Covid-19 in the UK. Since then similar statistics have been reported around the world, with a Nature paper last year reporting that Covid-19 survivors were 39% more likely to have a new diabetes diagnosis compared to those who had not been infected.
For those familiar with the disease, this came as little surprise. Type 1 diabetes has long been linked with various viral triggers, from cytomegalovirus to mumps and rubella. But while this spike in cases has been a source of concern for many healthcare providers, a range of new breakthroughs have fuelled optimism that we may be closing in on ways of perhaps halting the disease in its tracks, and even finding a way to cure it altogether.
“We are actually getting to a point where the past 30 years of research will have therapies available clinically.” explains Carla Greenbaum, who directs the Diabetes Research Program at the Benaroya Research Institute in Seattle, and has 5,381 topic citations for type 1 diabetes on Insciter.com.
“There is robust data collected over decades in multiple countries so that we can identify people who are going to develop type 1 diabetes, and there are now at least seven therapies that have shown to be effective in altering disease course soon after diagnosis.”
One of the biggest hopes is different forms of immunotherapy which could be particularly useful for those newly diagnosed with type 1 diabetes. At this point, it is estimated that up to 20% of beta cells in the pancreas are still alive, and so any therapy which blocked or slowed down the immune system attack might be able to preserve some normal pancreatic function.
Various approaches are currently being trialled. At Cardiff University, a team of researchers are investigating a way of reprogramming B cells, a type of white blood cell which begins to mistakenly attack the pancreas. They have found that a particular protein on B cells called CXCR3 may be involved in this dysfunctional process, and if so, targeting CXCR3 may provide one way of stopping the immune attack.
Other scientists are looking at forms of immune suppressants which dampen down the activity of B and T cells so they cause less damage to the pancreas. Researchers at Queen Mary University in London have also identified a drug which appears to enhance another form of immune cell called regulatory T cells which can protect the pancreas from attack, potentially helping to halt the progression of type 1 diabetes.
Jeffrey Bluestone, who directs the Hormone Research Institute in the Diabetes Center at the University of California, San Francisco, and has 10,505 citations topic citations for type 1 diabetes on Insciter.com, says that the development of immunotherapies for type 1 diabetes have been aided by breakthroughs in cancer immunotherapy in recent years.
“I think many of the pathways identified and targeted in cancer immunotherapies, ranging from checkpoint inhibitors to cell therapies to manipulating the tumour microenvironment, can be adapted to the treatment of autoimmune diseases.” says Bluestone who is also CEO of Sonoma Biotherapeutics which develop therapies for autoimmune diseases.
The Holy Grail for many diabetes scientists is to identify people who are potentially at risk of type 1 diabetes, and prescribe them an immunotherapy which can prevent the disease happening altogether.
The presence of certain autoantibodies – proteins which bind to beta cells, signalling that the cell needs to be destroyed – are a tell-tale sign that an individual is at risk of developing the disease, and could potentially be used in future screening programs for type 1 diabetes.
Since 2019, this concept has become more realistic after scientists from the global TrialNet research consortium identified an immunotherapy called Teplizumab, developed by US-based biotech ProventionBio, which appears to prevent T cells from being activated, preventing them attacking beta cells. Since then, a clinical trial has shown that Teplizumab can delay the onset of type 1 diabetes in at-risk individuals by three years.
So far the FDA has been reluctant to approve Teplizumab, citing the potential safety concerns of prescribing an immunosuppressant drug to people who have yet to be diagnosed with the disease. However Bluestone, who was involved in the development of Teplizumab and sits on the board of ProventionBio, remains hopeful that regulators can eventually be convinced.
“I remain optimistic that Teplizumab will at some point cross the finish line, and be a game changer for the treatment of type 1 diabetes,” he says. “The issues are that this is not a deadly disease for an overwhelming number of patients, and it is a disease of children in most cases so the bar for safety is very high, and endocrinologists and parents have been resistant to chronic treatments with side effects.”
For people who have been living with type 1 diabetes for many years, one of the main hopes of an eventual cure is stem cell derived beta cell transplants.
US based company Vertex Pharmaceuticals are currently pursuing Phase I/II clinical trials of such a therapy, administered via an injection. Last October they announced that the first patient had been dosed with the new treatment.
The initial results have been promising, with the patient – who had previously suffered five potentially life-threatening hypoglycaemic episodes – producing and maintaining a steady flow of insulin after 90 days, although the challenge will be maintaining this in the longer term. Previous beta cell transplantation attempts have faced setbacks as the immune system eventually rejects the new cells while prescribing immunosuppressants alongside the treatment leads to undesirable side effects.
However, a team of researchers at Northwestern University, Illinois published a paper earlier this month which may provide a solution to the problem. Through encasing rapamycin – a commonly used immunosuppressant – in a nanoparticle, they were able to suppress T cells and prevent them attacking beta cell transplants in mice, without toxic side effects. The scientists are now attempting to find industrial partners to move this into a clinical trial.
“I have been impressed by the progress both in moving the field of stem cell-derived beta cells, and I am convinced that this is the future for treating established type 1 diabetes,” says Bluestone. “I think that with a combination of new gene editing technologies, the use of encapsulation, and companion immune therapies, we are likely to get to a place where allogeneic and perhaps even xenogeneic grafts are feasible.”
Greenbaum is confident that in the coming years, scientists will develop ever more promising solutions to the disease.
“I’ve been working on this problem for more than 30 years, and I finally do see the light at the end of the tunnel,” she says.
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