Our team recently attended JDRF’s 30th anniversary celebrations in Guildhall in the City of London. The event brought together some high profile guests, supporters, scientists and patient advocates to discuss the current state of the type 1 diabetes research field.

JDRF UK’s President, The Duchess of Cornwall, the Prime Minister, Theresa May – who was diagnosed with type 1 diabetes in 2013 – volunteers and donators all re-pledged their commitment to the charity’s mission to find a cure.

Attendees also reminisced on how JDRF helped type 1 diabetes research progress all these years and how this work paved the way for the historic artificial pancreas success.

 

 

AP FDA approval: A momentous achievement

Being able to give type 1 diabetes patients access to the hybrid closed loop system technology was the result of over a decade of work and a strong push for the FDA to prioritise this project a number of years ago.

It is estimated that JDRF’s work and funding accelerated the process of getting the Medtronic’s 670G artificial pancreas system FDA approved by five to seven years.

This life-changing breakthrough comes after years of laying the ground work to accelerate ways to prevent and treat this disease through dedicated partnership, collaboratio, funding and advocacy.

Back in 2013, the Type 1 Diabetes Research Roadmap project – which set out to identify key strengths of type 1 diabetes research in the UK and highlight barriers to further progress – was launched in the Houses of Parliament.

JDRF clearly needed to have its funded scientists engage with and learn from researchers working on other autoimmune conditions and/or other fields.

To that end, the charity joined Arthritis UK, the Medical Research Council and the Wellcome Trust to host the Grand Challenges in Autoimmune Diseases workshop.

Similarly, the artificial pancreas technology wouldn’t have happened if it wasn’t for researchers that worked on insulin pumps and continuous glucose monitoring coming together to close the loop.

 

Unflagging support

In the UK, the Lord Mayor chose JDRF as a beneficiary charity of this year’s Lord Mayor’s Appeal. This charitable appeal has raised millions of pounds for charities and good causes recommended by successive Lord Mayors in the past.

A lot of people around the world also provided support to JDRF to move projects along through direct funding or fundraising efforts.

Individuals who ru, swim, walk miles and do countless other things to raise funds to support type 1 diabetes research have made and are still making a difference.

The Walk to Cure Diabetes event and the London marathon continue to be the biggest fundraisers, with sums in the hundreds of thousands of pounds collected each year.

According to the most recent estimations provided at JDRF’s anniversary event, a total of £6,100,673 has been raised this year to go towards paying for future trials and developments in type 1 diabetes research.

Thanks to a year on year increase in income over the last three decades, JDRF has funded work towards several life-changing new type 1 diabetes treatments.

 

JDRF 30th Anniversary Dinner, Guildhall, London. Byline John Nguyen/JNVisuals 27/10/2016
HRH The Duchess of Cornwall with JDRF UK CEO Karen Addington. John Nguyen/JNVisuals

 

T1D funded research under development

In the UK alone, in 2006, seven new research projects that held promise to lessen the daily burden of insulin injections and finger-prick testing were awarded funding.

These have included new insulin pumps, artificial pancreas technologies, and latest generation flash blood glucose-reading devices that are gaining massive popularity.

In addition to those better tools that are becoming more readily available, promising scientific advances to modify the disease and improve outcomes are made all the time by immunology experts and endocrinologists:

 

  • Control algorithms

Dr Roman Hovorka, at the University of Cambridge, who receives help from JDRF, has been a major contributor in developing control algorithms, like the one automating insulin delivery that lies at the heart of the artificial pancreas system.

As mentioned earlier, there is an algorithm in the artificial pancreas that closes the loop between existing insulin pump and sensor technologies.

Once glucose levels are measured with CGM, the information is transmitted to the control algorithm, which instructs an insulin pump to release the required amount of insulin into the body.

As a member of the JDRF’s Artificial Pancreas Consortium, Hovorka currently leads the development and testing of the artificial pancreas in type 1 diabetes adults and children.

 

  •  Stem cell regeneration

There’s been substantial JDRF-funded progress in clinical research in 2014, with Dr Doug Melton who was able to produce functional insulin-producing beta cells from stem cells, efficiently and in large quantities*.

(*Since the publication of this article, Douglas Melton and his colleagues at Harvard had to retract a paper about this breakthrough, after no one (including them) was able to replicate the findings).

And, the development of concepts known as macroencapsulation and nano-encapsulation seems likely to build upon Melton’s work and help develop working islet cells in the body.

Macroencapsulation consists in implanting insulin-producing stem cells while protecting them from the immune system thanks to a physical device, called Encaptra, while nano-encapsulation uses a thin protecting coating for the new cells.

 

  • Genetic disease mapping

The study of the genetics of type 1 is also in full swing, and perhaps one of the most funded project in JDRF’s pipeline.

We now know more than 50 genes that influence the risk of developing type 1. We know that some variations of these genes make it very likely someone will develop type 1, while others only increase risk slightly on their ow, but in combination with others could play a much more significant role.

Professor John Todd, who leads the JDRF Wellcome Trust Diabetes and Inflammation Laboratory with Linda Wicker was awarded funding back in 1998 to map and identify the genes contributing to type 1 diabetes in Finnish families, as Finland at the time was thought to be the country with the highest incidence of type 1 diabetes in the world.

Todd has identified a number of gene changes that seem to increase a person’s risk of developing type 1 and his major effort is now to correlate these genetic predispositions with effects on specific type 1 diabetes biomarkers.

 

  • Autoimmunity mediation

JDRF also funded Professor Mark Peakman from King’s College London for his research on the role of T-cells (a subtype of white blood cells) in the inflammation of pancreatic islets(called insulitis) leading to beta cell destruction in type 1 diabetes.

He is currently looking into understanding immune pathways behind this process to develop new therapeutic approaches that could maximise preservation of beta cells.

This is the subject of intense investigation overseas as well, with gerontologists (researchers interested in the aging process) like Dr Valter Longo making very interesting discoveries on the use of dietary interventions to suppress the immune response in certain autoimmune diseases.

A diet mimicking fasting, in particular, has been found in mice and humans to promote regeneration and reduce autoimmunity in multiple sclerosis, which researchers know shares some risk factors with type 1 diabetes.

Researchers found that autoimmune cells died and were replaced by new immune cells, and also that inflammation goes down. Specifically, the mice had reduced levels of pro-inflammatory cytokines known as Th1, which are through to directly mediate beta cell death.

Provided it’s fully clinically tested in more trials involving type 1 diabetes patients, fasting, which seems to have some potential in getting rid of damaged cells and replacing them with new fully functional ones, could in the coming years prove to be a very powerful metabolic therapy in addition to medical treatment.

 

  • Glucose responsive insulins

Glucose responsive “smart insulin” (GRI) is another promising field of research. Researchers are conducting human trials to see if this next-generation insulin could reliably work in response to blood glucose.

All of the smart insulin projects underway are at a very early stage: one (Merck’s MK-2640) is in its first study in humans, and the others are all still being tested in animals.

JDRF, along with Sanofi and the ADA Pathways Program, has given out a lot of support to keep these projects moving forward. The US-based company SmartCells, which was acquired by Merck back in 2011 for the development of their GRI, was funded by JDRF.

Although the perfect smart insulin is still in its infancy, the benefits for people with diabetes on insulin would be very compelling: one injection per day, blood sugar levels that stay in zone without dramatic hypers or hypos, no more carb counting or correct dosage guesswork.

However, like many other technologies and systems, development will likely proceed in steps and the first generation of these drugs or therapies may offer somen, but not all, of the anticipated benefits.

 

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JDRF’s draft set of characteristics for the “ideal” vs. “first-generation” GRI

 

The road to a cure

The artificial pancreas is not the end of the game for JDRF, there is still a lot to be done to help bring to market other revolutionary systems and, ultimately, find a cure that would completely eliminate the need for such technologies.

Until then, the Medtronic system is a most remarkable beginning that will transform the lives of people with uncontrolled type 1 diabetes.

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