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Patrick Collombat: A Cure for Type-1 Diabetes within Reach?

Patrick Collombat has been studying the pancreas for the past 20 years. His sights are set on type-1 diabetes, a form of the disease in which the insulin-producing cells are destroyed. Today, the researcher and his team are pursuing a promising avenue: GABA. This natural substance is thought to enable the safe regeneration of the missing cells. There is real promise of a curative treatment on the horizon...

Have you always been interested in the pathophysiology of diabetes?

Patrick Collombat

Absolutely! I started to look at the function of the pancreas and diabetes in 1999, as part of my PhD thesis research at the Max Planck Institute in Goettingen (Germany). In 2009, I got the opportunity to join the Valrose Biology Institute, in Nice, to set up a dedicated research team there. My objective was to find a way of regenerating pancreatic beta cells. Beta cells are insulin-producing cells that reduce blood sugar levels. These cells are destroyed in patients suffering from type-1 diabetes. And it was in 2009 that we managed to do just that.

What is the mechanism that allows the pancreas to self-regenerate?

As well as beta cells, the organ also contains alpha cells. Alpha cells produce glucagon, which increases blood sugar levels when necessary. These two cell types are structurally quite similar, but we identified a key element setting them apart: the expression of a master gene - Pax4 - in beta cells. When the expression of Pax4 is induced in alpha cells, they turn into beta cells and start producing insulin.

Having observed this effect in mice, we wanted to study the feasibility of such a strategy in humans. It obviously wasn’t possible to use the genetic modification approach we had adopted for mice, so we looked for a substance that would mimic the Pax4 activation effect. Working with several international teams, we sifted through thousands of substances, eventually identifying GABA, a neurotransmitter sometimes used as a food supplement. In mice, it promotes the transformation of alpha cells into beta cells. At the same time, to compensate for the lack of alpha cells, the body produces new ones that are once again converted into beta cells. Overall, the production of new beta cells is continuous but controllable, with no runaway effect.

Is this a promising avenue for humans in the short term?

Yes. We’re going to launch the first therapeutic trial this year. It will evaluate the capacity of GABA to regenerate pancreatic cells in 60 adults suffering from type-1 diabetes. The trial will also allow us to confirm the safety of the substance and determine the most effective dose if it is indeed safe. 

The conclusions of this study will be available in late 2018. They will represent the culmination of almost 10 years of research in which the funding provided by the European Research Council (ERC Starting Grant) has been pivotal. Thanks to the €1.5 million we’ve obtained since 2011, we’ve been able to expand our team. The ERC is also a label of excellence that has enabled us to gain international recognition, forge important partnerships and secure additional funding. It is a virtuous circle that fuels and accelerates new discoveries and ultimately brings hope for all type-1 diabetes patients.

Find out more about Patrick Collombat and his research
Patrick Collombat leads the Genetics of diabetes team within Inserm/CNRS/University of Nice unit 1091, at the Institut de biologie Valrose (Valrose Biology Institute) in Nice.

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