How did a cancer drug lead to a treatment for diabetes?

This story starts with a casual chat between two scientists passing each other in the hallway.

It ends with a revolutionary new treatment for diabetes.

And in-between there’s a new drug which can stop cancer.

How they are connected reveals the way in which scientific research can sometimes yield unexpected results.

But back to the beginning, when Professor Christopher Parish, immunologist and cancer biologist at the ANU John Curtin School of Medical Research, created a brand new anti-cancer drug, which not only stops the spread of cancer but also prevents tumours from growing in the first place.

This cancer drug, called PI-88 (Muparfostat), works by eliminating the activity of an enzyme called heparanase, which allows tumour cells to invade the body’s organs.

You can think of heparanase as Pac-Man, chasing down and eating not ghosts, but a chemical substance, called heparan sulfate, which keeps the tissue barriers, or protective shields, of our bodily organs intact.

This eating-away of the body’s internal protective layers is what allows cancer to spread. So if this is a game of Pac-Man, you’re losing.

It was at this point in his research that Professor Parish walked down a hallway and passed his colleague, Associate Professor Charmaine Simeonovic, a medical researcher specialising in diabetes. He mentioned to her his hunch that loss of heparan sulfate might be one of the big issues in type 1 diabetes too.

When they put this theory to the test, both researchers were surprised to find that the particular cells which are depleted in diabetes—pancreatic insulin-producing cells—had high levels of heparan sulfate.

Similarly to how heparan sulfate is necessary for keeping our organs cancer-free, they realised that heparan sulfate was also necessary to keep these insulin-producing cells healthy and alive.

They also found that in type 1 diabetes, the immune system produces the same enzyme that breaks down tissue barriers in cancer—heparanase, which we know as Pac-Man. In this case, the heparanase leads to the death of insulin-producing pancreatic cells.

This discovery was ground-breaking, because the key problem in type 1 diabetes is that there are not enough insulin-producing cells.

And when it came to shutting down the enzyme that was killing off those insulin-producing cells, the researchers didn’t have to look too far for a solution, because Professor Parish had already developed just that: a cancer drug called Muparfostat that packs a double punch by both inhibiting the enzyme heparanase and replenishing heparan sulfate supplies.

And it worked.

Muparfostat was found to reduce diabetes in mice by 50 per cent, and it is hoped similar results will be true in human patients.

Professor Parish’s anti-cancer drug, Muparfostat, is also in its final stages of testing.

So it’s game-over for Pac-Man, but a huge win for patients.