How DiogenX Plans to Regenerate Your Beta Cells

Imagine a treatment that instructed your body to regenerate healthy new beta cells. DiogenX, a startup biotech firm based in France, is devoted to the possibility.

Type 1 diabetes is defined by the destruction of beta cells by the autoimmune system. Beta cells, found in the pancreas, are the parts of the body that secrete insulin to help keep your blood sugar levels properly balanced. Once a beta cell stops working, it is not replaced. With one intriguing exception, the human body does not create new beta cells after early childhood. You were born with just about every beta cell you’re ever likely to have.

DiogenX thinks it may have cracked the code that can tell your body to create new beta cells. The company, the brainchild of biochemist Patrick Collombat, PhD, has identified a protein that could flip your beta cells back into the regeneration mode they experienced when you were in your mother’s womb. If this protein can be synthesized into a safe medicine, it could represent a way for people with type 1 diabetes to create their own new beta cells, reducing or possibly even eliminating the need for insulin injections.

The company recently secured $30 million to help develop its experimental treatment and fund its first round of human trials. To better understand the treatment’s potential, Diabetes Daily spoke to Katie Ellias, managing director of the JDRF T1D Fund, which has invested in DiogenX. Ellias’ organization invests charitable donations in small private companies “with a focus on a cure for type 1 diabetes.”

Regenerating Beta Cells

Ellias explained, “Beta cells do not naturally regenerate outside of the period when the pancreas is formed in the embryo. It’s not a self-replenishing tissue.” There is very little turnover in your beta cell population.

Your beta cells, like neurons, are supposed to last for your entire life. When diabetes leads directly to beta cell death or incapacitation — whether from the autoimmune attack associated with type 1 diabetes or the escalating insulin resistance associated with type 2 — the body does not replace the lost cells.

There is one incredible exception to this, which suggests that the human body is actually still capable of beta cell replication well into adulthood. “During pregnancy, we sometimes see some new beta cells being produced [by the mother]. There’s an expansion of beta cells to help support the fetus.”

“There’s an idea that we can coax the pancreas back into a regenerative mode.”

DiogenX’s discovery is a protein that instructs the beta cells to self-replicate, just as they did before you were born. The protein modulates “the Wnt/β-catenin signaling pathway, a mechanism that puts the breaks on replication. If you’re able to release the breaks on this mechanism, you can actually see replication of a cell type that wouldn’t normally reproduce.”

The result is easy to understand: new beta cells and more insulin production. In experiments on rodents, DiogenX has been able to both prevent and reverse diabetes. If it works in people, this therapy could reduce or eliminate reliance on exogenous insulin.

Now DiogenX’s task, in Ellias’ words, is “to pick which version of this protein is going to become a drug.” The laboratory is engineering multiple recombinant versions of the natural human protein and evaluating which should be used in the first tests in humans.

The Details

There is still a lot to be learned about DiogenX’s potentially revolutionary therapy. We don’t yet know if the new medication can cause a “stunned” or “sleeping” beta cell to produce a new and fully functional beta cell, or if it requires a reservoir of healthy cells that are still able to secrete insulin.

Ellias says that the therapy “may require you to have some residual beta cells left, but it’s unclear how many left you need to have.” The therapy will likely be first tested in newly diagnosed patients, some of whom have only lost about half of their beta cells to the disease.

But that doesn’t mean that people that were diagnosed years or even decades ago would be out of luck. Even some people with diabetes of an extreme duration retain small but measurable numbers of beta cells that are actively producing insulin.

Another major unknown is how the regenerated beta cells will interact with the immune system that caused type 1 diabetes in the first place. DiogenX’s medication may or may not need to be combined with immunosuppressive therapy. Immunosuppression has been a stumbling block for the leading beta cell transplantation therapies, though DiogenX may have a leg up because it would supplement pancreases with natural endogenous beta cells, as opposed to cells grown in a lab.

“The idea that you could regenerate those cells exactly where they’re supposed to be, without surgery, is very exciting.”

The protein will likely be administered as an injection, ideally a subcutaneous injection like insulin.

“We imagine that it would be initially dosed weekly, whether that’s a few weeks or several months, to get everything going and build up that new population of beta cells. Then we would follow with some periodic maintenance dosing over time.”

But as of yet, this dosing schedule is entirely speculative. Human trials are needed to learn more. To be clear, DiogenX is still only at the very beginning of the process. Even if all goes according to plan, it will take years — and many more millions of dollars — to bring a new treatment to market.

“Our goal is to have this being tested in people with type 1 diabetes in a couple of years.”

“It’s not crazy to think that if this is a real breakthrough, we could get an accelerated review from the FDA. But we’re still at least five to 10 years away.”

Cures, Plural

Little causes as much consternation in the type 1 diabetes community as fallacious promises of a cure. We are painfully aware that people have been told that a cure was “five years away” for decades, probably as far back as anyone could remember.

In 2022, the first type 1 diabetes patient in the world to receive a transplant of laboratory-produced islet cells stopped taking insulin injections entirely. The New York Times and other outlets suggested that it might be a “cure,” but some people in the diabetes community were skeptical, given the patient’s ongoing need for immunosuppressive therapy and questions over how long the transplanted islet cells would stay healthy.

While Ellias believes that DiogenX’s innovation may be “a huge piece” of a therapy that could confer sustainable insulin independence, “We don’t know yet if this therapy can do it by itself, or if it needs to be combined with a therapy for the immune system. How quickly do those newly minted beta cells get killed off by the immune system? We don’t know.”

The treatment could also be combined with a beta cell replacement therapy, boosting transplanted beta cells and causing them to replicate.

“We believe it could be a really exciting disease-modifying therapy that can totally change the course of the disease for someone with type 1 diabetes, but it’s too early to say how it will work with other therapies,” she says.

In truth, Ellias is doubtful that there ever will be a single universal “cure” for type 1 diabetes.

“Ultimately, we believe that there will be a range of therapies that will potentially be used in combination, different therapies for different patients at different ages and disease stages.”

The JDRF T1D Fund is hedging its bets by investing in many different investigative therapies — DiogenX is just one of the startups devoted to the science of beta cells that the fund has supported. Other labs, for example, hope to convert other cells (like alpha cells, which regenerate naturally) into insulin-producing cells, or grow new beta cells in a laboratory.

Eventually, DiogenX will need even more money, likely from one of the major international pharmaceutical companies, in order to complete the type of large and expensive trials required for U.S. Food and Drug Administration approval. Eli Lilly, one of the big three insulin manufacturers, is already an investor. If DiogenX hits the big time, Ellias’ JDRF T1D Fund will redeploy its profits to invest in other startups looking to cure type 1 diabetes from new angles.

“We don’t know what the answer is yet,” Ellias says. “We’re after cures, plural.”

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