How DiogenX Plans to Regenerate Your Beta Cells

Imagine the treatment that you instructed your body to regenerate healthy new beta cells. Diogenx, a French-based startup biotechnology company, is dedicated to its potential.

Type 1 diabetes is defined by the destruction of beta cells by the autoimmune system. Beta cells found in the pancreas are parts of the body that secrete insulin to maintain proper balance in blood glucose levels. If the beta cell stops working, it will not be replaced. With one interesting exception, the human body does not create new beta cells after childhood. You were born in almost every beta cell you are likely to have ever had.

Diogenx believes it may have cracked a code that could tell your body to create a new beta cell. The company, the brainchild of biochemist Dr. Patrick Columbat, has identified proteins that can return beta cells to the regeneration mode they experienced while in their mother’s uterus. If this protein can be synthesized into a safe drug, it represents a way for type 1 diabetics to create their own new beta cells, reducing or perhaps even eliminating the need for insulin injections.

The company recently developed an experimental treatment and set aside $30 million to fund the first round of human trials. To better understand the potential of treatment, diabetes spoke to Katie Ellias, managing director of the JDRF T1D fund, who invested in Diogenx daily. Elias’ organization is a venture charity fund that invests in small and medium-sized businesses “focusing on type 1 diabetes treatments.”

Regeneration of beta cells

Elias explained, “Beta cells do not regenerate naturally outside of the era when pancreas form in embryos. It is not self-renewal tissue.” Beta cell populations have very little turnover.

Beta cells like neurons are supposed to last for your life. If diabetes directly leads to beta cell death or incapacity – whether from autoimmune attacks associated with type 1 diabetes or escalated insulin resistance associated with type 2, the body is not a replacement for lost cells.

There is one incredible exception to this. This suggests that the human body is still capable of replication of beta cells until adulthood. “During pregnancy, some new beta cells may be produced (by the mother). There is an expansion of beta cells to support the fetus.”

“There’s an idea that the pancreas can be returned to regeneration mode.”

The discovery of Diogenx is a protein that tells beta cells to self-reply, just like before you were born. Proteins “regulate the Wnt/β-catenin signaling pathway, the mechanism that places breaks in replication. If you can release a break in this mechanism, you can see the replication of cell types that don’t actually reproduce.”

The results are easy to understand: new beta cells and more insulin production. In rodent experiments, Diogenx was able to prevent and reverse diabetes. If it works in people, this therapy may reduce or eliminate dependence on exogenous insulin.

Currently, Diogenx’s task is, in Ellias’s words, “to choose which version of this protein will become the drug.” The lab is engineering multiple recombinant versions of natural human proteins and assessing what needs to be used in initial human tests.

detail

There is still much to learn about Diogenx’s potentially innovative therapies. It remains to be seen whether a new drug can cause “surprising” or “sleep” beta cells to produce new, fully functional beta cells, or if a healthy cell reservoir is needed that can secrete insulin.

Elias said the treatment “needs to have remaining beta cells, but it is unclear how many remaining beta cells are needed.” The treatment may be first tested in newly diagnosed patients, some of which have been lost in only about half of the beta cells in disease.

But that doesn’t mean that people diagnosed years ago are out of luck. Even some of the extreme duration of diabetes retain small but measurable beta cells that are actively producing insulin.

Another major unknown is how regenerative beta cells interact with the immune system that first caused type 1 diabetes. Diogenx medications may or may not need to be combined with immunotherapy. The immune system, in contrast to cells grown in the lab, can replenish the pancreas with natural endogenous beta cells, so diogenx may raise the legs, but the immune system was the stumbling block of prior beta cell transplantation therapy.

“The idea that these cells can be regenerated accurately without surgery is extremely exciting.”

The protein may be administered as an injection. Ideally, it would be a subcutaneous injection like insulin.

“We imagine that whether it’s weeks or months, it’s all done and initially administered weekly to accumulate that new betacell population, whether it’s weeks or months. Then, regular maintenance is done over time.”

However, this dosing schedule is still completely speculative. To learn more, you need a human exam. To be clear, Diogenx is still only at the beginning of the process. Even if everything goes according to plan, bringing new treatment to the market will take years and millions more.

“Our goal is to test this in people with type 1 diabetes in a few years.”

“If this is a real breakthrough, it’s not strange to think we can get accelerated reviews from the FDA. But we’re still at least five to ten years away.”

Treatment, multiple

The type 1 diabetes community is almost as surprising as the false promise of treatment. We are painfully aware that people are saying that treatments are “five years away” for decades, as far as everyone remembers.

In 2022, the world’s first type 1 diabetes patient was completely stopped insulin injections when he received a transplant of laboratory-produced islet cells. New York Times Other outlets also suggested that it could be a “treatment,” but some people in the diabetic community were skeptical given patients’ continued need for immunosuppressive therapy and the questioning of how healthy the transplanted islet cells would maintain.

Elias believes Diogenx’s innovation is a “huge piece” of treatments that can confer sustainable insulin independence, but “whether this therapy can do it on its own, or it needs to be combined with treatments of the immune system, or how quickly those newly created beta cells are killed by the immune system?

Treatment can also be combined with beta cell replacement therapy to increase the transplanted beta cells and replicate them.

“We consider it to be a truly exciting disease therapy that can completely change the course of a person with type 1 diabetes, but it’s too early to say how it works with other treatments,” she says.

In fact, Elias suspects that there is a single universal “treatment” for type 1 diabetes.

“Ultimately, we believe there is a range of treatments that could be used in different combinations of patients at different ages and stages of disease.”

The JDRF T1D fund hedges bets by investing in a variety of research therapies. Diogenx is just one startup dedicated to the science of beta cells that the fund has supported. For example, other labs hope to convert other cells (such as naturally regenerating alpha cells) into insulin-producing cells, or grow new beta cells in the lab.

Ultimately, Diogenx will likely need more money from one of the leading international pharmaceutical companies to complete the types of large and expensive trials needed for approval by the US Food and Drug Administration. Eli Lilly, one of the big three insulin makers, is already an investor. If Diogenx spends a big time, Ellias’ JDRF T1D fund will redeploy its profits to invest in other startups aiming to cure type 1 diabetes from a new angle.

“I don’t know what the answer is yet,” Elias says. “We are in the plural after treatment.”