Whenever I talk about the Human Genome Project as holding the key for insulin independence, whether speaking to endocrinologists or patients, I often get glazed-over stares. Gene therapy sounds like some spooky, complex science with visions of people getting injected with genetic material that would transform them into different creatures. While getting rid of the need to inject insulin would indeed transform the entire person with type 1, our goal is to physically only create new insulin-producing cells within their pancreas.

I was recently told by a colleague, “Resa, gene therapy for diabetes won’t be here for at least 50 years.” My response to this very distinguished pediatric endocrinologist was that I couldn’t disagree more. I am used to crazy stares and shaking of heads, when I say that diabetes gene therapy is here and effective, and we even have randomized, double-blinded studies in type 1 patients to prove that gene therapy can increase one’s own insulin, even if you have had type 1 diabetes for 20 years.

Gene therapy provides the ability to produce new islets of Langerhans from one’s own pancreatic ductal tissue and has been the focus of far too few scientific teams. In contrast, there has been three decades of multiple studies using only an immune therapy approaches among new onset type 1 diabetes, which has not proven to reverse diabetes in man as it does in mice.

Beta cells predominately come from beta cells after fetal development. In type 1 and type 2 diabetes, diabetes results from too few beta cells making too little insulin. New islets formed with gene therapy not only contain beta cells, but also 4 other cell types; each producing different hormones necessary for glucose control.

The concept that new insulin producing islets can form from pancreatic ductal tissue, in contrast to beta cells simply being produced from existing beta cells, was first described in 1893, by the French histologist, Edouard Laguesse when he was looking for how new islets were formed after fetal development . In the early 1900’s, doctors used to tie off the pancreas as a surgical intervention for diabetes, for regrowth of new islets before insulin was available.

We now know that it is during times of acute pancreatic injury that we have found that specific genes are expressed to help heal the pancreas.  These happen to be the same genes present during fetal development with islets are generated for the first time.  Otherwise, these genes are typically only expressed during fetal development when the islets are formed in the pancreas for the first time.

Since the availability of the Human Genome, many scientists in the diabetes field, have gathered blood or saliva swabs to identify, which genes that people with diabetes have in common, and used this information to identify patients who are at high risk for developing, particularly type 1 diabetes, prior to diagnosis. Even though this has resulted in a large amount of predictive data, it has not progressed to any therapies to prevent the onset of type 1 diabetes, in those identified with high risk genes.

Instead of searching for the common genes expressed in diabetes, I searched for the genes necessary to make islets containing new beta cells in utero for the first time when the pancreas is being formed. These are the genes that are healing genes. As it turns out, when the pancreas is injured, these same genes that form the pancreas in utero, pop up to help heal the pancreas. For example, we have found the same gene present when a patient has pancreatitis (inflammation of the pancreas). Our team and other teams have shown that this one specific gene family known as the REG gene transforms pancreatic ductal tissue to new insulin producing islets. We also know that the REG genes signal to form new insulin producing cells.

I was fortunate to be a researcher on the type 1 and 2 studies using an active region of a REG gene that demonstrated a 27% rise in endogenous C-peptide in a randomized, double-blinded controlled trial among type 1 patients who had the disease for 20 years.

This therapy was safe. It required one injection per day and no adverse effects were seen other than at the injection site. The results were profound and demonstrated the ability of the type 1 pancreas that had no insulin production at baseline, to make new insulin within weeks of treatment. The results could not be sustained and were largely discounted, which we now better understand that an immune agent is required to protect the new beta cells from immune attack.

Patients with type 1 diabetes need to protect their new beta cells from immune attack. Just like the immune system fights off a cold by mounting antibodies, the immune system sees the new beta cells as foreign and attacks with a vengeance.   The newly formed beta cells cause the immune system havoc and are the most at risk for the immune attack.

My colleagues may shake their heads and laugh, because I see diabetes pretty simply.  There are not enough beta cells. Whether you have type 1 or type 2, whether you are a child or an adult with diabetes, there is one single problem—you do not have enough beta cells to make enough insulin to bring glucose/sugar out of the bloodstream into cells so the body can use the sugar as energy. When sugar levels remain above normal levels in the blood vessels, over time there is damage resulting in all the too well known complications of diabetes.

These are big problems and require more than insulin. That’s why we are focusing on regenerating entire new islets that make not only insulin, but also amylin, glucagon, somotostatin, pancreatic polypeptide and ghrelin. New insulin producing islets can and do form in patients with type 1 diabetes, even if they have had diabetes for decades. Our team doesn’t make beta cells in a dish or implant donor islets. We make beta cells using the bioactive portion of a REG gene that makes insulin producing islets from one’s own pancreatic ductal tissue.

Yes, you can make your own new islets from your own pancreatic ductal tissue, even if you have had diabetes for 20 years. We are working on an oral pill that is targeted to pancreas for our REG gene therapy, so we keep to Perle’s commitment to insulin independence and being Needle Free .

HumanDuctalTissue

Gene therapy for diabetes is the only therapy that addresses the underlying problem in diabetes—too few beta cells. At Perle, we are ushering in a new world without diabetes… sooner than believed possible.