As I often present to colleagues in the field of diabetes, there is a great deal of novelty and interest when I speak of one’s own pancreas regenerating and making new islets. Many shake their heads in disbelief. Ironically, Dr. De Takats said in the early 1900s, “the regenerative powers of the pancreas have been established by many clinical observations.” Dr. De Takats was famous for surgically operating on patients with type 1 diabetes prior to the availability of insulin. Dr. De Takats tied off the tail of the pancreas where most of the islets are, with result of regeneration of new islets. What was not known at the time was that type 1 diabetes was an autoimmune disease. It was not known that those brand new beta cells within newly formed islets are seen by the immune system as foreign and the immune system attacks the beta cells, which ultimately leads to death of the entire islet.
Decades later, many scientists demonstrated that by tying off the pancreas, new islets do indeed form. The trigger of acute injury stimulates the body’s regenerative powers and actual Regenerative Genes to transform pancreatic ducts into islets.
Dr. Lawrence Rosenberg and Aaron Vinik conducted phase 2 B human trials among patients with a 20 year history of type 1 diabetes with no detectable baseline C-peptide (a marker for one’s own internal production of insulin). Dr. Rosenberg and Vinik found that by day 56, type 1 patients had a 27% rise in C-peptide that was statistically significant by scientific standards based on 63 patients in the study. Unfortunately, many of the patients receiving the Reg had a rise in their GAD antibodies indicating an immune attack against new beta cells, and no immune agent was used in the study to protect the new beta cells.
Similar to islet transplants, we hypothesize that an immune agent is needed if one’s own pancreas makes new beta cells. The best example of this is even with an identical twin with type 1 diabetes is given a pancreas from his unaffected sibling without diabetes, the immune attack begins within weeks of transplantation and rapidly progresses to destruction of the beta cells leading to complete islet loss.
What have we learned from more than 300 studies in type 1 diabetic mouse models that have restored glucose levels to normal, with none having done the same in man? Our team has explored in great detail the difference between islets of mice and men and why in man for which there are big differences.
In the picture below, the red cells on the left and right are beta cells; the green cells are alpha cells which make glucagon; and the blue cells are delta cells making somatostatin. In man 70% of the beta cells are directly in contact with the other cell types. The black holes in the human islet are large blood vessels which are innervated by the nervous system—very different from the mouse. This is why if person slams on the brakes of his car or sees a mouse, his or her blood sugar rises in response. This doesn’t happen when a mouse sees a man.
Another difference to note is that in man, islets require 20% of the blood flow of the pancreas, despite being only 2% of the cells. We hypothesize that islets can only live in the pancreas and beta cells can only live in an islet. This hypothesis helps explain why islet transplants have not been as successful as hoped, because the islets of islet transplants landed in the liver, not the pancreas. Data shows that we can make new islets in the pancreas from cells that are already there, even after 20 years or more of type 1 diabetes.
We hypothesize that type 1 diabetes is not only a disease of autoimmunity, but also the inability to resurrect new insulin producing cells. Thus we hypothesize that insulin independence for type 1 requires both an immune agent and a regeneration agent. Keep in mind that many in scientific community still doubt such a thing as a type 1 regeneration agent exists, even though there is evidence of regeneration since Dr. De Takats in the early 1900’s and proof since Drs. Rosenberg and Vinik in 1983. Here’s Perle’s plan.
The immune agent cyclosporine A resulted in up to a 50% remission rate at 1 year among new onset type 1 patients without kidney problems. Unfortunately insulin independence didn’t last and the remaining beta cells existing when the cyclosporine was started, dwindled down until insulin was again required. All pateints stopping cyclosporine did so when they required insulin again, not because of toxicity from cyclosporine, since much lower dosages were found effective to result in insulin independence than used for organ transplants. A recent report even indicated that cyclosporine was superior to tacrolimus in an islet transplant patient whose transplant failed to make insulin and when cyclosporine was added and tacrolimus immune therapy taken away, the transplant worked again and resulted in insulin independence.
Dr. Rosenberg and Vinik’s Reg peptide resulted in a 27% rise in new insulin without an immune agent in those with type 1 diabetes for 20 years. Perle is giving an immune agent with a regeneration agent. We have much data that regeneration therapy works.
In science, anecdotes don’t count, but this is at least worthy of mention. A physician, whose son was recently diagnosed with diabetes, did some extensive reading and tried a combination regeneration therapy and immune therapy. His son is down from 47 units to 2 units per day. Of course, scientists ask, is this coincidence or a honeymoon period? In science, we must be skeptical. We must keep asking questions. We must keep looking at the data. That is what Perle has done, and that is what you must do, even if you are not a scientist. Clinical trials will give us the answer if 1+1=3 when it comes to type 1 diabetes. Neither immune therapy alone nor regeneration therapy alone has sustained insulin independence. We will find out what happens together.
At Perle, we work on developing the most potent regeneration agents and work with immunologists and endocrinologists who help us choose the safest and most effective immune agents.I pray for the day that I write,
Perle Proved It!