Cyclosporine Lansoprazole drug combination was identified as a Practical Cure project in our State of the Cure 2014 report. The Cyclosporine Lansoprazole trial aims to regenerate pancreatic beta cells as well as lower the body’s autoimmune attack on these newly formed beta cells.
We look forward to seeing the results as they start trials in 2015. The following interview with Dr. Levetan shares the details of Perle Biosciences T1D project.
Cara Murphy: How did you and your team get involved in type 1 diabetes research?
Dr. Claresa Levetan: When I was a child (50 years ago), my mother’s best friend had type 1 diabetes. I saw this vibrant, active woman in her 20s and 30s, become blind, go on dialysis, require a seeing eye dog and succumb to the disease. Looking back, this must have been in my mind somewhere.
CM: Please describe to us non-scientists what Perle Bioscience does.
CL: Based on the discovery of insulin and work of the time of Frederick Banting, in which surgeons tied off the pancreas, in order to see improvements in type 1 diabetes, it has been well known that sudden injury to pancreas results in the expression of genes in an attempt to preserve the pancreas. Almost a century ago, “the regenerative powers of the pancreas were well known.” (Here is an article on children for whom pancreatic ligation was a temporarily success option prior to insulin–they didn’t realize that over time there would be autoimmune destruction of new beta cells).
When the human genome became available, many scientific teams, were able to show what genes are expressed to regenerate the pancreas in times of acute injury using rodent models. Our team was able to find the corresponding gene in humans and the bioactive regions of the genes expressed when the type 1 occurs. We were able to show that this therapy can transform pancreatic ducts into new islets containing new pools of beta cells.
CM: How many years have you been on this journey and what keeps you going?
CL: My first job in diabetes was in 1984. I was Chief of Endocrine at Drexel College of Medicine (A merger of Medical College of Pennsylvania (MCP) and Hahnemann Medical School) in Philadelphia. When MCP Hospital closed, I realized it was an opportunity for me to move research faster outside of being at an academic center and co-founded CureDM. When our first regeneration therapy was licensed to Sanofi in 2010 and the research moved in a type 2 direction because there was no model for using a regeneration therapy with an immune therapy, I founded Perle Bioscience in 2012 with a sole focus on type 1 diabetes. We are currently collaborating with many scientists around the world including Yale University to test our Perle’s new regenerative therapies for transforming one’s own pancreatic ductal tissue to islets.
I see type 1 patients every day and work with a fabulous team of people, all of whom have a direct connection to type 1 diabetes–so it is easy to keep going. I am on a mission.
CM: What are 3 things about your project that you want the type 1 diabetes community to know?
CL: 1) We are solely committed to type 1 diabetes
2) We are open to each and every new discovery in the field, whether we make it or not
3) We believe the data to date in the field of type 1 demonstrates that type 1 is not only a disease of autoimmunity, but in man, unlike mice, type 1 is also a disease in which there is lack of beta cell regeneration, even when immune therapy is used.
Thus, we believe that type 1 should be redefined as disease of 1) autoimmunity and 2) lack of beta regeneration. This is likely why there are more than 300 therapies that reverse type 1 in mice and none in man.
4) Our data shows that there are plenty of progenitor cells, even in type 1 patients, to generate new islets–but the newly generated islets that contain new populations of beta cells need to be protected from autoimmune attack.
5) Our team’s approach is for patients to make their own new islets and protect them from immune attack.
CM: If successful, how will it change the lives of people living with T1D?
CL: Our goal is insulin independence among patients with T1D.
Preliminary data has shown that the regenerative therapy can increase stimulated c-peptide by 27% among type 1 patients who have had diabetes for 20 years and little, if any, baseline insulin of their own. Such treatment, when combined with an immune agent could result in insulin independence for new and existing type 1 patients. That is our goal.
CM: In what stage of human trials is your project? When can we expect to learn the next set of results?
CL: We are awaiting FDA approval to start a phase 3 trial with an FDA approved immune therapy and an FDA approved therapy that increases a hormone called gastrin, which is associated with islet neogenesis.
We plan to start studies in Europe as we await FDA approval in the US. Perle is developing more potent regeneration therapies as we demonstrate that the platform of an immune agent with a regeneration agent can result in insulin independence among new onset type 1 diabetes patients.
CM: Are you still recruiting for the trial? If so, how can people get in touch with you?
You can also sign up to follow Perle and my blog through:
CM: What are the biggest obstacles your team faces?
CL: I believe that all obstacles are opportunities, so I don’t see any!
CM: What can the type 1 diabetes community do to support your project?
CL: 1) Make the public–including doctors aware that insulin is a treatment and hardly a cure.
2) Make doctors, including endocrinologists aware that beta cells are not synonymous with islets. Islets contain 5 cell types making 6 hormones—all required for normal glucose. Beta cells make insulin and amylin, critical to life, but the other hormones need to work together with the beta cells. In man, more than 70% of beta cells are actually physically in touch with the alpha, gamma, delta, epsilon and pancreatic polypeptide cells within the islet (see attached article). Among patients without diabetes, 95% of their glucose levels are below 120 mg/dL
3) Visit our blog and talk to us. We are here to listen to scientists and patients and families and friends of patients with type 1.