Interesting new mouse study - HIP (human proislet peptide)

I know I said that I’d do more research briefs . . . the glorious life of a first year associate; if it isn’t legal research, then who has time for it?

Something did catch my eye this AM, however, that I wanted to post quickly, and since I’m in a good mood, I won’t even bill TuDiabetes in six minute increments for it!

A company named CureDM ( announced yesterday that its product HIP (Human proIslet Peptide) seems to actually work in preclinical studies (read: mice), causing a three-fold increase in the number of islets and functionally curing diabetes, and has also been shown to stimulate islet neogenesis (growth) in human pancreatic ductal tissue that had no islets.

If this works as advertised once it gets into humans, then there are two possibilities that look good for T1 treatment. One is that, by itself and administered with some regularity, it might be possible to outstrip islet death rates - filling the leaky bucket faster than it can drain, as it were. The other possibility is that, coupled with another compound that attenuates the autoimmune response, complete or substantial reversal of T1 might be achieved.

The firm also alleges that T2s also suffer from significant loss of islet cells, and that this might be useful for them as well. I don’t know enough to support or deny that proposition.

Standard caveats about in vitro and mouse testing apply, of course.

I wonder if mice newspapers have headlines like:
“Mysterious Figures in White Labcoats Cure ANOTHER Litter of Diabetics in Pennsylvania”

I think someday mice will be free from disease and they will take over, starting with cats…

Don’t worry, our cat is in strenuous training for just that eventuality, though she might have to divert her attention from her cold war with the pigeons outside our apartment window!

Hi I am the lead author of the study on HIP. My goal in life is to get my patients with type 1 diabetes off of insulin. HIP is part of a human gene and we did show that in human pancreati tissue, we got 5-6 folf more islet generated from pancreati ductal tissue that has now islets–but do contain progenitor cells (more developed than stem cells) and can be turned into islets with HIP.

I have spent the last 5 years on the lab. I promised one of my patients, now 7 years old, Louis Cocco that I would get him off insulin before he is a grownup and that is what I have as my sole and soul’s goal in life. Louis is very special, but with severe neuropathy and retinal issues. I sent him to the best endos I know and to Joslin, with few options given to him.

Several companies have great immune tolerance agents (Diamyd --my favorite with the GAD vaccine), Tolerrx (now with GSK with their anti-CD3 antibody) and Lilly with Kevan Herold anti-CD3 antibody-all of which show immune protection to the pancreas for at least 2 years, but none able to get patients off insulin. In the words of Kevan Herold, “making peace with the immune system is not enough.”

4-celled islets containing alpha, beta, gamma delta cells, are predominately generated during fetal development. After fetal development, it is the beta cells, which have the ability to expand to expand or contract in number based upon the individual. If you look at nondiabetic patient’s islets, thin people have very few beta cells compared to heavier people.

Unfortunately, in type 1 diabetes, there is not only autoimmune attack on the beta cells, but the result in malfunctioning alpha cells and the result if early islet death and reduction in numbers of total islets.
All four cell types are needed for glucose regulation.

Our groups hypothesis, based on work of Lois Jovanovic, in which about a third of type 1 women make normal levels of insulin by the 10th week of pregnancy and some even come off insulin, is that it can take as little as 10 weeks to restore about a million new islets in the right environment. During pregnancy, there is both 1) Down-regulation of immune system so the mother doesn’t reject her fetus as foreign-this down-regulation is likely protecting the beta cells and 2) based on animal models, we know that there is upregulation of the Reg gene, and pregnancy is one of the few times post-nasally, in which new islets are formed.

Thus, a combination of pretreatment with an immune tolerance agent followed by therapy with the bioactive region of the Human Reg3a gene could result in being insulin free in about 3 months. I ask that you read about our team’s work. Dr. Camillo Ricordi will be beginning studies with our peptide shortly in human pancreatic tissue.

I welcome your feedback. I have no other goal in my lifetime, but to keep my promise to Louis.

Most Sincerely,

Claresa (Resa) Levetan, MD

Wow, you are one dedicated, intelligent woman. I am more thankful than you can possibly imagine that people such as you are out there applying your best talents to cure my disease.

Fascinating topic. I find so many of the topics like this look like they could complement each other and how long it will take to get all the individual pieces put together into a cure-package. It seems like it will take several components: Pancreatic cell regen, immune response blockage, nice marketable packaging. the FDA, Clinical trails… I’d be willing to help with that

Of course, Melissa made me think of the old Pinky and the Brain cartoon. “Uh Brain what are we going to do tonight?” “The same thing we do every night, Pinky, break out of our cages and take over the world!” … lol

Best of luck. A cure is something we could all use.

My sincerest thanks! I hope and plan for my team to get you off insulin!
The encouragement always helps!
Claresa Levetan, MD

My thanks!!! I’m working day and night to get you off insulin!
Claresa Levetan, MD

Love your help. What do you think of the name, pancreate? Thanks for your encouragement!
Claresa Levetan, MD