Phase 1 Study Shows Promising Results In Type 1 Diabetes

[Ellen]

Phase 1 Study Shows Promising Results In Type 1 Diabetes - Health News Story - WTAE Pittsburgh (http://www.thepittsburghchannel.com/health/16265215/detail.html)

Phase 1 Study Shows Promising Results In Type 1 Diabetes


POSTED: 5:04 pm EDT May 14, 2008
UPDATED: 5:53 pm EDT May 14, 2008

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The following is a transcript of a report by medical editor Marilyn Brooks that first aired May 14, 2008, on WTAE Channel 4 Action News at 5 p.m.

Researchers at Children's Hospital might have a way to reverse type 1, or insulin dependent, diabetes. [URL="http://ad.doubleclick.net/jump/ibs.pit.health/national;kw=health+square+16265215;ad=true;pgtype= detail;tile=8;sz=300x250;ord=123456789?"] (http://ad.doubleclick.net/click;h=v8/36c2/0/0/%2a/y;169575583;0-0;0;12662078;4307-300/250;24160406/24178259/1;;~okv=;kw=health%20square%2016265215%20C05503_10 394%20C05503_10396;comp=202245211;ad=true;pgtype=d etail;tile=4;sz=300x250;~aopt=2/2/78/0;~sscs=%3fhttp://allcaredent.com/)
The treatment cures mice and has not moved on to human trials.
The treatment is for people who have just developed the disease. It is so promising that TrialNet, a national network of diabetes research institutions, has agreed to a national trial using the approach to test for safety. If it proves safe, they'll move on to Phase 2.
Two weeks ago, the mice had type 1 diabetes. They were cured by a treatment that reverses the condition in new onset patients. It begins with leukophoresis.
"Leukophoresis is just to extract the white cells, giving back to the patient the red, the serum and everything," said Dr. Massimo Trucco. "When we have just the white cells, we grow in our petri dish until we have a sufficient number."
Those cells are then treated and returned to the patient with the ability to block the immune system’s attack on insulin-producing beta cells in the pancreas.
"When we will do the real therapy to do to children that still have some insulin-producing cells and are young enough to produce new beta cells," said Trucco.
Leukophoresis is tough on small children. In anticipation of larger human trials, one researcher developed a microsphere-based vaccine to make the process easier.
"They will still need an injection very close to the site where the pancreas is, but it will be under the skin injection, very safe, and it's no different than doing an allergy test," said Dr. Nick Giannoukakis.
Before that therapy is offered, it must be proven safe.
Ryan Cupps, 19, is the first of 14 volunteers in the Phase 1 trial.
"I was excited," he said. "I mean, over 20 million people have diabetes. If I can help those 20 million people, then I'm going to do it."
Cupps was diagnosed with type 1 diabetes in 2000. He takes six insulin injections every day.
Again, the findings of the Phase 1 study shows the vaccine prevents and reverses new onset diabetes in mice. The early human trials are expected to be finished by the end of the year. Trucco expects to be able to move into the Phase 2 study next year.

[DustinsDad]

Fingers crossed and anxiously waiting the long wait. . .

Is this related to Dr Faustman's work?

[CDoyle1013]

This is not related to Faustman. It is out of Pittsburgh with Dr. Trucco who was also using a special dendritic cell to "cure" diabetes...wonder what ever happened to that research...never could find follow ups. I think this research is more akin to Dr. Burt's research out of Northwestern University and conducted in Brazil where he took the immune systems of young people down to nothing after he withdrew blood and cleaned up the blood and redeposited back into the subjects' bodies. This helped restore the immune system. (Not too scientific in explaining, am I?)...I am really glad that so many researchers can cure "new onset" diabetic mice. My daughter does not have much, if any, beta cell function as many who don't have much, if any beta cell function who have been diabetic for more than 3 years. Beta cell rejuvination from the diabetic is a long way off, if any, for her, in my opinion. I hope researchers don't forget people like my daughter. (new onsets still retain beta cell function - just less of them which are constantly being destroyed until all are gone)

[danismom79]

I was just wondering what had become of this research. I haven't clicked the link yet, but does it say anything about how they determine newly diagnosed? Do they test for antibodies and/or beta cells first? The procedure sounds painful and lengthy.

[Pavlos]

I'm very proud a leading researcher in this approach is a fellow Greek, Nick Gianoukakis :D

[DadCares]

Below were some notes I saved from the past (May 06 and May 07) regarding Dr. Trucco. Note that this phase 1 trial had been planned for patients with type 1 diabetes for over 5 years. Has the phase 1 trial been completed? According to my notes, the phase 1 trial was going to start in 07 and be finished by May 2008 (as in now).

03/06 - Thfpe U.S. FDA approved the start of a clinical trial (Phase 1 trial to begin sometime this spring and will include at least 15 patients over the age of 18, who have had type 1 diabetes for over 5 years. Uses strategy from a mouse… observed marked amelioration of diabetes in a mouse model by a novel treatment strategy involving specific modification of the animal’s own dendritic cells. Once harvested, researchers then combine the dendritic cells with specific blockers of molecules, known as CD40, CD80 and CD86, all of which can be synthesized in a laboratory. This treatment strategy was found to inhibit the interaction and destructive effect of T cells. “We did this in mice, giving them six injections over the course of several weeks. The injections interrupted the T cell and beta cell interaction, allowing the beta cells in the pancreas to regenerate. In addition, Dr. Trucco and his team want to combine the dendritic cells with small portions (i.e. peptides) of insulin. Dr. Trucco believes that adding small doses of insulin to the dendritic cells will help guide the dendritic cells directly to the T cells. Adding the insulin ensures the dendritic cells are used specifically to block the T cell destruction of the beta cells, and not otherwise interrupt a person’s immunity.

03/07 – http://clinicaltrials.gov/show/NCT00445913
We propose to ascertain the safety of autologous dendritic cells treated ex vivo with antisense oligonucleotides targeting the primary transcripts of the CD40, CD80 and CD86 co-stimulatory molecules (we term these cells "immunoregulatory dendritic cells; iDC). Study start: March 2007; Expected completion: May 2008, Fifteen (15) individuals exhibiting fully-established, insulin-dependent type 1 diabetics, without any diabetes-related complications, infectious disease, or other medical anomaly, will be enrolled to establish safety of the approach. 7/15 volunteers will be administered autologous control dendritic cells and 8/15 will be administered iDC. The study is anticipated to be complete by twelve (12) months.

[liveitxloveit]

I really hope that this works out!

[CDoyle1013]

Thanks for the additional info on Dr. Trucco. Might just call the research facility to find out the status. Just received a nice brochure from JDRF regarding estate planning donations to JDRF. I laughed because I am committed to finding that cure and putting JDRF out of business before I die, so why would I want to establish an estate donation.....(optimistic thinking, on my part, I guess)

[mickdg]

Some additional reading...

http://www.sciencedaily.com/releases/2008/05/080528140233.htm

[DadCares]

It looks like we'll now watch for the terms "microsphere" in the future, which is their follow-up research after the previous research on "dentritic" cells (if I'm reading this correctly).

A couple of items cut and pasted from the article:

scientists injected the microspheres under the skin near the pancreas of mice with autoimmune diabetes. The microspheres were then captured by white blood cells known as dendritic cells which released the nucleic acid molecules within the dendritic cells. The released molecules reprogrammed these cells, and then migrated to the pancreas. There, they turned off the immune system attack on insulin-producing beta cells. Within weeks, the diabetic mice were producing insulin again with reduced blood glucose levels.

The microsphere research builds on previous research by Drs. Giannoukakis and Trucco in which they used dendritic cells delivered to the pancreas in another method to turn off the immune system's attack on insulin-producing beta cells, thereby allowing the cells of the pancreas to recover and begin producing insulin again.

[Garrett's Mom]

Human trial begins on diabetes vaccine
Thursday, May 29, 2008
By David Templeton, Pittsburgh Post-Gazette

Type 1 diabetes has long been difficult to manage with little hope for a cure.
But in a potential breakthrough, Children's Hospital in Pittsburgh has begun human clinical trials to test a vaccine designed to block the autoimmune response that kills insulin-producing beta cells in the pancreas, resulting in Type 1.

Safety trials on the novel method of correcting Type 1 are under way. If the vaccine is deemed safe, the study will enter phase II, to test whether it succeeds in restoring insulin production in children newly diagnosed with Type 1. There's additional hope the process can prevent the disease in people predisposed to develop it and restore some insulin production in those who have had Type 1 for years.

Drs. Massimo Trucco and Nicholas Giannoukakis at Children's Hospital already have proven success in mice. They expect results in human clinical trials in 2010.

If fully successful, the process would require a shot with perhaps an annual booster to prevent T-cells from resuming their attack on beta cells. Insulin is the hormone that allows blood glucose to enter cells and be used as energy. Insulin injections, dietary measures, exercise and blood-glucose monitoring are necessary to prevent high blood glucose levels that prompt heart disease, strokes, kidney failure, blindness and circulation problems that can lead to limb amputations.

Correcting the problems is complex.

The Pitt team uses artificially produced "microspheres," or microscopic containers loaded with nucleic acid. When injected under the skin of mice, the microspheres are swallowed by dendritic cells, or white blood cells, that fight infection. The microspheres release their load of nucleic acid, which prevents the dendritic cells from producing the rogue proteins that signal T-cells to wage an autoimmune attack on beta cells.

The pancreas then can regrow beta cells and produce insulin naturally. How long the beneficial effect will last, if it works at all, has yet to be determined.

Previously, Drs. Trucco and Giannoukakis figured out a more complex method of altering dendritic cells to halt T-cell attacks on beta cells. Use of microspheres simplifies the process and involves only an injection -- rather than a lengthy dialysis type procedure -- to initiate the curative treatment.

"This is a very exciting approach because in many ways it simplifies what the dendritic-cell approach is all about," said Dr. Michael Clare-Salzler, a University of Florida endocrinologist who is doing similar research. "We've been the crazies in left field, but for me it makes ultimate sense.

"Bottom line, this approach is hopeful," he said. "I'm a big fan of Nick and Massimo. They are great scientists and excellent people, and it's great to see them having success."

If the process works in humans, there's concern it might last only a few months. If all goes well, there's hope the process will work with only occasional boosters.

That's the hope of nearly 1 million people in the United States with Type 1, including one in every 400 to 600 children.

"I always said my only dream was to have one patient eat ice cream without feeling guilty," Dr. Trucco said. "If I do that for any child with diabetes, I will feel that I didn't waste my life."

First published on May 29, 2008 at 12:00 am