Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCLA neuroscience research leads to a possible treatment for type 1 diabetes

19.09.2006
A new vaccine being tested in a human clinical trial holds a great deal of promise for treating type 1 diabetes, a disease that newly afflicts 35,000 children each year. The research that established the foundation for this vaccine was conducted in UCLA research laboratories. The drug is still being tested and is not likely to be available for at least a few years.

"It's the only thing so far that really slows this disease down without adverse side effects," Allan J. Tobin, a UCLA professor emeritus of physiological science and neurology, said about the new drug. "The amazing thing about this emerging story, however, is that it started from basic research on the brain." Tobin, whose laboratory conducted critical neuroscience research in the late 1980s and 1990s, is a member and former director of UCLA's Brain Research Institute.

Type 1 diabetes -- also known as insulin-dependent diabetes or juvenile diabetes (because it usually begins in childhood or adolescence) -- afflicts more than 1 million Americans. It is characterized by a failure of the body to produce insulin because the immune system attacks and destroys the body's insulin-producing cells of the pancreas.

On Sunday, Sept. 17, at a meeting in Copenhagen of the European Association for the Study of Diabetes, Johnny Ludvigsson -- pediatrics professor at Sweden's University Hospital, Linköping University -- will present results from the phase II study conducted in eight hospitals in Sweden in collaboration with Diamyd Medical (www.diamyd.com), a life science company located in Stockholm, Sweden.

This fundamental discovery that influenced thinking about diabetes was made in the Life Sciences Division of UCLA's College of Letters and Science, said Arthur P. Arnold, UCLA professor and chair of physiological science.

"The broad insight of a basic neuroscience team eventually bore fruit in the fight against this disease," Arnold said. In the 1980s, using newly developed recombinant DNA techniques, Tobin's laboratory was studying genes involved in brain development and function. Tobin's team included graduate student Daniel Kaufman, now a UCLA professor in the department of molecular and medical pharmacology, and graduate student Mark Erlander, now executive vice president and chief scientific officer of AviaraDx, a biotechnology company in Carlsbad, Calif.

Together, Kaufman and Erlander were the first to isolate the genes encoding GAD (glutamic acid decarboxylase) which is an important enzyme because it synthesizes one of the main neurotransmitters for communication between neurons. Tobin's laboratory used these tools to study neuronal development in the brain. What no one knew at that time was that GAD was also made in the cells that made insulin in the pancreas -- cells that use the chemical transmitter made by GAD to communicate with other pancreas cells to help control glucose levels in the blood.

A year later, Kaufman's car fortuitously broke down while he was a postdoctoral scholar at the Salk Institute in San Diego, Calif. Forced to wait, he went to the library and stumbled on a report in a medical journal showing a connection between autoimmunity to an unknown protein in insulin-producing cells and diabetes. Kaufman surmised that this unknown protein was in fact GAD, the protein he had studied in Tobin's lab.

To study the possible connection between GAD and diabetes, Kaufman again worked with Tobin and Erlander, using the research tools they had developed to test whether autoantibodies against GAD could be found in frozen blood samples taken from individuals before they developed type 1 diabetes. They found that they could detect autoantibodies against GAD years before the symptoms of diabetes appeared.

In type 1 diabetes, the immune system destroys the insulin-producing cells slowly, over as many as seven years before any symptoms appear, Tobin said. "These tools allowed us to detect the early appearance of an autoimmune reaction more than five years before the onset of diabetes," Tobin said.

Many laboratories throughout the world are now using recombinant GAD to determine whether individuals have autoantibodies to GAD and are likely to develop diabetes. This pre-diagnostic test will be invaluable for preventing diabetes -- but first, there must be a therapeutic to slow the progression of the disease.

In his own laboratory at UCLA, Kaufman, along with UCLA's Jide Tian, Michael Clare-Salzler, Eli Sercarz, Paul Lehmann and Tobin, searched for ways to "tolerize" the immune system of diabetes-prone mice to the GAD protein before the autoimmune attack began. The team reported in the journal Nature in 1993 that when young, diabetes-prone mice were treated with a small amount of the GAD protein, their immune systems learned to tolerate the protein. The autoimmune response that leads to type 1 diabetes never developed in these mice as they grew older.

Next, Kaufman and Tian developed the GAD vaccine that was able to inhibit the autoimmune response after it had already begun to attack the insulin producing cells. Kaufman and Tian showed in a study they published in Nature-Medicine in 1996 that, even after the type 1 diabetes disease process had started in diabetes-prone mice, its progression could be inhibited by the GAD vaccine.

The GAD vaccine activated T-cells that recognized GAD, Kaufman and Tian reported. "The T-cells traveled to the pancreas and, recognizing the GAD protein in the insulin-producing cells there, released calming substances called 'anti-inflammatory' cytokines, which suppressed the immune cells that were killing the insulin-producing cells," Tian explained.

UCLA licensed the technology to Diamyd Medical for clinical development. Tobin and Kaufman both serve on the scientific advisory board of Diamyd.

Based on the success of the GAD vaccine to prevent diabetes in mice, Diamyd Medical conducted a phase II clinical trial by treating adults who recently had been diagnosed with diabetes. The results showed that treatment with the GAD vaccine could preserve some insulin production for at least two years after the onset of the disease in adults.

Given these promising results, Diamyd next conducted a larger double-blind clinical trial of the GAD vaccine in 70 children and adolescents who were newly diagnosed with diabetes. After treating new diabetics with the GAD vaccine, or a placebo, the patients were followed for 15 months, without the clinicians knowing which treatment the patients had received. This month Diamyd Medical broke the code and announced that the GAD vaccine demonstrated statistically significant efficacy in preserving insulin production and that no serious adverse events associated with the therapy were observed.

Tobin and Kaufman are optimistic about the drug, which is called Diamyd, but both said it is likely to be at least a few years before a drug for type 1 diabetes is available.

"If the result holds up in a phase III trial, it's going to make a big difference," Tobin said. "It feels terrific."

"It's tremendously gratifying to see our work go from the lab to a clinical application, with the potential to help so many people," Kaufman said. "The data are very strong, and are convincing even to scientists who were initially skeptical. The vaccine is highly targeted; it activates only the immune cells that recognize GAD, which then suppresses the immune cells that are attacking the insulin-producing cells. Most of us who go into science hope our research will advance medical treatment and improve human lives; it's great news."

He added, "Such long-term preservation of insulin production after the onset of diabetes is quite remarkable. Preserving insulin-production is crucial for delaying the complications associated with long-term diabetes, such as kidney and heart disease, and neuropathy. Now that the vaccine has shown efficacy in preserving insulin production after disease onset, we are anxious to see whether the vaccine can also prevent the development of type 1 diabetes."

The children who are likely to develop type 1 diabetes can be identified by screening for autoantibodies to GAD in their blood, Kaufman said. Tobin, 64, is currently managing director of MRSSI, which advises two nonprofit organizations, the High Q Foundation and CHDI, both dedicated to finding therapies for Huntington's disease. From 1975 to 2003, he was on the faculty of UCLA, where he taught introductory biology and neuroscience. He is the coauthor of "Asking About Life," a prize-winning biology textbook whose premise is that questions are more important than answers.

Tobin's research was funded by the National Institute of Neurological Disorders and Stroke, part of the National Institutes of Health. Kaufman's research is funded by the National Institute of Diabetes & Digestive & Kidney Diseases, also part of part of the National Institutes of Health.

Tobin recalls bringing the excitement of his research into the UCLA classes he taught.

"When I taught the introductory biology course, I said here's the standard stuff about the immune system, but let me tell you about something that just happened in my lab," Tobin recalled. "There's a thrill of discovery, and also a sense that there remain challenges ahead; science isn't just learning a set of facts but learning how to approach and formulate scientific problems. That engagement really serves undergraduates at UCLA very differently from undergraduates at non-research colleges."

As is often true in science, solutions to important problems come from unexpected places, and basic research provides the foundation for future applications.

"Type 1 diabetes never occurred to me," Tobin said. "I was interested in how cells in the brain signal one another. We were trying to understand how some cells in the brain told other cells to slow down or stop.

"One of the great things about UCLA's College of Letters and Science is that scientists working on basic questions talk with one another and with medical school scientists. At first it wasn't obvious that inhibitory signaling in the brain and in the pancreas uses the same molecules, but they do. The diabetes diagnostic and therapeutic came out of basic research in an unpredictable way."

Stuart Wolpert | EurekAlert!
Further information:
http://www.ucla.edu

More articles from Health and Medicine:

nachricht NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures
17.11.2017 | National Institute of Standards and Technology (NIST)

nachricht High speed video recording precisely measures blood cell velocity
15.11.2017 | ITMO University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

NASA detects solar flare pulses at Sun and Earth

17.11.2017 | Physics and Astronomy

NIST scientists discover how to switch liver cancer cell growth from 2-D to 3-D structures

17.11.2017 | Health and Medicine

The importance of biodiversity in forests could increase due to climate change

17.11.2017 | Studies and Analyses

VideoLinks
B2B-VideoLinks
More VideoLinks >>>