Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Targeted DNA vaccine may reverse autoimmune disease

11.08.2003


Stanford University Medical Center researchers have developed a way to tailor therapies to combat the specific inappropriate responses of autoimmune diseases in mice. The researchers also have shown that their technique can provide information needed to predict a disease’s progression. Eventually, their work may provide a way to reverse the course of such autoimmune diseases in humans as multiple sclerosis, rheumatoid arthritis and type-1 diabetes by first identifying the immune system culprits gone awry and then creating customized therapies for individual patients.



Researchers Bill Robinson, P. J. Utz and Lawrence Steinman published results last year showing how microarrays - glass slides spotted with minute amounts of the proteins against which the body may be reacting - can provide a profile of the antibodies’ targets. Their current work, which appears in the September issue of Nature Biotechnology, takes the technology a step further and shows that the pattern of antibody activation can be used to predict and treat animals suffering from a disease resembling M.S.

"Ultimately, we think the array can be used to guide patient-specific therapy," said Robinson, MD, PhD, assistant professor of medicine (immunology and rheumatology) and lead author of the study. For example, a blood sample from a patient thought to have M.S. could be profiled using the array to help identify whether the person is likely to progress to full-blown disease and whether the individual would benefit from therapy. The information obtained in the profile could then be used to personalize therapies.


The team, which included former Stanford researcher Hideki Garren, MD, PhD, showed that this strategy works in a mouse model of M.S. called experimental autoimmune encephalomyletis, or EAE. In both conditions, the immune system launches an attack against the myelin sheath, the fatty cells that insulate neurons from electricity and ensure the speedy transmission of nerve impulses. Neurons that have patches of myelin destroyed by M.S. or EAE short-circuit and can lead to a variety of neurological disorders, depending on the part of the brain affected.

"Looking at one M.S. marker at a time had previously not been terribly informative," said Robinson. "We thought that looking at thousands at once would be more fruitful." Thanks to a dozen or so labs around the world that shared their protein samples, the group rapidly produced a comprehensive array that covered hundreds of the myelin sheath proteins.

When they analyzed serum samples from EAE mice using the array, they found that each mouse had a unique pattern of reactivity. Based on their antibody profiles, mice whose immune systems were attacking more elements on the myelin sheath progressed to a more severe disease, while mice whose immune systems made more restricted responses did not progress and had fewer flare-ups. The group then designed a treatment to reverse the progression of the disease, treating mice that had already suffered an initial attack of paralysis.

Autoimmune responses are thought to develop when antibodies attack many different proteins in the organ being targeted, so Robinson and his colleagues wanted to find a therapy that specifically knocked out as many of the harmful responses as possible while leaving the rest of the immune system functional. To do so, they took advantage of a well-known but poorly understood process known as tolerization. In this process, the immune system is coaxed to tolerate an offending protein after injection of that same protein or pieces of it. Utz, MD, assistant professor of medicine (immunology and rheumatology), likens the process to allergy shots: the agent causing the allergic reaction is injected into muscle in order for the body to learn to ignore it.

Using the microarray information to guide them to the targets of the autoimmune response in the sickest mice, Garren and Steinman, MD, professor of neurology and neurological sciences, built on previous studies in Steinman’s lab to create a tolerizing vaccine that delivered four of the targeted proteins. To make an effective delivery vehicle, they put the DNA sequence that encoded the proteins into a circular piece of DNA called a plasmid, creating a DNA vaccine. When these engineered plasmids were injected, they produced the desired proteins and a programmed tolerization process began.

One advantage of DNA vaccines over other methods of tolerization, Garren noted, is that it allows for multiple autoimmune targets to be tolerized simultaneously rather than one at a time. "We found that this approach broadly turns off autoimmune responses," said Robinson. "Clinically, the animals do better when receiving the vaccine. When we use our arrays to monitor the response, we see broad reductions in the progression of the disease."

The ability to profile which antibodies have gone awry has a number of implications for diagnosis and treatment of people with autoimmune diseases. "When we see these patients, we have no idea what is going to happen 10 years from now," Utz said. "It would be great to have a test that would let us know if a person is going to have a horrible outcome so we could treat aggressively, or if a person is going to be fine, or if a person is going to have a bad response to a therapy so we could avoid that."

Led by Steinman, the team plans to use their findings to help people with autoimmune diseases. To reach this goal, they co-founded Bayhill Therapeutics; Garren directs the scientific efforts of the company.

Using DNA vaccines to specifically turn off the immune system is a completely new way to immunize, said Steinman. "This is the opposite of what we try to do with traditional vaccines against bacteria and viruses, where we want to stimulate the immune system to attack the microbe," he added.

This study was funded by a number of sources, including funds from a $14.7 million contract from the National Institutes of Health, the Baxter Foundation and the Arthritis Foundation.

Mitzi Baker | EurekAlert!
Further information:
http://mednews.stanford.edu

More articles from Life Sciences:

nachricht More genes are active in high-performance maize
19.01.2018 | Rheinische Friedrich-Wilhelms-Universität Bonn

nachricht How plants see light
19.01.2018 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Artificial agent designs quantum experiments

On the way to an intelligent laboratory, physicists from Innsbruck and Vienna present an artificial agent that autonomously designs quantum experiments. In initial experiments, the system has independently (re)discovered experimental techniques that are nowadays standard in modern quantum optical laboratories. This shows how machines could play a more creative role in research in the future.

We carry smartphones in our pockets, the streets are dotted with semi-autonomous cars, but in the research laboratory experiments are still being designed by...

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Let the good tubes roll

19.01.2018 | Materials Sciences

How cancer metastasis happens: Researchers reveal a key mechanism

19.01.2018 | Health and Medicine

Meteoritic stardust unlocks timing of supernova dust formation

19.01.2018 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>