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 Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute

nachricht Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>