Corporate Banner
Satellite Banner
Proteomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Absence of Gene Leads to Earlier, More Severe Case of Multiple Sclerosis

Published: Tuesday, June 25, 2013
Last Updated: Tuesday, June 25, 2013
Bookmark and Share
UCSF finding in animal study may lead to biomarker that predicts course of disease in humans.

A UC San Francisco-led research team has identified the likely genetic mechanism that causes some patients with multiple sclerosis (MS) to progress more quickly than others to a debilitating stage of the disease. This finding could lead to the development of a test to help physicians tailor treatments for MS patients.

Researchers found that the absence of the gene Tob1 in CD4+ T cells, a type of immune cell, was the key to early onset of more serious disease in an animal model of MS.

Senior author Sergio Baranzini, PhD, a UCSF associate professor of neurology, said the potential development of a test for the gene could predict the course of MS in individual patients.

The study, done in collaboration with UCSF neurology researchers Scott Zamvil, MD, and Jorge Oksenberg, PhD, was published on June 24 in the Journal of Experimental Medicine.

MS is an inflammatory disease in which the protective myelin sheathing that coats nerve fibers in the brain and spinal cord is damaged and ultimately stripped away – a process known as demyelination. During the highly variable course of the disease, a wide range of cognitive, debilitating and painful neurological symptoms can result.

In previously published work, Baranzini and his research team found that patients at an early stage of MS, known as clinically isolated syndrome, who expressed low amounts of Tob1 were more likely to exhibit further signs of disease activity – a condition known as relapsing-remitting multiple sclerosis – earlier than those who expressed normal levels of the gene.

The current study, according to Baranzini, had two goals: to recapitulate in an animal model what the researchers had observed in humans, and uncover the potential mechanism by which it occurs.

The authors were successful on both counts. They found that when an MS-like disease was induced in mice genetically engineered to be deficient in Tob1, the mice had significantly earlier onset compared with wild-type mice, and developed a more aggressive form of the disease.

Subsequent experiments revealed the probable cause: the absence of Tob1 in just CD4+ T cells. The scientists demonstrated this by transferring T cells lacking the Tob1 gene into mice that had no immune systems but had normal Tob1 in all other cells. They found that the mice developed earlier and more severe disease than mice that had normal Tob1 expression in all cells including CD4+.

“This shows that Tob1 only needs to be absent in this one type of immune cell in order to reproduce our initial observations in mice lacking Tob1 in all of their cells,” said Baranzini.
Personalized Treatments for MS Patients

The researchers also found the likely mechanism of disease progression in the Tob1-deficient mice: higher levels of Th1 and Th17 cells, which cause an inflammatory response against myelin, and lower levels of Treg cells, which normally regulate inflammatory responses. The inflammation results in demyelination.

The research is significant for humans, said Baranzini, because the presence or absence of Tob1 in CD4+ cells could eventually serve as a prognostic biomarker that could help clinicians predict the course and severity of MS in individual patients. “This would be useful and important,” he said, “because physicians could decide to switch or modify therapies if they know whether the patient is likely to have an aggressive course of disease, or a more benign course.”

Ultimately, predicted Baranzini, “This may become an example of personalized medicine. When the patient comes to the clinic, we will be able to tailor the therapy based on what the tests tell us. We’re now laying the groundwork for this to happen.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Clearest Ever Images of Enzyme that Plays Key Roles in Aging, Cancer
UCLA-led research on telomerase could lead to new strategies for treating disease
Monday, October 19, 2015
Crop Cure
Scientists in new center to use medical research techniques to help food crops withstand drought and climate change.
Friday, October 16, 2015
Industry-Sponsored Academic Inventions Spur Increased Innovation
Analysis questions assumption that corporate support skews science toward inventions that are less useful than those funded by the government or non-profit organizations.
Monday, March 24, 2014
Structure of Key Pain-Related Protein Unveiled
In a technical tour de force, scientists have determined, at near-atomic resolution, the structure of a protein that plays a central role in the perception of pain and heat.
Friday, December 06, 2013
Chemical Signature for Fast Form of Parkinson's Found
The physical decline experienced by Parkinson's disease patients eventually leads to disability and a lower quality of life.
Monday, November 25, 2013
New Insights into How Proteins Regulate Genes
Researchers have developed a new way to parse and understand how special proteins called "master regulators" read the genome, and consequently turn genes on and off.
Monday, October 21, 2013
Cell Growth Discovery Has Implications for Targeting Cancer
The way cells divide to form new cells is controlled in previously unsuspected ways.
Monday, October 21, 2013
Discovery Could Lead to Saliva Test for Pancreatic Cancer
The disease is typically diagnosed through an invasive and complicated biopsy.
Tuesday, October 15, 2013
Tuberculosis and Parkinson’s Disease Linked by Unique Protein
UCSF researchers seek way to boost protein to fight both diseases.
Wednesday, September 11, 2013
Effects of Parkinson’s Disease Mutation Reversed in Cells
UCSF study used chemical commonly found in anti-wrinkle cream.
Friday, August 23, 2013
Dentistry School Receives $5M to Study Saliva Biomarkers
Imagine having a sample of your saliva taken at the dentist's office, and then learning within minutes whether your risk for stomach cancer is higher than normal.
Thursday, August 15, 2013
Scientists Devise Innovative Method to Profile and Predict the Behavior of Proteins
A class of proteins that are made up of multiple, interlocking molecular components, enzymes perform a variety of tasks inside each cell.
Friday, August 09, 2013
Immune System Molecule Promotes Tumor Resistance
A team of scientists has shown for the first time that a signaling protein involved in inflammation also promotes tumor resistance to anti-angiogenic therapy.
Tuesday, August 06, 2013
Failure to Destroy Toxic Protein Contributes to Progression of Huntington’s Disease
Gladstone-led study also finds target that boosts protein clearance, prolongs cell life.
Tuesday, July 23, 2013
Deadliest Cancers May Respond to New Drug Treatment Strategy
Researchers have found a way to knock down cancers caused by a tumor-driving protein called “myc,” paving the way for clinical trials.
Monday, July 22, 2013
Scientific News
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Natural Protein Points to New Inflammation Treatment
Findings may offer insight to effective treatments for inflammatory diseases, such as rheumatoid arthritis, psoriasis, and multiple sclerosis.
Enzyme Links Age-Related Inflammation, Cancer
Researchers have shown that an enzyme key to regulating gene expression -- and also an oncogene when mutated -- is critical for the expression of numerous inflammatory compounds that have been implicated in age-related increases in cancer and tissue degeneration.
New Biomarker to Assess Stem Cells Developed
A research team led by scientists from UCL have found a way to assess the viability of 'manufactured' stem cells known as induced pluripotent stem cells (iPSCs). The team's discovery offers a new way to fast-track screening methods used in stem cell research.
Therapy Halts Progression of Lou Gehrig’s Disease
Researchers at Oregon State University announced today that they have essentially stopped the progression of amyotrophic lateral sclerosis (ALS), or Lou Gehrig’s disease, for nearly two years in one type of mouse model used to study the disease – allowing the mice to approach their normal lifespan.
Crouching Protein, Hidden Enzyme
A new study led by scientists at The Scripps Research Institute (TSRI) and the University of California (UC), Berkeley shows how a crucial molecular enzyme starts in a tucked-in somersault position and flips out when it encounters the right target.
HIV Protein Manipulates Hundreds of Human Genes
Findings search for new or improved treatments for patients with AIDS.
First 3-D Vision of Cancer Target
This basic research set the grounds for structure-based drug design approaches that could be beneficial for cancer treatments' - Dr. Cyril Dominguez, University of Leicester.
New Light Shed on Genetic Regulation
A team of scientists has uncovered greater intricacy in protein signaling than was previously understood, shedding new light on the nature of genetic production.
Hacking the Programs of Cancer Stem Cells
All tumor cells are the offspring of a single, aberrant cell, but they are not all alike.
Scroll Up
Scroll Down
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!