Satellite Banner
Genomics
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 4,000+ scientific posters on ePosters
  • More than 5,300+ 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

Genetics Control Regenerative Properties Of Stem Cells
Researchers define how genetic factors control regenerative properties of blood-forming stem cells.
Thursday, December 08, 2016
Zika Virus Infection Alters Human and Viral RNA
Researchers have discovered that Zika infections results in human and viral genetic modification.
Monday, October 24, 2016
Transcription Factor Isoforms Implicated in Colon Diseases
UC Riverside study explains how distribution of two forms of a transcription factor in the colon influence risk of disease.
Thursday, May 19, 2016
Fructose Alters Hundreds of Brain Genes
UCLA scientists report that diet rich in omega-3 fatty acids can reverse the damage.
Tuesday, April 26, 2016
Study Yields the Key to Effective Personalized Medicine
A team of UCLA bioengineers and surgeons has taken a major step toward making personalized medicine a reality.
Monday, April 11, 2016
Crowdfunding the Fight Against Cancer
From budding social causes to groundbreaking businesses to the next big band, crowdfunding has helped connect countless worthy projects with like-minded people willing to support their efforts, even in small ways. But could crowdfunding help fight cancer?
Monday, February 08, 2016
Science Magazine Names CRISPR ‘Breakthrough of the Year’
In its year-end issue, the journal Science chose the CRISPR genome-editing technology invented at UC Berkeley 2015’s Breakthrough of the Year.
Monday, December 21, 2015
CRISPR-Cas9 Helps Uncover Genetics of Exotic Organisms
A new study illustrates the ease with which CRISPR-Cas9 can knock out genes in exotic animals to learn how those genes control growth and development.
Friday, December 11, 2015
New Method for Screening Cancer Cells
Parallel microfiltration could lead to better treatments for a number of diseases, UCLA-led study says.
Thursday, December 03, 2015
RNA-Based Drugs Give More Control Over Gene Editing
CRISPR/Cas9 gene editing technique can be transiently activated and inactivated using RNA-based drugs, giving researchers more precise control in correcting and inactivating genes.
Monday, November 23, 2015
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
Rare Childhood Leukemia Reveals Surprising Genetic Secrets
A coalition of leukemia researchers led by scientists from UC San Francisco has discovered surprising genetic diversity in juvenile myelomonocytic leukemia (JMML), a rare but aggressive childhood blood cancer.
Thursday, October 15, 2015
Double Enzyme Hit May Explain Common Cancer Drug Side Effect
Mouse study suggests genomic screening before treatment may help prevent anemia.
Wednesday, October 14, 2015
New Autism Genes Are Revealed in Largest-Ever Study
Work draws more detailed picture of genetic risk, sheds light on sex differences in diagnosis.
Wednesday, September 30, 2015
Scientific News
Big Genetics in BC: The American Society for Human Genetics 2016 Meeting
Themes at this year's meeting ranged from the verification, validation, and sharing of data, to the translation of laboratory findings into actionable clinical results.
Personality Traits, Psychiatric Disorders Linked to Specific Genomic Locations
Researchers have unearthed genetic correlations between personality traits and psychiatric disorders.
Genetics Control Regenerative Properties Of Stem Cells
Researchers define how genetic factors control regenerative properties of blood-forming stem cells.
Diabetes Missing Link Discovered
Researchers from the University of Auckland have shown that beta catenin plays a vital role in the control of insulin release from the pancreas.
Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal, but dysregulation contributes to cancer development.
Gene-Editing Improves Vision in Blind Rats
Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.
Gene Editing Yields Tomatoes That Ripen Weeks Earlier
Research team develop method to make tomato plants flower and ripen fruit two weeks faster than current growth rates.
Exploring the Genome of the River Blindness Parasite
Researchers have decoded the genome of the parasite that causes the skin and eye infection known as river blindness.
Gene Therapy Maintains Clotting Factor for Hemophilia Patients
Following a single gene therapy dose, the highest levels of an essential blood clotting factor IX were observed in hemophilia B patients.
Unexpected Role for Epigenetic Enzymes in Cancer
Researchers use epigenetics to identify the role of an enzyme family as regulators of genetic message interpretation in yeast.
Skyscraper Banner

SELECTBIO Market Reports
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
4,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!