Corporate Banner
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
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 2,500+ scientific posters on ePosters
  • More than 3,700+ 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

Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Tuesday, July 28, 2015
Engineers Crack DNA Code of Autoimmune Disorders
Researchers have identified an unexpectedly general set of rules that determine which molecules can cause the immune system to become vulnerable to the autoimmune disorders lupus and psoriasis.
Wednesday, June 10, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 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
Researchers Change Cell Types by Flipping a Single Switch
New findings have identified a method for changing one cell type into another in a process called forced transdifferentiation.
Friday, December 06, 2013
Scientists Pinpoint Cell Type and Brain Region Affected by Gene Mutations in Autism
UCSF-led study zeroes in on when and where disrupted genes exert effects.
Tuesday, November 26, 2013
Digging Deeper Into Cancer
What a pathologist looks for in a Pap test sample, but hopes not to find, are oddly shaped cells with abnormally large nuclei. The same is true for prostate and lung cancer biopsies.
Tuesday, November 19, 2013
Nanotech Method Show Promise Against Pancreatic Cancer
Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed a new technique for fighting deadly and hard-to-treat pancreatic cancer.
Monday, November 18, 2013
Researchers Un-Junking Junk DNA
A study shines a new light on molecular tools our cells use to govern regulated gene expression.
Wednesday, November 13, 2013
Fast-Mutating DNA Sequences Shape Early Development
What does it mean to be human? According to scientists the key lies, ultimately, in the billions of lines of genetic code that comprise the human genome.
Wednesday, November 13, 2013
Did Inefficient Cellular Machinery Evolve to Fight Viruses and Jumping Genes?
UCSF scientist poses new theory on origins of eukaryotic gene expression.
Monday, November 11, 2013
Powerful Anti-Cancer Compound Safely Delivered
Researchers have discovered a way to effectively deliver staurosporine (STS).
Tuesday, October 22, 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
Single Gene Mutation Linked to Neurological Disorders
Mutation could offer insights into Alzheimer’s, Parkinson’s and Huntigton’s Diseases.
Wednesday, October 16, 2013
Scientific News
Poor Survival Rates in Leukemia Linked to Persistent Genetic Mutations
For patients with an often-deadly form of leukemia, new research suggests that lingering cancer-related mutations – detected after initial treatment with chemotherapy – are associated with an increased risk of relapse and poor survival.
Searching Big Data Faster
Theoretical analysis could expand applications of accelerated searching in biology, other fields.
Growing Hepatitis C in the Lab
Recent discovery allows study of naturally occurring forms of hepatitis C virus (HCV) in the lab.
Inciting an Immune Attack on Cancer Cells
A new minimally invasive vaccine that combines cancer cells and immune-enhancing factors could be used clinically to launch a destructive attack on tumors.
Reprogramming Cancer Cells
Researchers on Mayo Clinic’s Florida campus have discovered a way to potentially reprogram cancer cells back to normalcy.
Genetic Overlapping in Multiple Autoimmune Diseases May Suggest Common Therapies
CHOP genomics expert leads analysis of genetic architecture, with eye on repurposing existing drugs.
Surprising Mechanism Behind Antibiotic-Resistant Bacteria Uncovered
Now, scientists at TSRI have discovered that the important human pathogen Staphylococcus aureus, develops resistance to this drug by “switching on” a previously uncharacterized set of genes.
How DNA ‘Proofreader’ Proteins Pick and Edit Their Reading Material
Researchers from North Carolina State University and the University of North Carolina at Chapel Hill have discovered how two important proofreader proteins know where to look for errors during DNA replication and how they work together to signal the body’s repair mechanism.
Fat in the Family?
Study could lead to therapeutics that boost metabolism.
Tissue Bank Pays Dividends for Brain Cancer Research
Checking what’s in the bank – the Brisbane Breast Bank, that is – has paid dividends for UQ cancer researchers.
Skyscraper Banner

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
2,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!