NOV 14, 2016 1:02 PM PST

Alternative Treatments for MS Provide New Hope

WRITTEN BY: Kara Marker
Interferon drugs have long been used as treatments for multiple sclerosis (MS), an autoimmune disease where damaged nerves cause a range of neurological symptoms in those afflicted. But interferon drugs only help about 50 percent of MS patients. What’s the other half supposed to do?
A microscope view of neurons (green) and immune cells (red) inside the brain of a mouse with a drug-resistant form of a disease closely related to MS. Credit: Mari Shinohara
From Duke University in North Carolina, researchers are looking at an alternate option, for when interferon (INF) beta treatment doesn’t cut it. "The study shows a really clear molecular mechanism that may explain why some people do not respond to interferon-beta treatment," said senior author Mari Shinohara, PhD. "We've found what makes a difference in the response."

Every individual’s battle with MS differs, depending on, scientists believe, “the exact mix of genetic factors and environmental stimuli” that led to the onset of the disease in the first place.

In 2012, Shinohara led a study that explored how INF-beta works, and it’s by inhibiting a large immune complex: the NLRP3 inflammasome, which is vital for the onset of autoimmune reactions that cause MS symptoms, as immune cells mistakenly target the myelin sheath that coats and protects nerves. Without myelin, nerve signals don’t get the right message to the right place, leading to painful and debilitating neurological symptoms.

By studying an MS-related disease in mice, Shinohara and her team found that some mice experienced MS symptoms even if they lacked the NLRP2 inflammasome, so treatments targeting the inflammasome would be completely useless. Researchers believe that the same reason must explain cases of MS in humans that don’t respond to INF-beta drugs.

Now Shinohara and other researchers from Duke focused on the biological mechanisms associated with the seemingly alternative form of MS, the form that’s non-responsive to INF-beta drugs.

How is this form of MS that is unassociated with the NLRP3 inflammasome triggered? "We knew the second pathway bypassed the NLRP3 inflammasome," Shinohara said. "So the question became, what is actually involved?"

They found two receptors that seemed to be the culprits for the development of this form of MS: CXCR2 and LTBR. Indeed, inhibiting these receptors in the mice with non-NLRP3 inflammasome MS improved their condition.

Could this approach also work for humans? The Duke study used data from the MURDOCK MS study at the North Carolina Research Campus in Kannapolis, NC. By comparing genetic data from individuals with MS involved in the study based on whether they responded to INF-beta treatments or not, researchers could identify the biomarkers indicating what was triggering the difference in the two disease types.

"We identified individuals who were not responsive to the interferon-beta treatment, and looked at their CXCR2 and LTBR relative gene expression levels," said co-author Simon Gregory. "We found [the two gene receptors] to be upregulated.”

Gregory is leading a new research initiative, Discovery MS, that launched last week in Kannapolis. Discovery MS will continue to use MURDOCK MS study data and raise private funds to understand the origin of MS, works towards more effective treatments, accurate diagnoses, and better predictions of disease progression.

Shinohara and Gregory plan to continue pursuing CXCR2- and LTBR-related treatments for MS as well as screening processes to predict whether MS patients will benefit from INF-beta or CXCR2 and LTBR receptor treatments. “These patients have to go through all the pain, inconvenience and cost of interferon-beta treatment, only to be told that it doesn't work for them," Shinohara said. "So it's a big problem, and it would be really nice if we could tell upfront which treatment works."

The present study was published in the journal Nature Neuroscience.
 


Sources: Duke University, Discovery MS, North Carolina Research Campus
About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
AUG 17, 2020
Immunology
Nervous Protein Neuromedin B May Prevent Immune Reactivity
AUG 17, 2020
Nervous Protein Neuromedin B May Prevent Immune Reactivity
A protein produced by the nervous system seems to play a role in regulating the immune system. For people with inflammat ...
SEP 07, 2020
Immunology
CRISPR Pumps the Brakes on the Immune System to Support Gene Therapies
SEP 07, 2020
CRISPR Pumps the Brakes on the Immune System to Support Gene Therapies
The ability to edit the human genome using CRISPR has been heralded as a revolution in medicine. However, one of the big ...
SEP 16, 2020
Immunology
Depression, but Not Anxiety, Causes Inflammation and Metabolic Imbalances
SEP 16, 2020
Depression, but Not Anxiety, Causes Inflammation and Metabolic Imbalances
Scientists have discovered that depressed individuals show higher levels of inflammation as well as elevated fat concent ...
OCT 06, 2020
Drug Discovery & Development
New Immunotherapy Drug Effective Against Lung Cancer
OCT 06, 2020
New Immunotherapy Drug Effective Against Lung Cancer
A new study has confirmed that Tecentriq, an immunotherapy drug, improves survival rates among those with newly diagnose ...
OCT 14, 2020
Immunology
Self-Healing Microcapsules Make Promising Leukemia Vaccines
OCT 14, 2020
Self-Healing Microcapsules Make Promising Leukemia Vaccines
Leukemia is a cancer affecting tissues in the body that produce blood cells, including the bone marrow and the lymphatic ...
OCT 22, 2020
Cell & Molecular Biology
How a Gene Variant Raises the Risk of Multiple Sclerosis
OCT 22, 2020
How a Gene Variant Raises the Risk of Multiple Sclerosis
Now that sequencing the whole human genome is easier, faster, and cheaper than it used to be, scientists have been able ...
Loading Comments...