Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA

Macrophages Expressing a Modified Human Sodium Channel Protein Prevent or Reverse Multiple Sclerosis in a Mouse Model

By BiotechDaily International staff writers
Posted on 14 Jun 2013
Genetically engineered mouse macrophages expressing the human gene (SCN5A) that encodes the NaVI.5 (sodium channel, voltage-gated, type V, alpha subunit) sodium channel protein were used to demonstrate the potential use of these modified immune cells for the treatment of muscular sclerosis (MS).

NaVI.5 is an integral membrane protein and tetrodotoxin-resistant voltage-gated sodium channel subunit. This protein is found primarily in cardiac muscle and is responsible for the initial upstroke of the action potential in an electrocardiogram.

Investigators at the University of Wisconsin (Madison, USA) had shown previously that a splice variant of NaV1.5 was expressed intracellularly in human – but not mouse - macrophages, and that it regulated cellular signaling. The lack of this channel protein in mouse macrophages made it very difficult to study.

To counter this problem the investigators developed a novel transgenic mouse model (C57BL6c-fms-hSCN5A), in which the human macrophage NaV1.5 splice variant was expressed in vivo in mouse macrophages. They used these modified macrophages in studies carried out on mice with experimental autoimmune encephalomyelitis—a syndrome that closely mimics human muscular sclerosis.

Results published in the June 2013 issue of the Journal of Neuropathology and Experimental Neurology revealed that the mice expressing human NaV1.5 were protected from experimental autoimmune encephalomyelitis. The modified macrophages sought out the lesions caused by the disease and promoted recovery.

Mice with experimental autoimmune encephalomyelitis that lacked human NaV1.5 macrophages displayed symptoms of a chronic disease, which progressed from weakness of the back and front limbs to complete paralysis of the hind limbs. When macrophages expressing human NaV1.5 were transplanted into these mice, the animals regained the ability to walk. Mice treated with a placebo solution or normal mouse macrophages did not show any signs of recovery or became progressively more ill.

"This finding was unexpected because we were not sure how much damage they would do, versus how much cleaning up they would do,'' said senior author Dr. Michael Carrithers, assistant professor of neurology at the University of Wisconsin. "Some people thought the mice would get more ill, but we found that it protected them and they either had no disease or a very mild case."

The question remains as to why human NaV1.5 macrophages fail to protect humans from MS. "Why are these repair mechanisms deficient in patients with MS and what can we do to enhance them?'' asked Dr. Carrithers. "The long-range goal is to develop the NaV1.5 enhanced macrophages as a treatment for people with MS."


Related Links:

University of Wisconsin



Channels

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Program Designed to Provide High-Performance Computing Cluster Systems for Bioinformatics Research

Dedicated Computing (Waukesha, WI, USA), a global technology company, reported that it will be participating in the Intel Cluster Ready program to deliver integrated high-performance computing cluster solutions to the life sciences market. Powered by Intel Xeon processors, Dedicated Computing is providing a range of... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.