New vitamin-based treatment that could reduce muscle degeneration in muscular dystrophy

October 23, 2012

Boosting the activity of a vitamin-sensitive cell adhesion pathway has the potential to counteract the muscle degeneration and reduced mobility caused by muscular dystrophies, according to a research team led by scientists at the University of Maine.

The discovery, published 23 October in the open access journal , is particularly important for congenital muscular dystrophies, which are progressive, debilitating and often lethal diseases that currently remain without cure. The researchers found that they could improve and function in a zebrafish version of muscular dystrophy by supplying a common cellular chemical (or its precursor, vitamin B3) to activate a cell adhesion pathway.

Muscle cells are in themselves relatively delicate, but derive important additional from adhesion protein complexes; these anchor the muscle cells to an external framework known as the basement membrane, thereby helping to buffer the cells against the extreme forces that they experience during muscle contractions. Mutations in the genes that encode these adhesion proteins can weaken these attachments, making more susceptible to damage and death.

The resulting muscle degeneration can eventually lead to progressive muscle-wasting diseases, such as muscular dystrophies. A major component of the basement membrane, a protein called laminin, binds to multiple different receptors on the muscle cell surface and forms a dense, organized network.

The study was led by UMaine Associate Professor of Biological Sciences, Clarissa Henry, whose laboratory focuses on understanding how cell adhesion complexes contribute to . The researchers discovered that a pathway involving a common cellular chemical called nicotinamide adenine dinucleotide (NAD+) plays a role in the formation of organized basement membranes in muscle tissue, during development of the fish embryo. As disordered basement membranes are seen in many different types of muscular dystrophies, the researchers wondered whether activating this pathway might reduce the severity of some muscular dystrophies.

In the current study, the researchers show that NAD+ improves the organization of laminin in a zebrafish version of muscular dystrophy. Zebrafish lacking either of the two main receptors for laminin have a disorganized basement membrane, causing and difficulties with movement. However adding extra NAD+, or even a vitamin packet containing vitamin B3 (niacin, a precursor to NAD+), significantly reduced these symptoms.

The research team found that the main protective effects of NAD+ come from enhancing the organization of the laminin structure in the , which helps to increase the resilience of diseased muscle fibers.

Because the same cell adhesion complexes are found in humans, the research team is optimistic that these findings may one day positively impact patients with muscular dystrophies. "Although there is a long way to go, I'm hopeful that our data could eventually lead to new adjuvant therapies," says University of Maine Ph.D. student Michelle Goody, who led the research team with Prof. Henry.

Prof. Henry summarizes; "One of my favorite aspects of this study is that it is a poster child for how asking basic biological questions can lead to exciting discoveries that may have future therapeutic potential."

Explore further: Researchers review muscular dystrophy therapies

More information: PLoS Biol 10(10): e1001409. doi:10.1371/journal.pbio.1001409

Related Stories

Researchers review muscular dystrophy therapies

June 22, 2012
Leading muscular dystrophy researcher Dean Burkin, of the University of Nevada School of Medicine summarizes the impact of a new protein therapeutic, MG53, for the treatment of Duchenne muscular dystrophy in an article published ...

Stem cell foundation for muscular dystrophy treatment

July 14, 2011
Research at the Australian Regenerative Medicine Institute (ARMI) at Monash University could lay the groundwork for new muscular dystrophy treatments.

Study reveals enzyme function, could help find muscular dystrophy therapies

January 9, 2012
Researchers at the University of Iowa have worked out the exact function of an enzyme that is critical for normal muscle structure and is involved in several muscular dystrophies. The findings, which were published Jan. 6 ...

Successful transplant of patient-derived stem cells into mice with muscular dystrophy

June 27, 2012
Stem cells from patients with a rare form of muscular dystrophy have been successfully transplanted into mice affected by the same form of dystrophy, according to a new study published today in Science Translational Medicine.

Recommended for you

'Human chronobiome' study informs timing of drug delivery, precision medicine approaches

December 13, 2017
Symptoms and efficacy of medications—and indeed, many aspects of the human body itself—vary by time of day. Physicians tell patients to take their statins at bedtime because the related liver enzymes are more active during ...

Estrogen discovery could shed new light on fertility problems

December 12, 2017
Estrogen produced in the brain is necessary for ovulation in monkeys, according to researchers at the University of Wisconsin-Madison who have upended the traditional understanding of the hormonal cascade that leads to release ...

Time of day affects severity of autoimmune disease

December 12, 2017
Insights into how the body clock and time of day influence immune responses are revealed today in a study published in leading international journal Nature Communications. Understanding the effect of the interplay between ...

3-D printed microfibers could provide structure for artificially grown body parts

December 12, 2017
Much as a frame provides structural support for a house and the chassis provides strength and shape for a car, a team of Penn State engineers believe they have a way to create the structural framework for growing living tissue ...

Team identifies DNA element that may cause rare movement disorder

December 11, 2017
A team of Massachusetts General Hospital (MGH) researchers has identified a specific genetic change that may be the cause of a rare but severe neurological disorder called X-linked dystonia parkinsonism (XDP). Occurring only ...

Protein Daple coordinates single-cell and organ-wide directionality in the inner ear

December 11, 2017
Humans inherited the capacity to hear sounds thanks to structures that evolved millions of years ago. Sensory "hair cells" in the inner ear have the amazing ability to convert sound waves into electrical signals and transmit ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.