Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Rare, lethal childhood disease tracked to protein

30.04.2013
A team of international researchers led by Northwestern Medicine scientists has identified how a defective protein plays a central role in a rare, lethal childhood disease known as Giant Axonal Neuropathy, or GAN. The finding is reported in the May 2013 Journal of Clinical Investigation.

GAN is an extremely rare and untreatable genetic disorder that strikes the central and peripheral nervous systems of young children. Those affected show no symptoms at birth; typically around age three the first signs of muscle weakness appear and progress slowly but steadily. Children with GAN experience increasing difficulty walking and are often wheelchair-bound by age 10. Over time, they become dependent on feeding and breathing tubes. Only a few will survive into young adulthood.

In GAN patients, nerve cells are swollen with massive build-ups of structures called intermediate filaments, cytoskeletal components that give cells their shape and mechanical properties. Goldman's team found that gigaxonin, a protein encoded by the gene involved in GAN, regulates normal turnover of the protein building blocks that form a cell's intermediate filaments. Mutations in this gene result in the malfunctioning of gigaxonin, which leads to the abnormal build-up of intermediate filaments and eventually disrupts the normal functioning of nerve cells.

"This important new research pinpoints the mechanism that allows intermediate filaments to rapidly build up in GAN patients," says Robert Goldman, chair of the department of cell and molecular biology at Northwestern University Feinberg School of Medicine. Goldman has studied the structural proteins of cells for more than 30 years.

"This is a huge step forward for GAN research," said Lori Sames, co-founder and CEO of Hannah's Hope Fund, the leading GAN disease organization. "GAN is juvenile ALS, but even worse. Not only do motor neurons die out, so do the sensory neurons. To find a medicinal therapy, you really need to know what mechanism to target. And thanks to Dr. Goldman's work, now we do."

To identify gigaxonin's role, scientists used cells known as fibroblasts obtained from skin biopsies of children with GAN. The cells were then grown in lab cultures, and they also contained large abnormal aggregates of intermediate filaments. When scientists introduced healthy gigaxonin genes into both control and patient fibroblasts, the results were dramatic. The abnormal aggregates of intermediate filaments disappeared. However, the cytoskeleton's two other major systems, microtubules and actin filaments were not affected by this treatment.

The study's lead author, Northwestern University postdoctoral fellow Saleemulla Mahammad, stressed that this discovery may also have implications for more common types of neurodegenerative diseases that are also characterized by large accumulations of intermediate filament proteins, including Alzheimer's disease and Parkinson's disease.

"Our results suggest new pathways for disease intervention," he said. "Finding a chemical component that can clear the intermediate filament aggregations and restore the normal distribution of intermediate filaments in cells could one day lead to a therapeutic agent for many neurological disorders."

Mahammad and other members of the Goldman Laboratory collaborated with Puneet Opal, M.D., associate professor in the Ken and Ruth Davee department of neurology and cell and molecular biology, along with researchers in the laboratory of Pascale Bomont, at the INSERM neurological institute in Montpelier, France, and the laboratory of Jean-Pierre Julien at the Université Laval in Quebec, Canada.

This research was supported by the National Institute of General Medical Sciences NIH grant 1P01GM096971-01 and Hannah's Hope Fund. The leading GAN disease foundation, Hannah's Hope Fund, was established in 2008, and currently knows of 38 cases of the disease worldwide. The foundation is currently working towards funding a clinical trial for GAN gene therapy.

Marla Paul | EurekAlert!
Further information:
http://www.northwestern.edu

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>