Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Rare, lethal childhood disease tracked to protein

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:

More articles from Life Sciences:

nachricht Novel mechanisms of action discovered for the skin cancer medication Imiquimod
21.10.2016 | Technische Universität München

nachricht Second research flight into zero gravity
21.10.2016 | Universität Zürich

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: New 3-D wiring technique brings scalable quantum computers closer to reality

Researchers from the Institute for Quantum Computing (IQC) at the University of Waterloo led the development of a new extensible wiring technique capable of controlling superconducting quantum bits, representing a significant step towards to the realization of a scalable quantum computer.

"The quantum socket is a wiring method that uses three-dimensional wires based on spring-loaded pins to address individual qubits," said Jeremy Béjanin, a PhD...

Im Focus: Scientists develop a semiconductor nanocomposite material that moves in response to light

In a paper in Scientific Reports, a research team at Worcester Polytechnic Institute describes a novel light-activated phenomenon that could become the basis for applications as diverse as microscopic robotic grippers and more efficient solar cells.

A research team at Worcester Polytechnic Institute (WPI) has developed a revolutionary, light-activated semiconductor nanocomposite material that can be used...

Im Focus: Diamonds aren't forever: Sandia, Harvard team create first quantum computer bridge

By forcefully embedding two silicon atoms in a diamond matrix, Sandia researchers have demonstrated for the first time on a single chip all the components needed to create a quantum bridge to link quantum computers together.

"People have already built small quantum computers," says Sandia researcher Ryan Camacho. "Maybe the first useful one won't be a single giant quantum computer...

Im Focus: New Products - Highlights of COMPAMED 2016

COMPAMED has become the leading international marketplace for suppliers of medical manufacturing. The trade fair, which takes place every November and is co-located to MEDICA in Dusseldorf, has been steadily growing over the past years and shows that medical technology remains a rapidly growing market.

In 2016, the joint pavilion by the IVAM Microtechnology Network, the Product Market “High-tech for Medical Devices”, will be located in Hall 8a again and will...

Im Focus: Ultra-thin ferroelectric material for next-generation electronics

'Ferroelectric' materials can switch between different states of electrical polarization in response to an external electric field. This flexibility means they show promise for many applications, for example in electronic devices and computer memory. Current ferroelectric materials are highly valued for their thermal and chemical stability and rapid electro-mechanical responses, but creating a material that is scalable down to the tiny sizes needed for technologies like silicon-based semiconductors (Si-based CMOS) has proven challenging.

Now, Hiroshi Funakubo and co-workers at the Tokyo Institute of Technology, in collaboration with researchers across Japan, have conducted experiments to...

All Focus news of the innovation-report >>>



Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

Agricultural Trade Developments and Potentials in Central Asia and the South Caucasus

14.10.2016 | Event News

World Health Summit – Day Three: A Call to Action

12.10.2016 | Event News

Latest News

Resolving the mystery of preeclampsia

21.10.2016 | Health and Medicine

Stanford researchers create new special-purpose computer that may someday save us billions

21.10.2016 | Information Technology

From ancient fossils to future cars

21.10.2016 | Materials Sciences

More VideoLinks >>>