Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Promising therapy for ALS delivers antisense drug directly to nervous system

Researchers from the University of California, San Diego (UCSD) School of Medicine, the Center for Neurologic Study and Isis Pharmaceutical Corporation have designed and tested a molecular therapy in animals that they hope will be a major development in the fight to treat amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease.

The study conducted in the laboratory of Don Cleveland, Ph.D., UCSD Professor of Medicine, Neurosciences and Cellular and Molecular Medicine and member of the Ludwig Institute for Cancer Research, shows that therapeutic molecules known as antisense oligonucleotides can be delivered to the brain and spinal cord through the cerebrospinal fluid (CSF) at doses shown to slow the progression of ALS in rats. The study will be published July 27 in advance of publication in the August issue of Journal of Clinical Investigation.

With colleagues Timothy Miller, M.D., Ph.D., UCSD Department of Neurosciences, and Richard A. Smith, M.D., of the Center for Neurologic Study, Cleveland found that when effective doses of the antisense therapy were delivered, far less of a protein that causes a hereditable form of amyotrophic lateral sclerosis was produced.

ALS is a progressive disease that attacks motor neurons that reach from the brain to the spinal cord and from the spinal cord to the muscles throughout the body. Estimated to affect some 30,000 Americans, most people are diagnosed with ALS between the ages of 40 and 70. Typically, ALS patients live only three to five years after initial diagnosis.

Neurotoxicity from an accumulation of mutant proteins is believed to be at the root of many neurodegenerative diseases. ALS can be caused by a mutation in a protein called SOD1, and the antisense drug effectively silences the gene that codes for this mutant protein – found in the cells of patients with inherited forms of ALS.

In this disease, selective killing of spinal cord "motor neurons" occurs. Motor neurons are long and complex nerve cells that control voluntary movement. Degeneration of motor neurons in ALS leads to progressive loss of muscle control, paralysis and untimely death.

Healthy "neighbor" or supporting non-neuronal cells also have a protective effect on damaged mutant motor neurons, slowing the progression of ALS even when the nerve cells carry the mutant gene. The researchers speculate that the non-neuronal cells play a vital role in nourishing the motor neurons and in scavenging toxins from the cellular environment.

The onset and progression of disease in inherited ALS is determined by the motor neurons and microglia, small immune cells in the spinal cord, which migrate through nerve tissue and remove damaged cells and debris. Damage to motor neurons determines timing of disease onset. Microglia – the neighborhood, or "helper" cells – are then activated to help nourish the motor neurons and clean out debris like a vacuum cleaner. But because these neighboring cells are also damaged, they hurt instead of help, thus speeding disease progression.

When the UCSD researchers isolated and shut off mutant SOD1genes in the motor neuron cells only, the disease onset slowed, but the course of the disease eventually caught up to the control rodents. When mutant genes in only the microglia were silenced, the scientists found almost no effect on disease onset, however the disease progression was significantly slowed.

This discovery – authored by UCSD investigators Severine Boillee, Koji Yamanaka, Cleveland and others and published in the June 2 issue of the journal Science – confirms the importance of the new therapeutic approach, which delivers an antisense drug directly to the whole nervous system, including non-neuronal cells.

"Limiting mutant damage to microglia robustly slowed the disease's course, even when all motor neurons were expressing high levels of a SOD1 mutant," said Cleveland. "Our research suggests that what starts ALS and what keeps it going are two separate phases; it also suggests that with the right therapy, ALS could become a manageable, chronic disease."

Within a year, Cleveland hopes the first clinical trial will be initiated in humans. In order to deliver the antisense drug directly to the nervous system, surgeons will insert a small pump into a patient using a fairly routine surgery that has already been approved for management of pain. A small catheter is then implanted into the area surrounding the spinal cord, in order to pump antisense oligonucleotide drugs directly into the nervous system.

The investigators noted that if the antisense approach works for ALS – by delivering therapeutic agents for neurodegenerative diseases across the highly impermeable blood-brain barrier – it would likely also work in other neurodegenerative conditions, including Alzheimer's, Parkinson's and Huntington's diseases.

"We know we're on target with the pathogenic mechanism," said Cleveland. The remaining question is whether the genetic-based therapy will be tolerated. "If tolerated, this sets the stage for broader treatment of neurodegenerative disease, especially Huntington's disease, where there is currently no treatment, but key genes involved in promoting disease are known."

Debra Kain | EurekAlert!
Further information:

More articles from Health and Medicine:

nachricht Resolving the mystery of preeclampsia
21.10.2016 | Universitätsklinikum Magdeburg

nachricht New potential cancer treatment using microwaves to target deep tumors
12.10.2016 | University of Texas at Arlington

All articles from Health and Medicine >>>

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 >>>