|
ALS in the News
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."
General Health : Drug News - Food Consumer A review by the Food and Drug Administration shows that use of cholesterol-lowering drugs called statins does not increase incidence of amyotrophic lateral sclerosis (ALS) or commonly known as Lou Gehrig's Disease. Because of this, the FDA said on ...
FDA Finds No Link Between Statin Use and ALS - Medscape News October 2, 2008 (Silver Springs, MD) — A new Food and Drug Administration analysis has shown that statins do not increase the risk of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease [1]. The meta-analysis, which included 41 ...
New Journal to Explore Neurodegenerative, Neuroprotective and ... - Forbes WESTON, Mass., Oct. 2 /PRNewswire/ -- Weston Medical Publishing today announced publication of the first issue of Journal of Neurodegeneration and Regeneration. (ISSN 1932-1481) This new peer-reviewed journal is designed to explore all aspects of ...
ALS diagnosis leads man to author novel - Clay County Daily Advocate-Press Amyotrophic Lateral Sclerosis (ALS), commonly known as Lou Gehrig’s Disease, is a trying and ultimately fatal affliction. Normally, a patient has a three to five year life expectancy from the time of their diagnosis. While it would be a stretch ...
Walk seeks to keep hope alive for ALS victim from Scituate - Patriot Ledger When doctors told Judy Mullin she had Lou Gehrig’s disease, they didn’t sugarcoat the diagnosis. “They told us, very matter-of-fact, that this is what Judy had and the life expectancy was two to five years,” said her husband, Ed Mullin of ...
FDA Study: Statins Don’t Pose Risk Of Lou Gehrig’s Disease - Eflux Media Cholesterol-lowering drugs or statins do not increase the incidence of amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’ disease, according to an analysis made by the Food and Drug Administration, which was published on the Sept 29 ...
Aeolus Pharmaceuticals Announces Initiation Of Multiple Dose Study Of ... - Medical News Today Aeolus Pharmaceuticals, Inc. (OTCBB: AOLS) announced today that it has initiated a follow-on Phase I open label compassionate use multiple dose study of AEOL 10150 in a patient diagnosed with progressive and debilitating amyotrophic lateral sclerosis ...
Vets' Corner: VA establishes ALS as compensable illness - Saratogian Veterans with amyotrophic lateral sclerosis (ALS) may receive badly needed support for themselves and their families after the Department of Veterans Affairs (VA) announced that ALS will become a presumptively compensable illness for all veterans ...
Aeolus initiates Phase I amyotrophic lateral sclerosis study - Pharmaceutical Business Review The study is being conducted at University of California, Los Angeles by Martina Wiedau-Pazos and is designed to evaluate the safety and efficacy of AEOL 10150 in an ALS patient over an extended period of time. The patient will receive a subcutaneous ...
Man faces ALS with hope -and his eyes open - Owen Sound Sun Times It started as something insignificant -- an inability to use his left hand to properly grasp a coffee cup, to fasten the buttons on a shirt. Larry Vokes wasn't prepared for it to be a death sentence. And he's still not. While the Chatsworth man has ...
|
|