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news.Researchers 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.
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The researchers were from the University of California, San Diego (UCSD) School of Medicine, the Center for Neurologic Study and Isis Pharmaceutical. Their study 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 amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig’s disease) in rats.
They found that, when effective doses of the antisense therapy were delivered, far less of a protein that causes a hereditable form of ALS was produced.
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.
The discovery confirms the importance of the new therapeutic approach, which delivers an antisense drug directly to the whole nervous system, including non-neuronal cells.
Within a year, the scientists hope that the first clinical trial will be initiated in humans.
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 also be likely to 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 Dr Don Cleveland, UCSD professor of medicine, neurosciences and cellular and molecular medicine and member of the Ludwig Institute for Cancer Research. “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.”