Related Experiment Video
Updated: May 5, 2026
14:55
Direct Intraventricular Delivery of Drugs to the Rodent Central Nervous System
Published on: May 12, 2013
61.3K
Antisense oligonucleotide therapy for neurodegenerative disease
Richard A Smith1, Timothy M Miller, Koji Yamanaka
1Ludwig Institute for Cancer Research, University of California, San Diego, La Jolla, California, USA.
The Journal of Clinical Investigation
|August 1, 2006
Summary
Researchers developed a new antisense oligonucleotide therapy to reduce toxic protein buildup in neurodegenerative diseases. This treatment effectively lowered superoxide dismutase 1 (SOD1) levels and slowed disease progression in a model of amyotrophic lateral sclerosis (ALS).
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Protein misfolding and accumulation drive neurodegenerative disease pathogenesis.
- Targeting gene expression offers a therapeutic strategy for these conditions.
- Antisense oligonucleotides (ASOs) can be modified for CNS delivery.
Purpose of the Study:
- To evaluate the efficacy of intraventricularly infused ASOs for downregulating gene expression in the CNS.
- To investigate the therapeutic potential of ASOs targeting superoxide dismutase 1 (SOD1) in a model of amyotrophic lateral sclerosis (ALS).
Main Methods:
- Modified ASOs were infused intraventricularly in rodents and primates.
- ASOs targeting SOD1 were administered to a mouse model of ALS.
- SOD1 protein and mRNA levels were quantified throughout the CNS.
- Disease progression was monitored in the ALS model.
Main Results:
- Intraventricular ASO infusion led to widespread CNS distribution.
- SOD1 ASOs significantly reduced SOD1 protein and mRNA levels in the brain and spinal cord.
- Early treatment with SOD1 ASOs substantially slowed disease progression in the ALS model.
Conclusions:
- Direct CNS delivery of ASOs is a viable strategy for treating neurodegenerative diseases.
- ASO therapy can effectively downregulate target proteins like SOD1.
- This approach holds promise for treating ALS and other neurodegenerative disorders with known targets.
More Related Videos
Related Concept Videos
01:23RNA Interference
24.4K
RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
24.4K
02:30siRNA - Small Interfering RNAs
13.4K
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
13.4K
02:15Experimental RNAi
6.5K
RNA interference (RNAi) is a cellular mechanism that inhibits gene expression by suppressing its transcription or activating the RNA degradation process. The mechanism was discovered by Andrew Fire and Craig Mello in 1998 in plants. Today, it is observed in almost all eukaryotes, including protozoa, flies, nematodes, insects, parasites, and mammals. This precise cellular mechanism of gene silencing has been developed into a technique that provides an efficient way to identify and determine the...
6.5K
01:22Alzheimer's Disease: Treatment
1.3K
Alzheimer's Disease (AD), a neurodegenerative disorder, is pathologically identified by amyloid plaques and neurofibrillary tangles composed of tau protein. AD pharmacotherapy aims to manage cognitive symptoms, delay disease progression, and treat behavioral symptoms. The treatment is primarily symptomatic and palliative, with no definitive disease-modifying therapy available. Cholinesterase inhibitors, including donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne), are...
1.3K
01:29Alzheimer Disease l: Introduction
29
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
29
01:23Alzheimer Disease ll: Pathophysiology
42
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and...
42