Amyotrophic Lateral Sclerosis (ALS)
Amyotrophic lateral sclerosis (ALS) is a rare neurological disease that affects nerve cells in the brain and spinal cord. With our company's profound expertise in ALS research, we are well-equipped to offer tailored solutions and comprehensive support to facilitate your research process from ALS therapy development to therapy commercialization.
Introduction to ALS
Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is a rare condition characterized by combined damage to upper and lower motor neurons. The incidence rate of ALS is 1.9/100,000. The typical symptoms of ALS include progressive muscle weakness, muscle atrophy, and muscle fasciculation. The majority of ALS individuals usually succumb to respiratory muscle paralysis and respiratory failure within 3 to 5 years after the onset of the disease.
Fig. 1 ALS phenotypic variation and spectrum with FTD. (Feldman, Eva L., et al., 2022)Pathogenesis of ALS
ALS predominantly affects motor neurons, which are responsible for regulating voluntary muscle movements. The degeneration and death of these motor neurons lead to the progressive loss of muscle control observed in ALS individuals. The pathogenesis of ALS is complex and multifactorial. While the precise etiology of ALS remains elusive, scientific investigations indicate that a combination of genetic and environmental factors contributes to its development.
Genetic Factors
Several genetic mutations have been identified in approximately 10% of ALS cases. These mutations affect genes such as SOD1, C9orf72, and TARDBP, among others. These genetic abnormalities contribute to the disruption of cellular processes, protein misfolding, and impaired RNA metabolism, ultimately leading to motor neuron degeneration.
Environmental Factors
Environmental factors such as exposure to toxins, smoking, and certain occupational hazards have been linked to a heightened risk of ALS development. These environmental factors are believed to interact with genetic susceptibility, potentially triggering the onset and progression of the disease.
Diagnostics of ALS
- Medical Examination
A medical examination is the basis for diagnosing ALS. Physicians will conduct regular neurological examinations and evaluate the complete medical history to analyze whether symptoms have worsened over time. Furthermore, diagnostic tests such as electromyography (EMG) and magnetic resonance imaging (MRI) can help exclude other conditions that present similar symptoms to ALS. - Biomarker Detection
Biomarkers, such as neurofilament light chain and phosphorylated neurofilament heavy chain, can be measured in cerebrospinal fluid or blood samples. These biomarkers provide valuable insights into the disease progression and response to therapeutics, facilitating early diagnosis and monitoring of ALS individuals.
Therapeutics Development of ALS
- Targets of ALS Therapy Development
| Target Name | Description |
|---|---|
| Glutamate Regulatory Pathway | Excessive glutamate, a neurotransmitter, has been implicated in the neuronal damage observed in ALS. Riluzole was the first drug approved by the FDA for the therapeutics of ALS. Its function is to reduce the release of glutamate and eliminate glutamate excitotoxicity. |
| Oxidative Stress Pathway | Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the antioxidant defense mechanisms, plays a crucial role in ALS pathogenesis. Edaravone is another FDA-approved drug for ALS therapeutics. It is an antioxidant that helps reduce oxidative stress. |
| Protein Misfolding and Aggregation | Abnormal protein aggregation is a hallmark of ALS, with aggregates of misfolded proteins, such as TDP-43 and SOD1, found in affected neurons. Radicicol is an investigational drug that targets heat shock protein 90 (Hsp90) and aims to promote protein folding and stability. |
- Types of ALS Therapy Development
- Gene Therapy Development
Gene therapies aim to correct or mitigate the effects of the mutated genes. Approaches include gene replacement therapy, gene editing (such as CRISPR-Cas9), or antisense oligonucleotides (ASOs) that can reduce the production of disease-causing proteins.
- Disease-Modifying Therapy Development
Disease-modifying therapies often focus on reducing neurotoxicity, oxidative stress, inflammation, or protein misfolding/aggregation. Examples include drugs that modulate glutamate excitotoxicity, enhance antioxidant defenses, regulate inflammation, or promote protein homeostasis.
Our Services
With years of extensive involvement in rare disease research, our company boasts a highly skilled team and vast expertise. We harness state-of-the-art technology to drive the development of innovative diagnostic tools, enabling early detection of ALS. By establishing animal models and conducting in-depth investigations into ALS pathogenesis and targets, we advance therapeutic drug development.
Our Research Platforms
Our Services
Animal Models of ALS
- Mutant SOD1 mouse models
- TDP-43 transgenic mouse models
- Mutant TDP-43 rat models
- Rodent models expressing mutant VCP
No matter what stage of research you are at, we can provide you with corresponding research services. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Feldman, Eva L., et al. "Amyotrophic lateral sclerosis." The Lancet 400.10360 (2022): 1363-1380.
- Goutman, Stephen A., et al. "Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis." The Lancet Neurology 21.5 (2022): 480-493.
- Philips, Thomas, and Jeffrey D. Rothstein. "Rodent models of amyotrophic lateral sclerosis." Current protocols in pharmacology 69.1 (2015): 5-67.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.