Lambert-Eaton Myasthenic Syndrome (LEMS)
Lambert-Eaton myasthenic syndrome (LEMS) is an uncommon autoimmune condition affecting the neuromuscular junction. With our pioneering efforts in LEMS research, we are at the forefront of developing cutting-edge diagnostic tools and therapeutics to facilitate the effective management of LEMS. As your reliable partner in LEMS research, we offer unmatched support to fulfill your scientific research needs.
Introduction to LEMS
LEMS is a rare autoimmune disease that affects the neuromuscular junction, causing muscle weakness in the limbs. Approximately 60% of LEMS cases are often associated with an underlying malignancy (most commonly small cell lung cancer), making it a paraneoplastic syndrome. LEMS has an exceptionally low incidence rate, with a global prevalence estimated at approximately 2.8 cases per million individuals.
Fig. 1 Pathophysiology of LEMS and effects of symptomatic therapeutics. (Titulaer, Maarten J., et al., 2011)Pathogenesis of LEMS
The pathogenesis of LEMS revolves around the presence of autoantibodies targeting the presynaptic voltage-gated calcium channels (VGCCs), primarily the P/Q-type VGCCs. These autoantibodies disrupt the calcium influx at the nerve endings, leading to reduced acetylcholine release and subsequent muscle weakness. Additionally, other nerve terminal proteins may also be targeted, contributing to the overall impairment of neuromuscular transmission. Here are the potential mechanisms involved in LEMS.
Malignant Tumor
The malignant tumor cells express proteins similar to the presynaptic VGCCs, leading to an immune response targeting both the tumor and the neuromuscular junction.
Genetic Predisposition
Certain human leukocyte antigen (HLA) alleles have been associated with an increased susceptibility to the development of LEMS.
Immune Dysregulation
Infections or exposure to certain toxins may contribute to the development of LEMS by leading to the production of autoantibodies and activation of immune cells.
Diagnostics Development of LEMS
Achieving an accurate and prompt diagnosis of LEMS is vital to ensure effective management. Diagnostic approaches for LEMS encompass nerve conduction studies (NCS) and electromyography (EMG).
- Nerve Conduction Studies (NCS)
NCS entails the application of mild electrical pulses to nerves located on the skin's surface while measuring the resulting electrical response of the corresponding muscles.
- Electromyography (EMG)
EMG involves the insertion of small needles into the muscles, allowing for the assessment of muscle activity and detection of characteristic patterns associated with LEMS.
Therapeutics Development of LEMS
- Targets of LEMS Therapy Development
Calcium Influx Recovery Pathway
By specifically targeting voltage-gated calcium or potassium channels, it is possible to restore normal calcium influx and facilitate muscle strength. For example, by blocking certain potassium channels, Amifampridine prolongs the action potential and enhances calcium influx, resulting in increased acetylcholine release. The drug has been approved by the FDA for the therapeutics of LEMS.
- Types of LEMS Therapy Development
Immunomodulatory Therapy
This approach focuses on modulating the autoimmune response in LEMS. Corticosteroids like prednisone are utilized to suppress the immune system and diminish autoantibody production. Additionally, immunomodulators such as azathioprine and mycophenolate mofetil have been explored for their therapeutic potential in LEMS.
Our Services
Our company leads the way in rare disease research and therapeutic development. Our experienced team of scientists and researchers is committed to unraveling the intricacies of LEMS and other rare diseases through the creation of advanced research platforms.
Research Platforms of LEMS
Utilizing cutting-edge technology, our goal is to strategize and develop diagnostics for LEMS to promote early identification and accurate diagnosis of the disease. Our company is actively involved in the development of animal models for LEMS. These models provide us with the ability to develop therapeutics for LEMS, thereby facilitating safety evaluation and pharmacokinetic studies of drug candidates.
| Biological Induction Models | |
|---|---|
| Our scientists conducted injections of antibodies from LEMS individuals into mice, effectively inducing an autoimmune response and successfully establishing a highly accurate LEMS animal model that faithfully replicates the disease process. | |
| Optional Models | LEMS Passive-transfer Model |
| Optional Species | Mice, Guinea Pigs, Others |
If you are interested in our services, please don't hesitate to contact us for more information and a detailed quotation regarding the specific services you require.
References
- Kesner, Vita G., et al. "Lambert-Eaton myasthenic syndrome." Neurologic clinics 36.2 (2018): 379-394.
- Titulaer, Maarten J., Bethan Lang, and Jan JGM Verschuuren. "Lambert–Eaton myasthenic syndrome: from clinical characteristics to therapeutic strategies." The Lancet Neurology 10.12 (2011): 1098-1107.
- Meriney, Stephen D., et al. "Lambert–Eaton myasthenic syndrome: mouse passive‐transfer model illuminates disease pathology and facilitates testing therapeutic leads." Annals of the New York Academy of Sciences 1412.1 (2018): 73-81.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.