NAA and Lambert-Eaton Muscular Weakness Syndrome

The discovery of pathogenic autoantibodies targeting voltage-gated calcium channels (VGCC) in the presynaptic membrane of nerve endings confirms that Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease of the neuromuscular junction (NMJ) and improves our understanding of its pathophysiological mechanisms. The detection of functional VGCCs on the surface of small cell lung cancer (SCLC) further provided an etiological basis for LEMS. Creative Biolabs is a premier natural autoantibodies (NAA) services provider in the United States, our experts can help you from the very first idea, by providing expert consultancy in the design of your research.

Description of LEMS

LEMS is a neuromuscular autoimmune disease. In LEMS, the characteristic muscle weakness is thought to be caused by pathogenic autoantibodies against VGCC at the presynaptic nerve terminal. LEMS is divided into two main subgroups: LEMS with SCLC and LEMS without SCLC. Typical clinical symptoms of LEMS include the typical distribution of triad weakness, reflexes, and autonomic dysfunction. The specificity of VGCC autoantibodies is very high, confirming the diagnosis of LEMS. SOX antibodies are an additional marker for the diagnosis of LEMS disease because they are highly specific for SCLC but have low sensitivity.

LEMS Develop Pathway

LEMS is caused by autoantibodies to VGCC in the membrane of presynaptic neuronal cells. This antibody exhibits high sensitivity and is detected in 85% of all LEMS patients. The VGCC antibodies in LEMS lead to a reduced quantitative release of acetylcholine. The autonomic dysfunction in LEMS may be identical to VGCC antibodies that cause muscle weakness. Antibodies impair parasympathetic and sympathetic transmitter release by down-regulating receptors. VGCC mediates the influx of calcium into the nerve terminal. This influx activates presynaptic signaling pathways leading to the release of neurotransmitter vesicles at distinct synaptic vesicle release sites, which are known as "active zones". LEMS antibodies lead to loss of VGCC function by blocking calcium influx during depolarization and/or down-regulating VGCCs, resulting in reduced acetylcholine release from the presynaptic membrane. Further reduction of neurotransmitter release is thought to be caused by a reduction in the number of active zones.

Fig.1 Pathophysiology of LEMS. (Giannoccaro, Patrizia and Rocco, 2021)Fig.1 The changes of neuromuscular junction in LEMS.1

NAA Services for LEMS at Creative Biolabs

LEMS Related Products at Creative Biolabs

Creative Biolabs provides a wide range of NAA detection kits which are considered particularly powerful tools for studying disease pathways, screening for potential drug candidates, and evaluating biopharmaceutical production processes.

A better understanding of the pathophysiological mechanisms of LEMS has contributed to the development of new diagnostic methods and has led to targeted symptomatic and immunosuppressive therapies. With over 10 years of custom NAA services experience, Creative Biolabs prides itself on being an innovator and problem solver in the NAA industry. If you are interested in our services and products, please contact us for more information.

Reference

  1. Giannoccaro, Maria Pia, Patrizia Avoni, and Rocco Liguori. "Presynaptic paraneoplastic disorders of the neuromuscular junction: an update." Brain Sciences 11.8 (2021): 1035.
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