Category: Choreas (Non-Huntington's Disease)
Objective: Autoimmune chorea (AICh) resulting from the appearance of paraneoplastic antibodies in response to development of malignant tumors of various localization. Sydenham’s rheumatic chorea, described in 1686, is one of the AICh forms. Given that similarity of a number of symptoms of AICh and Sindengham’s chorea, including hyperkinesis and a number of mental disorders.
Background: Parainfectious, paraneoplastic and idiopathic varieties of autoimmune chorea are known. Dysfunction of neurons in the basal ganglia, which provide fine regulation of movements, occurs in response to the production of specific auto-antibodies against these structures.
Method: 26 patients, in whom in 72 percent of cases malignant tumors of various localization were detected. of the examined by us suffered from various hyperkinesis in the form of athetosis, akathisia, ballism, dystonia, facial hemispasm and myoclonus. In 84 percent of these patients, antibodies to NMDAR, CASPR2 and LGI1 were determined. AC syndromes were modeled on mice by introducing stereotaxically antistreptococcal antibodies into the striatum of white mice. We used transgenic models of chorea in mice with KCNMA1 mutation, providing hyperkinetic phenomena. In this way, stable mouse models were obtained that mimic symptoms of choreic hyperkinesis in humans suffering from this severe extrapyramidal pathology.
Results: In 79 percent of the experimental models of chorea, an increase in the concentration of antibodies to NMDAR and CASPR2, containing the integrin protein contactin, was also detected in patients with autoimmune choreic hyperkinesis. Approximately same percentage of patients with autoimmune chorea also showed similar increases in titer of these antibodies. We used pepinemab, a monoclonal antibody (MAB) that blocks the semaphorin protein involved in axonal guidance signaling. In 84 percent of patients and 76 percent of experimental animals, was a significant decrease in hyperkinesis. Patients with AICh showed a decrease in tremor, muscle rigidity, almost complete disappearance of hemiballismus.
Conclusion: The use of MAB for the treatment of AICh seems to be a logical, rational and justified method of therapy, given the production of own autoantibodies to a number of structures of the nervous system, including synapses, neurotransmitter receptors and ion channels, which is one of the main mechanisms for development of this severe pathology of movement disorders.
References: 1. Davis, Rebecca; Dalmau, Josep (September 2013). “Autoimmunity, seizures, and status epilepticus”. Epilepsia. 54 (6): 46–49. doi:10.1111/epi.12276. PMC 3767193. PMID 24001072.
2. Tobin, William Oliver; Lennon, Vanda A.; Komorowski, Lars; Probst, Christian; Clardy, Stacey Lynn; Aksamit, Allen J.; Appendino, Juan Pablo; Lucchinetti, Claudia F.; Matsumoto, Joseph Y.; Pittock, Sean J.; Sandroni, Paola; Tippmann-Peikert, Maja; Wirrell, Elaine C.; McKeon, Andrew (11 November 2014). “DPPX potassium channel antibody: Frequency, clinical accompaniments, and outcomes in 20 patients”. Neurology. 83 (20): 1797–1803. doi:10.1212/WNL.0000000000000991. ISSN 0028-3878. PMC 4240433. PMID 25320100.
3. Dalmau, Josep; Tüzün, Erdem; Wu, Hai-yan; Masjuan, Jaime; Rossi, Jeffrey E.; Voloschin, Alfredo; Baehring, Joachim M.; Shimazaki, Haruo; Koide, Reiji; King, Dale; Mason, Warren; Sansing, Lauren H.; Dichter, Marc A.; Rosenfeld, Myrna R.; Lynch, David R. (January 2007). “Paraneoplastic anti- N -methyl-D-aspartate receptor encephalitis associated with ovarian teratoma”. Annals of Neurology. 61 (1): 25–36. doi:10.1002/ana.21050. PMC 2430743. PMID 17262855.
4. Graus, Francesc; Titulaer, Maarten J.; Balu, Ramani; Benseler, Susanne; Bien, Christian G.; Cellucci, Tania; Cortese, Irene; Dale, Russell C.; Gelfand, Jeffrey M.; Geschwind, Michael; Glaser, Carol A.; Honnorat, Jerome; Höftberger, Romana; Iizuka, Takahiro; Irani, Sarosh R. (1 April 2016). “A clinical approach to diagnosis of autoimmune encephalitis”. The Lancet Neurology. 15 (4): 391–404. doi:10.1016/S1474-4422(15)00401-9. ISSN 1474-4422. PMC 5066574. PMID 26906964
To cite this abstract in AMA style:
D. Labunskiy, S. Kiryukhina, D. Kuzmin, V. Podsevatkin. Autoimmune Chorea. Therapy with Monoclonal Antibodies: Experimental and Clinical Approach [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/autoimmune-chorea-therapy-with-monoclonal-antibodies-experimental-and-clinical-approach/. Accessed May 23, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/autoimmune-chorea-therapy-with-monoclonal-antibodies-experimental-and-clinical-approach/