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首例针对多态性多巴胺D2(-DRD2/ANKK(Taq1A))、OPRM1(A/G)、DRD3(C/T)和MAOA(4R)基因缺陷的青春期前男性疑似熊猫症/儿童自身免疫性神经精神障碍相关性疾病患者进行的神经精神症状的首次试点表观遗传类型改善:精准DNA检测及促多巴胺调节(KB220)和抗菌治疗带来的积极临床结果

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies.

作者信息

Blum Kenneth, Elman Igor, Han David, Hanna Colin, Baron David, Gupta Ashim, Kazmi Shan, Khalsa Jag, Bagchi Debasis, McLaughlin Thomas, Badgaiyan Rajendra D, Modestino Edward J, Edwards Drew, Dennen Catherine A, Braverman Eric R, Bowirrat Abdalla, Sunder Keerthy, Murphy Kevin, Jafari Nicole, Zeine Foojan, Carney Paul R, Gold Mark S, Lewandowski Kai-Uwe, Sharafshah Alireza, Pollack Aryeh R, Thanos Panayotis K

机构信息

Division of Addiction Research & Education, Center for Sports and Mental Health, Western University of Health Sciences, Pomona, CA, USA.

Department of Psychiatry, Boonshoft School of Medicine, Wright State University and Dayton VA Medical Centre, Dayton, OH, USA.

出版信息

Open J Immunol. 2024 Sep;14(3):60-86. doi: 10.4236/oji.2024.143006.

Abstract

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN) to help induce "dopamine homeostasis" in patients with PANDAS, especially those with known DNA-induced hypodopaminergia. This case study examines a 12-year-old Caucasian male with no prior psychiatric issues who presented with a sudden onset of severe anxiety, depression, emotional liability, and suicidal ideation. The patient underwent genotyping and the genetic addiction risk score (GARS) testing, which revealed risk polymorphisms in the dopamine D2 (-DRD2/ANKK (Taq1A), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) genes. These polymorphisms have been linked to hypodopaminergia. The patient was subsequently placed on research ID-KB220ZPBMPOLY (POLYGEN), and albeit the possibility of bias, based upon self and parental assessment, a marked rapid improvement in psychiatric symptoms was observed. In the second phase of treatment (102 days utilizing KB220), the patient received standard antibody testing, which was positive for Lyme. Antibacterial therapy started immediately, and KB220z was discontinued to provide a wash-out period. A monotonic trend analysis was performed on each outcome measure, and a consistently decreasing trend was observed utilizing antibacterial therapy. Our recommendation, albeit only one case, is to utilize and further research a combined therapeutic approach, involving precision-guided DNA testing and pro-dopamine regulation along with antibacterial therapy, as well as glutathione to address offensive enhanced cytokines, in patients with suspected PANDAS/CANS.

摘要

与链球菌及其他细菌感染相关或无关的儿童自身免疫性神经精神疾病(PANDAS/CANS)正逐渐成为一种典型的儿童疾病。尽管在治疗方法上存在一些争议,尤其是与行为后遗症相关的争议,但我们在其他已发表的研究中推测,它的特征是儿童中奖赏缺乏综合征(RDS)的快速发作。我们建议采用一种多系统生物学方法,将基因成瘾风险测试与多巴胺前体调节(KB220/POLYGEN)相结合,以帮助诱导PANDAS患者,尤其是那些已知存在DNA诱导的多巴胺功能减退的患者实现“多巴胺稳态”。本病例研究考察了一名12岁的白种男性,他之前没有精神疾病问题,却突然出现严重焦虑、抑郁、情绪易激惹和自杀观念。该患者接受了基因分型和基因成瘾风险评分(GARS)测试,结果显示多巴胺D2(-DRD2/ANKK(Taq1A)、OPRM1(A/G)、DRD3(C/T)和MAOA(4R)基因存在风险多态性。这些多态性与多巴胺功能减退有关。该患者随后接受了研究用ID-KB220ZPBMPOLY(POLYGEN)治疗,尽管存在偏差的可能性,但根据患者自身及家长的评估,观察到其精神症状有明显快速改善。在治疗的第二阶段(使用KB220治疗102天),患者接受了标准抗体检测,结果显示莱姆病呈阳性。立即开始抗菌治疗,并停用KB220z以提供一个洗脱期。对每个结局指标进行了单调趋势分析,结果显示使用抗菌治疗后呈持续下降趋势。尽管这只是一个病例,但我们的建议是,对于疑似PANDAS/CANS的患者,采用并进一步研究一种联合治疗方法,包括精准指导的DNA检测、多巴胺前体调节、抗菌治疗以及使用谷胱甘肽来应对攻击性增强的细胞因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ae2a/11539193/f1f22b48100c/nihms-2026239-f0001.jpg

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