Christos Koros, Athina-Maria Simitsi, Nikolaos Papagiannakis, Anastasia Bougea, Roubina Antonelou, Ioanna Pachi, Evangelos Sfikas, Evangelia Stanitsa, Efthalia Angelopoulou, Vasilios C Constantinides, Sokratis G Papageorgiou, Constantin Potagas, Maria Stamelou, Leonidas Stefanis
{"title":"携带常染色体隐性基因变异的帕金森病患者队列中的多巴胺能精准治疗:临床队列数据和小型综述。","authors":"Christos Koros, Athina-Maria Simitsi, Nikolaos Papagiannakis, Anastasia Bougea, Roubina Antonelou, Ioanna Pachi, Evangelos Sfikas, Evangelia Stanitsa, Efthalia Angelopoulou, Vasilios C Constantinides, Sokratis G Papageorgiou, Constantin Potagas, Maria Stamelou, Leonidas Stefanis","doi":"10.3390/neurolint16040062","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce.</p><p><strong>Methods: </strong>Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous <i>PRKN</i> carriers, four heterozygous <i>PRKN</i> carriers, and three biallelic <i>PINK1</i> carriers) were evaluated.</p><p><strong>Results: </strong>The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in <i>PRKN</i> carriers and 765 ± 96.6 (range 660-850) in <i>PINK1</i> carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 <i>PRKN</i> and 1/3 <i>PINK1</i> carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs.</p><p><strong>Conclusions: </strong>In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.</p>","PeriodicalId":19130,"journal":{"name":"Neurology International","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11356784/pdf/","citationCount":"0","resultStr":"{\"title\":\"Precision Dopaminergic Treatment in a Cohort of Parkinson's Disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review.\",\"authors\":\"Christos Koros, Athina-Maria Simitsi, Nikolaos Papagiannakis, Anastasia Bougea, Roubina Antonelou, Ioanna Pachi, Evangelos Sfikas, Evangelia Stanitsa, Efthalia Angelopoulou, Vasilios C Constantinides, Sokratis G Papageorgiou, Constantin Potagas, Maria Stamelou, Leonidas Stefanis\",\"doi\":\"10.3390/neurolint16040062\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce.</p><p><strong>Methods: </strong>Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous <i>PRKN</i> carriers, four heterozygous <i>PRKN</i> carriers, and three biallelic <i>PINK1</i> carriers) were evaluated.</p><p><strong>Results: </strong>The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in <i>PRKN</i> carriers and 765 ± 96.6 (range 660-850) in <i>PINK1</i> carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 <i>PRKN</i> and 1/3 <i>PINK1</i> carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs.</p><p><strong>Conclusions: </strong>In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.</p>\",\"PeriodicalId\":19130,\"journal\":{\"name\":\"Neurology International\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11356784/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurology International\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3390/neurolint16040062\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurology International","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3390/neurolint16040062","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Precision Dopaminergic Treatment in a Cohort of Parkinson's Disease Patients Carrying Autosomal Recessive Gene Variants: Clinical Cohort Data and a Mini Review.
Introduction: Parkinson's disease (PD) patients harboring recessive gene variants exhibit a distinct clinical phenotype with an early disease onset and relatively mild symptoms. Data concerning individualized therapy for autosomal recessive PD forms are still scarce.
Methods: Demographic and treatment data of a cohort of PD carriers of recessive genes (nine homozygous or compound heterozygous PRKN carriers, four heterozygous PRKN carriers, and three biallelic PINK1 carriers) were evaluated.
Results: The average levodopa equivalent daily dose (LEDD) was 806.8 ± 453.5 (range 152-1810) in PRKN carriers and 765 ± 96.6 (range 660-850) in PINK1 carriers. The majority responded to low/moderate doses of levodopa. The response to dopamine agonists (DAs) was often favorable both as initial and longitudinal therapy. In total, 8/13 PRKN and 1/3 PINK1 carriers were treated with amantadine successfully, and this also applied to patients who could not tolerate levodopa or DAs.
Conclusions: In the era of personalized treatment, the therapeutic approach in recessive PD gene carriers might differ as compared to idiopathic PD. Lower LEDD doses were efficient even in patients with a very long disease duration, while a few patients were doing well without any levodopa treatment decades after disease initiation. DAs or amantadine could be used as a first and main line treatment regimen if well tolerated. Literature data on therapeutic strategies in carriers of pathogenic mutations in recessive PD genes, including device-aided treatments, will be further discussed.