141P Spinal muscular atrophy is also a disorder of spermatogenesis

IF 2.7 4区医学 Q2 CLINICAL NEUROLOGY

Neuromuscular Disorders Pub Date : 2024-10-01 DOI:10.1016/j.nmd.2024.07.048

A. Magot , A. Reignier , O. Binois , C. Vuillerot , Y. Péréon , Fermasi Study Group

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引用次数: 0

Abstract

Spinal muscular atrophy (SMA) patients benefit from pre-mRNA splicing modifiers targeting the SMN2 gene, which aims to increase functional SMN production. The animal toxicity affecting spermatogenesis associated with one such treatment raised questions about male SMA patients’ spermatogenesis. This descriptive, cross-sectional study was conducted from June 2022 to July 2023. The study involved adult male patients with genetically confirmed SMA type 2 (SMA2) or SMA3 from 13 French neuromuscular centers. The patients’ general data, motor severity, urological history, exposure to certain factors, parenthood, and spermogram results were obtained. Sixty-eight patients were enrolled (33 SMA2 and 35 SMA3 patients). The two patient cohorts had significantly different motor severity, wheelchair usage duration, weight, and height. Forty-one patients had fertility data (parenthood history and spermogram analyses) and involved 33 spermograms. Fertility disorders were identified in 27 of the 41 patients (65·9%, SMA2: 19 cases (90,4%), SMA3: 8 cases (40%)). Among the patients with available spermograms, 81% (27/33) had abnormal sperm concentration; 40% presented azoospermia. These abnormalities were significantly associated with SMA type (more prevalent in SMA2 patients, p<0·001), disease motor severity, which included age at the loss of walking ability and wheelchair use duration (p<0·001). The Motor Function Measure (MFM) determined that the sperm counts were correlated with disease severity (p<0·01). The fertility disorders were correlated with SMA severity and were particularly evident in SMA2 patients. In SMA2 patients, sperm concentration positively correlated with MFM. The potential contributing factors included prolonged sitting (influencing testicular thermoregulation or hormonal dysfunction) and the role of SMN in germ cell development. This study is the first to link fertility disorders with spermogram abnormalities in SMA males. Understanding spermatogenesis in SMA is crucial, especially with new therapies (e.g. risdiplam). Consequently, conducting systematic spermogram studies prior to SMA treatment is recommended.

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141P 脊髓性肌肉萎缩症也是一种精子发生障碍

脊髓性肌萎缩症（SMA）患者受益于以 SMN2 基因为靶点的前核糖核酸剪接修饰剂，其目的是增加功能性 SMN 的产生。与一种此类治疗相关的影响精子发生的动物毒性引发了有关男性SMA患者精子发生的问题。这项描述性横断面研究于 2022 年 6 月至 2023 年 7 月进行。研究对象包括来自法国 13 家神经肌肉中心的经基因证实的 SMA 2 型（SMA2）或 SMA3 型成年男性患者。研究人员获得了患者的一般数据、运动严重程度、泌尿系统病史、接触某些因素的情况、父母身份和精子图结果。68 名患者（33 名 SMA2 患者和 35 名 SMA3 患者）被纳入研究。两组患者的运动严重程度、使用轮椅的时间、体重和身高均有显著差异。41 名患者有生育数据（生育史和精子图分析），涉及 33 张精子图。41 名患者中有 27 人（65-9%，SMA2：19 例（90.4%），SMA3：8 例（40%））存在生育障碍。在有精子图的患者中，81%（27/33）的患者精子浓度异常；40%的患者出现无精子症。这些异常与 SMA 类型（在 SMA2 患者中更为普遍，p<0-001）、疾病运动严重程度（包括丧失行走能力的年龄和使用轮椅的持续时间，p<0-001）密切相关。运动功能测量（MFM）表明，精子数量与疾病严重程度相关（p<0-01）。生育障碍与 SMA 严重程度相关，在 SMA2 患者中尤为明显。在 SMA2 患者中，精子浓度与 MFM 呈正相关。潜在的致病因素包括久坐（影响睾丸体温调节或荷尔蒙功能障碍）和 SMN 在生殖细胞发育中的作用。这项研究首次将 SMA 男性的生育障碍与精子图异常联系起来。了解 SMA 患者的精子发生至关重要，尤其是在采用新疗法（如利斯替普兰）时。因此，建议在SMA治疗前进行系统的精子图研究。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Neuromuscular Disorders 医学-临床神经学

CiteScore

4.60

自引率

3.60%

发文量

543

审稿时长

53 days

期刊介绍： This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects, such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders.