Male Reproduction in Spinal Muscular Atrophy (SMA) and the Potential Impact of Oral Survival of Motor Neuron 2 (SMN2) Pre-mRNA Splicing Modifiers.

IF 3.9 3区医学 Q1 CLINICAL NEUROLOGY Neurology and Therapy Pub Date : 2024-08-01 Epub Date: 2024-05-16 DOI:10.1007/s40120-024-00626-5

Natan Bar-Chama, Bakri Elsheikh, Channa Hewamadduma, Carol Jean Guittari, Ksenija Gorni, Lutz Mueller

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Abstract

Spinal muscular atrophy (SMA) is a neuromuscular disease caused by deletions or mutations in the survival of motor neuron 1 (SMN1) gene resulting in reduced levels of SMN protein. SMN protein is produced by cells throughout the body, and evidence suggests that low SMN protein can have systemic implications, including in male reproductive organs. However, a paucity of research exists on this important topic. This article will discuss findings from non-clinical studies on the role of SMN in the male reproductive system; additionally, real-world observational reports of individuals with SMA will be examined. Furthermore, we will review the non-clinical reproductive findings of risdiplam, a small-molecule SMN2 splicing modifier approved for the treatment of SMA, which has widespread distribution in both the central nervous system and peripheral organs. Specifically, the available non-clinical evidence of the effect of risdiplam on male reproductive organs and spermatogenesis is examined. Lastly, the article will highlight available capabilities to assess male fertility as well as the advanced reproductive technologies utilized to treat male infertility. This article demonstrates the need for further research to better understand the impacts of SMA on male fertility and reproduction.

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脊髓性肌肉萎缩症（SMA）的男性生殖和运动神经元 2 (SMN2) 前核糖核酸剪接修饰物口服存活的潜在影响。

脊髓性肌萎缩症（SMA）是一种神经肌肉疾病，由运动神经元 1（SMN1）生存基因缺失或突变导致 SMN 蛋白水平降低引起。SMN蛋白由全身细胞产生，有证据表明，SMN蛋白含量低会对包括男性生殖器官在内的全身器官产生影响。然而，关于这一重要课题的研究还很少。本文将讨论有关 SMN 在男性生殖系统中作用的非临床研究结果；此外，还将研究有关 SMA 患者的真实世界观察报告。此外，我们还将回顾利斯地平的非临床生殖研究结果，利斯地平是一种小分子 SMN2 剪接修饰剂，已被批准用于治疗 SMA，它广泛分布于中枢神经系统和外周器官。文章特别研究了利斯地平对男性生殖器官和精子生成影响的现有非临床证据。最后，文章将重点介绍评估男性生育能力的现有能力以及用于治疗男性不育症的先进生殖技术。本文表明，有必要开展进一步研究，以更好地了解 SMA 对男性生育能力和生殖的影响。

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来源期刊

Neurology and Therapy CLINICAL NEUROLOGY-

CiteScore

5.40

自引率

8.10%

发文量

103

审稿时长

6 weeks

期刊介绍： Aims and Scope Neurology and Therapy aims to provide reliable and inclusive, rapid publication for all therapy related research for neurological indications, supporting the timely dissemination of research with a global reach, to help advance scientific discovery and support clinical practice. Neurology and Therapy is an international, open access, peer reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world and health outcomes research around the discovery, development, and use of neurological and psychiatric therapies, (also covering surgery and devices). Studies relating to diagnosis, pharmacoeconomics, public health, quality of life, and patient care, management, and education are also welcomed. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, case reports, trial designs, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Neurology and Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research. Rapid Publication The journal’s rapid publication timelines aim for a peer review decision within 2 weeks of submission. If an article is accepted, it will be published online 3-4 weeks from acceptance. These rapid timelines are achieved through the combination of a dedicated in-house editorial team, who closely manage article workflow, and an extensive Editorial and Advisory Board who assist with rapid peer review. This allows the journal to support the rapid dissemination of research, whilst still providing robust peer review. Combined with the journal’s open access model, this allows for the rapid and efficient communication of the latest research and reviews to support scientific discovery and clinical practice. Open Access All articles published by Neurology and Therapy are open access. Personal Service The journal’s dedicated in-house editorial team offer a personal “concierge service” meaning that authors will always have a personal point of contact able to update them on the status of their manuscript. The editorial team check all manuscripts to ensure that articles conform to the most recent COPE and ICMJE publishing guidelines. This supports the publication of ethically sound and transparent research. We also encourage pre-submission enquiries and are always happy to provide a confidential assessment of manuscripts. 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Peer Review Process Upon submission, manuscripts are assessed by the editorial team to ensure they fit within the aims and scope of the journal and are also checked for plagiarism. All suitable submissions are then subject to a comprehensive single-blind peer review. Reviewers are selected based on their relevant expertise and publication history in the subject area. The journal has an extensive pool of editorial and advisory board members who have been selected to assist with peer review based on the afore-mentioned criteria. At least two extensive reviews are required to make the editorial decision, with the exception of some article types such as Commentaries, Editorials and Letters which are generally reviewed by one member of the Editorial Board. Where reviews conflict, an Editorial Board Member will be contacted for further advice and a presiding decision. Manuscripts are then either accepted, rejected or authors are required to make major or minor revisions (both reviewer comments and editorial comments may need to be addressed. Once a revised manuscript is re-submitted, it is assessed along with the responses to reviewer comments and if it has been adequately revised, it will be accepted for publication. Accepted manuscripts are then copyedited and typeset by the production team before online publication. Appeals against decisions following peer review are considered on a case-by-case basis and should be sent to the journal editor, and authors are welcome to make rebuttals against individual reviewer comments, if appropriate. Preprints We encourage posting of preprints of primary research manuscripts on preprint servers, authors'' or institutional websites, and open communications between researchers whether on community preprint servers or preprint commenting platforms. 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