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. 2024 Dec 20;19(1):476.
doi: 10.1186/s13023-024-03494-2.

Spinal muscular atrophy is also a disorder of spermatogenesis

Armelle Magot  1 , Arnaud Reignier  2 , Olivier Binois  3 , Anne Laure Bedat-Millet  4 , Jean-Baptiste Davion  5 , Louise Debergé  6 , Karima Ghorab  7 , Lucie Guyant  8 , Émilie Laheranne  6 , Pascal Laforet  9   10 , Claire Lefeuvre  9   10 , Martial Mallaret  11 , Maud Michaud  12 , Chahla Omar  9   10 , Aleksandra Nadaj-Pakleza  13 , Guillaume Nicolas  9   10 , Jean Baptiste Noury  14 , Antoine Pegat  15 , Morgane Péré  16 , Emmanuelle Salort-Campana  17 , Guilhem Sole  6 , Marco Spinazzi  18 , Céline Tard  5 , Carole Vuillerot  19   20   21 , Yann Péréon  22
Affiliations

Spinal muscular atrophy is also a disorder of spermatogenesis

Armelle Magot et al. Orphanet J Rare Dis. .

Abstract

Background: 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.

Methods: 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. All patients were enrolled prior to exposure to risdiplam.

Findings: Sixty-eight patients were enrolled ( 36 SMA2 and 32 SMA3 patients). Forty-one patients had fertility data (parenthood history and spermogram analyses) and underwent 33 spermograms. Fertility disorders were identified in 27 of the 41 patients (65·9%, 95%CI 51·3-80·4%) in particular SMA2 patients: 19 cases (90.5%, CI 77·9-100%) (SMA3: 8 cases (40%, CI 18·5-61·5%). Among the patients with available spermograms, 81% (27/33) had abnormal sperm concentration; 30% 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 also correlated with disease severity (p < 0·01).

Interpretation: The fertility disorders were correlated with SMA severity and were particularly evident in SMA2 patients. In the latter, sperm concentration positively correlated with MFM. This study is the first one to link fertility disorders with spermogram abnormalities in SMA males. Understanding spermatogenesis in SMA is crucial, especially with new therapies such as risdiplam. Consequently, conducting systematic spermogram studies prior to SMA treatment is recommended.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The relevant French non-interventional research committee (GNEDS) approved the study. Consent for publication: Not Applicable. Competing interests: AM has received honoraria from lectures for Biogen. JBD, YP, ESC, PL and ADP have received honoraria from advisory board and lectures for Roche and Biogen. JBN has participated at scientific congress sponsoring from Biogen and Novartis. GS has received financial support from Roche and Biogen and participated at scientific congress sponsoring from Biogen and Roche. CT, ALBM have received personal fees and non-financial support from Roche and Biogen. All these competing interest are outside the submitted work. AR, OB, LD, KG, LG, EL, CL, MM, MM, CO, GN, AP, MP, MS, CV have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of patient division into the three groups
Fig. 2
Fig. 2
Scatter Plot of correlations between sperm concentration with MFM, RULM and duration of wheelchair use
See this image and copyright information in PMC

References

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