Heatwole Chad Rydel, Luebbe Elizabeth, Hamel Johanna, Mongiovi Phillip C, Ciafaloni Emma, Dilek Nuran, Martens William B, Weber David R, Rashid Hani, Allen McKeown Jamie, Smith Claire H, Howell Samantha, Rosero Spencer Z, Eichinger Katy, Baker Lindsay S, Dekdebrun Jeanne M, Hilbert James E, Varma Anika, Thornton Charles A, McDermott Michael P, Moxley Richard T
Department of Neurology, University of Rochester, NY.
The Center for Health + Technology (CHeT), Rochester, NY.
Neurol Genet. 2025 Aug 27;11(5):e200292. doi: 10.1212/NXG.0000000000200292. eCollection 2025 Oct.
Effective therapies for facioscapulohumeral muscular dystrophy (FSHD) are currently limited. Recombinant human growth hormone (rHGH) combined with testosterone (combination therapy) may have meaningful clinical effects on ambulation, strength, muscle mass, and disease burden. As such, combination therapy has the potential to limit disease progression and functional decline in individuals with muscular dystrophy. The objective of this study was to evaluate the safety, tolerability, and potential efficacy of combination therapy in adult men with FSHD.
This investigator-initiated, single-center (University of Rochester), single-arm, proof-of-concept study evaluated the safety and tolerability of combination therapy in ambulatory adult men with FSHD. Participants received daily rHGH combined with testosterone enanthate injections every 2 weeks for 24 weeks, followed by a 12-week washout period. Participants underwent serial safety and laboratory assessments to monitor safety and tolerability during the study. Participants were also evaluated for changes from baseline in lean body mass (LBM) and fat mass, measured by dual-energy X-ray absorptiometry; ambulation, measured by 6-minute walk distance; strength; clinical function, measured using the FSHD-Composite Outcome Measure (FSHD-COM); and patient-reported disease burden, measured by the FSHD Health Index (FSHD-HI).
Nineteen of 20 participants completed the study, with no participants experiencing a serious adverse event. The most common adverse event was mild injection site reaction at the rHGH and/or testosterone injection site. After 24 weeks, LBM improved by 2.21 kilograms (95% CI 1.35-3.07; < 0.0001), fat mass decreased by 1.30 kilograms (95% CI -2.56 to -0.04; = 0.04), 6-minute walk distance increased by 37.3 m (95% CI 18.3-56.9; = 0.001), overall strength (average % of predicted normal) increased by 3% (95% CI 0.3-5.6; = 0.03), clinical function (FSHD-COM) improved by 2.4 points (95% CI 4.0-0.8; = 0.006), and total disease burden (FSHD-HI) decreased by 6.1 points (95% CI -12.0 to -0.2; = 0.04).
Combination therapy was safe and well tolerated in men with FSHD. Participants experienced improvements in ambulation, strength, muscle mass, and disease burden after receiving this study intervention. Larger randomized, double-blind, placebo-controlled trials are needed to further investigate this promising therapeutic approach.
Registered on ClinicalTrials.gov: NCT03123913.
目前，面肩肱型肌营养不良（FSHD）的有效治疗方法有限。重组人生长激素（rHGH）联合睾酮（联合治疗）可能对行走能力、力量、肌肉质量和疾病负担产生有意义的临床效果。因此，联合治疗有可能限制肌营养不良患者的疾病进展和功能衰退。本研究的目的是评估联合治疗对成年男性FSHD患者的安全性、耐受性和潜在疗效。
本由研究者发起、单中心（罗切斯特大学）、单臂、概念验证研究评估了联合治疗对能够行走的成年男性FSHD患者的安全性和耐受性。参与者每天接受rHGH治疗，并每2周注射一次庚酸睾酮，持续24周，随后是12周的洗脱期。在研究期间，参与者接受了一系列安全性和实验室评估，以监测安全性和耐受性。还通过双能X线吸收法评估了参与者瘦体重（LBM）和脂肪量相对于基线的变化；通过6分钟步行距离评估行走能力；评估力量；使用FSHD综合结局测量（FSHD-COM）评估临床功能；通过FSHD健康指数（FSHD-HI）评估患者报告的疾病负担。
20名参与者中有19名完成了研究，没有参与者发生严重不良事件。最常见的不良事件是rHGH和/或睾酮注射部位的轻度注射部位反应。24周后，LBM增加了kg（95%CI1.35-3.07；<0.0001），脂肪量减少了1.30kg（95%CI-2.56至-0.04；=0.04），6分钟步行距离增加了37.3m（95%CI18.3-56.9；=0.001），总体力量（预测正常平均值的百分比）增加了3%（95%CI）0.3-5.
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