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一种肌肉生长抑制素拮抗剂在患有心脏恶病质犬中的初步研究。

Pilot study of a myostatin antagonist in dogs with cardiac cachexia.

作者信息

Freeman Lisa M, Rush John E, Cunningham Suzanne M, Yang Vicky K, Bulmer Barret J

机构信息

Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA.

Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA.

出版信息

J Vet Cardiol. 2015 Sep;17(3):210-5. doi: 10.1016/j.jvc.2015.06.004. Epub 2015 Sep 26.

DOI:10.1016/j.jvc.2015.06.004
PMID:26412784
Abstract

OBJECTIVES

Cardiac cachexia, a loss of lean body mass caused by heart disease, often accompanies congestive heart failure (CHF). Blocking myostatin, which is a protein that inhibits muscle growth, appears to greatly enhance muscle size and strength in rodent models and human clinical trials. The objective of this study was to evaluate a dog-specific myostatin antagonist (CAP-031) in a pilot study to test its safety and efficacy in dogs with CHF and cardiac cachexia.

ANIMALS

Dogs with CHF and cardiac cachexia.

METHODS

Eligible dogs received four weekly subcutaneous injections of CAP-031. Endpoints were body weight, body condition score (BCS, on a 1-9 scale), muscle condition score (MCS, on a five-point scale, where 0 = no muscle loss and 4 = severe muscle loss), appetite, and a quality of life (QOL) score.

RESULTS

Seven dogs with CHF and moderate-to-severe cachexia were enrolled in the study. For the six dogs that completed the study, the median age was 8.8 years (range 6.4-10.6). At baseline, the median body weight was 27.0 kg (range 17.3-62.0), the median BCS was 4 (2-5), and median MCS was 3 (3-4). There were no significant changes in body weight, BCS, appetite, or QOL score. The change in MCS (from a median of 3 at baseline to a median of 2.5 at week 4) was not statistically significant (p = 0.06).

CONCLUSIONS

The myostatin antagonist appeared to be well tolerated in most dogs. Earlier identification of cachexia is important, and randomized, controlled trials of myostatin antagonists or other drugs to treat cardiac cachexia are needed.

摘要

目的

心脏恶病质是一种由心脏病导致的瘦体重丢失,常伴随充血性心力衰竭(CHF)出现。在啮齿动物模型和人类临床试验中,抑制肌肉生长的蛋白质——肌生成抑制素的阻断似乎能显著增加肌肉大小和力量。本研究的目的是在一项初步研究中评估一种针对犬类的肌生成抑制素拮抗剂(CAP - 031),以测试其对患有CHF和心脏恶病质的犬类的安全性和有效性。

动物

患有CHF和心脏恶病质的犬类。

方法

符合条件的犬类每周接受一次CAP - 031皮下注射,共注射四周。观察指标包括体重、身体状况评分(BCS,1 - 9分制)、肌肉状况评分(MCS,五分制,0表示无肌肉丢失,4表示严重肌肉丢失)、食欲和生活质量(QOL)评分。

结果

七只患有CHF和中度至重度恶病质的犬类被纳入研究。完成研究的六只犬类的中位年龄为8.8岁(范围6.4 - 10.6岁)。基线时,中位体重为27.0千克(范围17.3 - 62.0千克),中位BCS为4(2 - 5),中位MCS为3(3 - 4)。体重、BCS、食欲或QOL评分均无显著变化。MCS的变化(从基线时的中位值3变为第4周时的中位值2.5)无统计学意义(p = 0.06)。

结论

肌生成抑制素拮抗剂在大多数犬类中似乎耐受性良好。早期识别恶病质很重要,需要进行肌生成抑制素拮抗剂或其他治疗心脏恶病质药物的随机对照试验。

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