5年N-of-1生长激素释放激素基因治疗实验结果

IF 2.2 4区 医学 Q3 GERIATRICS & GERONTOLOGY Rejuvenation research Pub Date : 2021-12-01 DOI:10.1089/rej.2021.0036
Brian P Hanley, Keith Brewer, George Church
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引用次数: 1

摘要

本文首次提出的结果显示,在一个接受激素基因治疗的人身上,持续了5年以上的时间。该生长激素释放激素(GHRH)治疗分两次给药,间隔一年,第二次给药后平均195 ng/mL (13 ×正常人,σ = 143, σ m = 34, max = 495, min = 53)。这种水平的GHRH治疗似乎对受试者是安全的,尽管有一些不良事件。胰岛素样生长因子1水平几乎没有受到影响,生长激素测试结果也没有受到影响,使用的激素同系物没有显示肢端肥大症的迹象。心率下降8 - 13次/分钟,持续5年以上。睾酮水平上升了52% (σ = 22%, σ m = 6%)。高密度脂蛋白/低密度脂蛋白比值由3.61降至平均2.81 (σ = 0.26, σ m = 0.057, max = 3.3, min = 2.5),甘油三酯由196 mg/dL降至平均94.4 mg/dL (σ = 21.9, σ m = 5.0, min = 59, max = 133, min = 59)。然而,白细胞计数增加,基线并不强。CD4和CD8意味着增加by11.7%(σ= 11.6%,σM = 3.3%, max = 30.7%,最小值= -9.6%)和12.0%(σ= 10.5%,σM = 3.0%, max = 29.1%,最小值= -6.7%),分别为。辅助观察包括早期的欣快感,以及第一次剂量后视力矫正的显着改善,球面矫正从基线(L/R) -2.25/-2.75到-0.25/-0.5。在接下来的5年里,修正回落至-1.25/-1.75。治疗后Horvath表型降低44.1%。完成时,表观遗传年龄为-6年(-9.3%),端粒年龄为+7个月(+0.9%)。
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Results of a 5-Year N-of-1 Growth Hormone Releasing Hormone Gene Therapy Experiment.

Here presented for the first time are results showing persistence over a 5+ year period in a human who had a hormone gene therapy administered to muscle. This growth hormone releasing hormone (GHRH) therapy was administered in two doses, a year apart, with a mean after the second dose of 195 ng/mL (13 × normal, σ = 143, σM = 34, max = 495, min = 53). This level of GHRH therapy appears to be safe for the subject, although there were some adverse events. Insulin-like growth factor 1 levels were little affected, nor were the growth hormone test results, showing no indications of acromegaly for the hormone homologue used. Heart rate declined 8 to 13 bpm, persistent over 5 years. Testosterone rose by 52% (σ = 22%, σM = 6%). The high-density lipoprotein/low-density lipoprotein ratio dropped from 3.61 to mean 2.81 (σ = 0.26, σM = 0.057, max = 3.3, min = 2.5), and triglycerides declined from 196 mg/dL to mean 94.4 mg/dL (σ = 21.9, σM = 5.0, min = 59, max = 133, min = 59). White blood cell counts increased, however, the baseline was not strong. CD4 and CD8 mean increased by11.7% (σ = 11.6%, σM = 3.3%, max = 30.7%, min = -9.6%) and 12.0% (σ = 10.5%, σM = 3.0%, max = 29.1%, min = -6.7%), respectively. Ancillary observations comprise an early period of euphoria, and a dramatic improvement in visual correction after the first dose, spherical correction from baseline (L/R) -2.25/-2.75 to -0.25/-0.5. Over the next 5 years, correction drifted back to -1.25/-1.75. Horvath PhenoAge was cut 44.1% post-treatment. At completion, epigenetic age was -6 years (-9.3%), and telomere age was +7 months (+0.9%).

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来源期刊
Rejuvenation research
Rejuvenation research 医学-老年医学
CiteScore
4.50
自引率
0.00%
发文量
41
审稿时长
3 months
期刊介绍: Rejuvenation Research publishes cutting-edge, peer-reviewed research on rejuvenation therapies in the laboratory and the clinic. The Journal focuses on key explorations and advances that may ultimately contribute to slowing or reversing the aging process, and covers topics such as cardiovascular aging, DNA damage and repair, cloning, and cell immortalization and senescence. Rejuvenation Research coverage includes: Cell immortalization and senescence Pluripotent stem cells DNA damage/repair Gene targeting, gene therapy, and genomics Growth factors and nutrient supply/sensing Immunosenescence Comparative biology of aging Tissue engineering Late-life pathologies (cardiovascular, neurodegenerative and others) Public policy and social context.
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