KLF4 modulators(Kruppel-like factor 4 modulators)、POU5F1 modulators(POU class 5 homeobox 1 modulators)、SOX2 modulators(SRY-box transcription factor 2 modulators)

治疗领域

眼部疾病

在研适应症

青光眼

非在研适应症-

原研机构

Life Biosciences, Inc.初创企业

在研机构

Life Biosciences, Inc.初创企业

非在研机构-

最高研发阶段临床前

首次获批日期-

最高研发阶段(中国)-

特殊审评-

关联

100 项与 ER-100 相关的临床结果

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100 项与 ER-100 相关的转化医学

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100 项与 ER-100 相关的专利（医药）

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项与 ER-100 相关的文献（医药）

2016-12-01·British journal of pharmacology2区 · 医学

Functional pharmacological characterization of SER100 in cardiovascular health and disease

2区 · 医学

Article

作者: Moyes, Amie J ; Gulbrandsen, Trygve ; Steiness, Eva ; Hobbs, Adrian J ; Villar, Inmaculada C ; Levy, Finn Olav ; Bubb, Kristen J

Background and Purpose:

SER100 is a selective nociceptin (NOP) receptor agonist with sodium‐potassium‐sparing aquaretic and anti‐natriuretic activity. This study was designed to characterize the functional cardiovascular pharmacology of SER100 in vitro and in vivo, including experimental models of cardiovascular disease.

Experimental Approach:

Haemodynamic, ECG parameters and heart rate variability (HRV) were determined using radiotelemetry in healthy, conscious mice. The haemodynamic and vascular effects of SER100 were also evaluated in two models of cardiovascular disease, spontaneously hypertensive rats (SHR) and murine hypoxia‐induced pulmonary hypertension (PH). To elucidate mechanisms underlying the pharmacology of SER100, acute blood pressure recordings were performed in anaesthetized mice, and the reactivity of rodent aorta and mesenteric arteries in response to electrical‐ and agonist‐stimulation assessed.

Key Results:

SER100 caused NOP receptor‐dependent reductions in mean arterial blood pressure and heart rate that were independent of NO. The hypotensive and vasorelaxant actions of SER100 were potentiated in SHR compared with Wistar Kyoto. Moreover, SER100 reduced several indices of disease severity in experimental PH. Analysis of HRV indicated that SER100 decreased the low/high frequency ratio, an indicator of sympatho‐vagal balance, and in electrically stimulated mouse mesenteric arteries SER100 inhibited sympathetic‐induced contractions.

Conclusions and Implications:

SER100 exerts a chronic hypotensive and bradycardic effects in rodents, including models of systemic and pulmonary hypertension. SER100 produces its cardiovascular effects, at least in part, by inhibition of cardiac and vascular sympathetic activity. SER100 may represent a novel therapeutic candidate in systemic and pulmonary hypertension.

2001-07-01·The American journal of gastroenterology1区 · 医学

Effects of low doses of erythromycin on the 13C Spirulina platensis gastric emptying breath test and electrogastrogram: a controlled study in healthy volunteers

1区 · 医学

Article

作者: DiBaise, John K. ; Park, Faye L. ; Brand, Rhonda M. ; Brand, Randall E. ; Lyden, Elizabeth

OBJECTIVE:

Electrogastrography and stable isotope gastric emptying breath tests (GEBTs) are relatively simple, noninvasive tests of gastric motor function that may be useful in monitoring the effects of therapeutic interventions. It was our primary objective to examine the effects of low dose i.v. erythromycin on the results of the 13C Spirulina platensis GEBT and electrogastrography. We were also interested in evaluating the reproducibility of these tests.

METHODS:

In 10 healthy subjects (five female, ages 23-37 yr), we simultaneously performed the GEBT, using a prepackaged meal (340 kcal), and electrogastrography on each of four different occasions separated by at least 1 wk. After performance of baseline studies, they were repeated in random order after the infusion of 50 mg of erythromycin (Er50), 100 mg erythromycin (Er100), and a placebo (saline). Breath samples were obtained at baseline and at 75, 90, and 180 min after the meal and T1/2 and Tlag calculated. Electrogastrography recordings began 30 min before the test meal and continued for 2 h after the meal.

RESULTS:

Baseline and placebo T1/2 and Tlag were similar. Er50 resulted in a modest acceleration of gastric emptying (T1/2 Er50 vs baseline vs placebo = 104.0 vs 132.7 vs 125.5 min) and reduction in lag time (Tlag Er50 vs baseline vs placebo = 47.2 vs 61.5 vs 56.2 min). A similar decrease was seen in response to Er100. The baseline and placebo fasting and fed electrogastrography parameters were similar. After infusion of Er100, the percentage of normal slow waves in the first postprandial hour decreased relative to baseline and placebo (percent normogastria Er100 vs baseline vs placebo = 64.1+/-7.5 vs 82.4+/-6.4 vs 79.7+/-5.5). This corresponded with an increase in percent tachygastria during the same period and an overall decrease in the mean dominant frequency. Similar but less striking changes were seen after administration of Er50. Replicate GEBTs showed a high degree of reproducibility both within and between individuals for T1/2 and Tlag. In contrast, replicate electrogastrograms revealed moderate to high variability for all parameters except the dominant frequency.

CONCLUSION:

The stable isotope GEBT utilizing 13C S. platensis demonstrates responsiveness to the prokinetic effects of low dose i.v. erythromycin and good reproducibility.

项与 ER-100 相关的新闻（医药）

2024-10-21

·GlobeNewswire-Health Care

Life Biosciences Presents at AAO Highlighting Progress of Nonhuman Primate Studies Evaluating Partial Epigenetic Reprogramming to Restore Visual Function

Data replicate and expand upon the potential of ER-100 to improve retinal ganglion cell function and restore visual function in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (NAION)BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Life Biosciences (“Life Bio”), a biotechnology company advancing innovative cellular rejuvenation technologies to reverse diseases of aging and injury and ultimately restore health for patients, today announced new data presented at the 2024 American Association of Ophthalmology (AAO) Annual Meeting that took place in Chicago, Illinois from October 18-21, 2024. Results replicate previously reported nonhuman primate (NHP) data and further expand our knowledge on dosing and timing of treatment. ER-100, a novel partial epigenetic reprogramming gene therapy containing Oct-4, Sox-2 and Klf-4 (OSK), was administered via a single intravitreal injection along with daily systemic doxycycline to NHPs with a NAION-like injury. Immunohistochemistry confirmed expression of each transcription factor (Oct-4, Sox-2 and Klf-4) in discrete cells in the perifoveal regions in ER-100 treated NHPs relative to vehicle. Furthermore, ER-100 significantly reduced deficits in pattern electroretinogram and axon density measures when administered in both prevention and rescue paradigms. Collectively, these results demonstrate that ER-100 successfully targets retinal ganglion cells and reduces the loss of visual function in an NHP model of NAION. Life Bio remains on track to initiate the first human clinical study evaluating ER-100 for optic neuropathies in the second half of 2025. “Partial epigenetic reprogramming has the potential to restore visual function for those with optic neuropathies such as NAION and glaucoma,” said Sharon Rosenzweig-Lipson, Ph.D., Chief Scientific Officer of Life Bio. “The data shared today replicate and build upon our understanding of the dosing of ER-100 and the timing of the treatment window relative to the onset of NAION-related damage. We look forward to advancing this program toward human clinical trials next year for patients affected by these age-related optic neuropathies.” About Life Biosciences Life Biosciences is a biotechnology company advancing innovative cellular rejuvenation platforms to reverse diseases of aging and injury and ultimately restore health for patients. The company is focusing on two platforms targeting key mechanisms underlying aging biology, epigenetic reprogramming and chaperone-mediated autophagy, to restore cells to a more youthful state. Therapies developed within these platforms have the potential to prevent, treat, and/or reverse multiple aging-related diseases. For more information, please visit www.lifebiosciences.com or follow us on Twitter and LinkedIn. Media Contact Kristin Politi, Ph.D.LifeSci Communicationskpoliti@lifescicomms.com(646) 876-4783

细胞疗法基因疗法

2024-10-21

·BioSpace

Life Biosciences Presents at AAO Highlighting Progress of Nonhuman Primate Studies Evaluating Partial Epigenetic Reprogramming to Restore Visual Function

Data replicate and expand upon the potential of ER-100 to improve retinal ganglion cell function and restore visual function in a nonhuman primate model of nonarteritic anterior ischemic optic neuropathy (NAION) BOSTON, Oct. 21, 2024 (GLOBE NEWSWIRE) -- Life Biosciences (“Life Bio”), a biotechnology company advancing innovative cellular rejuvenation technologies to reverse diseases of aging and injury and ultimately restore health for patients, today announced new data presented at the 2024 American Association of Ophthalmology (AAO) Annual Meeting that took place in Chicago, Illinois from October 18-21, 2024. Results replicate previously reported nonhuman primate (NHP) data and further expand our knowledge on dosing and timing of treatment. ER-100, a novel partial epigenetic reprogramming gene therapy containing Oct-4, Sox-2 and Klf-4 (OSK), was administered via a single intravitreal injection along with daily systemic doxycycline to NHPs with a NAION-like injury. Immunohistochemistry confirmed expression of each transcription factor (Oct-4, Sox-2 and Klf-4) in discrete cells in the perifoveal regions in ER-100 treated NHPs relative to vehicle. Furthermore, ER-100 significantly reduced deficits in pattern electroretinogram and axon density measures when administered in both prevention and rescue paradigms. Collectively, these results demonstrate that ER-100 successfully targets retinal ganglion cells and reduces the loss of visual function in an NHP model of NAION. Life Bio remains on track to initiate the first human clinical study evaluating ER-100 for optic neuropathies in the second half of 2025. “Partial epigenetic reprogramming has the potential to restore visual function for those with optic neuropathies such as NAION and glaucoma,” said Sharon Rosenzweig-Lipson, Ph.D., Chief Scientific Officer of Life Bio. “The data shared today replicate and build upon our understanding of the dosing of ER-100 and the timing of the treatment window relative to the onset of NAION-related damage. We look forward to advancing this program toward human clinical trials next year for patients affected by these age-related optic neuropathies.” About Life Biosciences Life Biosciences is a biotechnology company advancing innovative cellular rejuvenation platforms to reverse diseases of aging and injury and ultimately restore health for patients. The company is focusing on two platforms targeting key mechanisms underlying aging biology, epigenetic reprogramming and chaperone-mediated autophagy, to restore cells to a more youthful state. Therapies developed within these platforms have the potential to prevent, treat, and/or reverse multiple aging-related diseases. For more information, please visit or follow us on Twitter and LinkedIn . Media Contact Kristin Politi, Ph.D. LifeSci Communications kpoliti@lifescicomms.com (646) 876-4783

细胞疗法基因疗法

100 项与 ER-100 相关的药物交易

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