Netrin-1 Compounds as Post-MI and Post-Angioplasty Therapeutics as well as for Treating Renal and CNS Reperfusion Injury
- 技術優勢
- All three peptides are small (9-11 amino acids in length) – enabling scalability in production More affordable than full-length netrin-1 peptide Pharmacologically feasible in production, storage and application
- 技術應用
- Based on the mechanisms of action for these lead compounds, there are at least three different therapeutic concepts for this: (1) acute therapy for treatment of reperfusion injury (post-MI, renal reperfusion injury and stroke), (2) chronic therapy for the prevention of post-MI remodeling and fibrosis to prevent heart failure and (3) post-angioplasty therapeutic to prevent restenosis.
- 詳細技術說明
- UCLA researchers in the Department of Anesthesiology have identified three novel short netrin-1 derived peptides for the improved treatment of MI. The present technology exerts cardioprotection by exploiting the netrin-1 pathway through binding to its receptor DCC to increase the production of nitric oxide. Treatment of the netrin-1 derivatives in freshly isolated ischemic reperfused hearts reduced infarct size – indicating significant reduction in myocardial injury. The present technology provides three superior short netrin-1 derived peptides for the treatment of MI with improved scalability and fewer adverse side effects. Different combination recipes using the three peptides are additionally beneficial.
- *Abstract
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UCLA researchers have invented a method of decreasing myocardial injury and infarct size through the intravenous administration of the netrin-1 or netrin-1-derived peptides during a cardiac event. These agents have powerful cardioprotective effects and provide a novel and effective therapy for the treatment of myocardial infarction.
- *IP Issue Date
- Jul 27, 2017
- *Principal Investigation
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Name: Hua Linda Cai
Department:
Name: Qiang Li
Department:
- 申請號碼
- 20170210780
- 其他
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State Of Development
Ex vivo delivery of the present technology to the heart induced cardioprotection via DCC-dependent activation of ERK1/2 and eNOS. Background
Netrin-1 is a novel endothelial mitogen that stimulates production of nitric oxide (NO•) which has a well-established role in cardioprotection. In order to develop a viable netrin-1 therapeutic a team at UCLA has developed and optimized a series of novel short peptide derivatives of netrin-1 ranging in length from nine to eleven residues. The compounds have been validated in vivo in rodents, and porcine studies are underway.
These lead compounds function at three different mechanistic levels which may lead to three distinct cardiovascular therapeutic product concepts as well as therapeutics for renal reperfusion injury and stroke.
1. Prevention of reperfusion injury: The first level is acute protection to reduce post-MI infarct size more than 50% when given immediately at the onset of reperfusion or pre-reperfusion. The mechanisms involved include receptor DCC dependent ERK1/2/eNOS phosphorylation and NO• production to directly protect cardiomyocytes against injury. This mechanism may present therapeutic opportunities in renal reperfusion injury and stroke.
2. Prevention of post-MI remodeling and fibrosis: The second level is inhibition of oxidative stress and autophagy. This may lead to a chronic therapy to prevent post-MI remodeling and fibrosis of the heart and thereby sustain cardiac function and prevent development of post-MI heart failure.
3. Prevention of restenosis: The third level is inhibition of restenosis/re-occlusions of coronary arteries post angioplasty.In animal models this has been shown to be 100% effective.
Related Materials
Netrin-1 prevents ischemia/reperfusion-induced myocardial infarction via a DCC/ERK1/2/eNOS s1177/NO/DCC feed-forward mechanism.
Pharmacological postconditioning treatment of myocardial infarction with netrin-1.
Netrin-1 improves post-injury cardiac function in vivo via DCC/NO-dependent preservation of mitochondrial integrity, while attenuating autophagy.
Netrin-1 abrogates ischemia/reperfusion-induced cardiac mitochondrial dysfunction via nitric oxide-dependent attenuation of NOX4 activation and recoupling of NOS.
Central role of SIAH inhibition in DCC-dependent cardioprotection provoked by netrin-1/NO.Additional Technologies by these Inventors
- Growth Factor Treatment of Myocardial Infarction
- A Novel Biomarker for Abdominal Aortic Aneurysm
- Circulating Biomarker for Early Detection of Post-Operative Cardiac Arrhythmias
Tech ID/UC Case
24830/2014-526-0
Related Cases
2014-526-0
- 國家/地區
- 美國
