Mitochondrial toxicity test

A technology of mitochondria and mitochondrial complexes, applied in the detection of programmed cell death, biological testing, measurement devices, etc., can solve problems that are difficult to translate into human applications, and achieve the effect of reducing time and cost and avoiding pain

Inactive Publication Date: 2015-06-10
NEUROVIVE PHARMA AB
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  • Abstract
  • Description
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Problems solved by technology

[0004] Mitochondrial toxicity of drug candidates is currently mostly evaluated in animals and cell cultures, with results difficult to translate to future human applications

Method used

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Experimental program
Comparison scheme
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Embodiment Construction

[0150] Experimental part

[0151] Materials and methods

[0152] 1.1 Obtaining human samples

[0153] This study was approved by the regional ethical review board of the Rand region in Sweden (adults: 113 / 2008 and 644 / 2009, children: 59 / 2009) and the ethics committee of Tokyo Medical University in Japan (permission No. 1514) approval. For adults in Sweden, from Landskåne University Hospital ( The Blood Donation Center at the University Hospital collects blood samples from healthy donors, as well as from healthy adults recovering from knee injuries. The Japanese group consisted of healthy adult volunteers. Samples were obtained after obtaining written informed consent. Trials were conducted according to the same procedures and protocols and by the same investigators at both research stations. Pediatric control samples were obtained from patients undergoing minor elective surgery. Written informed consent was obtained from parents or guardians, and blood was drawn before...

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Abstract

A novel method useful in drug screening. The method is useful for testing effects of substances on the mitochondria, notably toxic or beneficial effects of drug substances or candidate drug substances. The method is based on measurement in live human mitochondria ex vivo, but in a setting as near the in vivo situation as possible. The method is also useful for testing substances impact on the mitochondrial respiration. The method can be used to i) screening and selection of early or late stage drug candidates in cells derived from blood from healthy individuals or in so-called buffy coat, which is a concentrated solution of platelets and white blood cells, ii) testing a patient's sensitivity to a known mitochondrial toxicant, iii) analysing mitochondrial drug toxicity in clinical trials, and / or iv) analysing beneficial effects of drugs intended to improve mitochondrial function

Description

technical field [0001] The present invention provides new methods for drug screening. In particular, the method is useful for detecting the effects of substances on mitochondria, especially toxic or beneficial effects of drug substances or candidate drug substances. The method is based on measurements in living human mitochondria in vitro, but in an environment as close as possible to the in vivo state. The method can also be used to examine the effects of substances on mitochondrial respiration. Background technique [0002] In drug development, it is difficult to estimate whether a drug will affect energy-producing mitochondria when used in humans. Many new drugs approved by the FDA in recent years have subsequently been withdrawn due to effects such as cardio or hepatotoxicity. Thus, of the new drugs registered by the FDA between 1994 and 2006, 38 were withdrawn due to toxic effects on the liver and heart, typical symptoms of mitochondrial toxicity. Apparently, these ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N33/50
CPCG01N33/5079G01N33/5094G01N2500/00G01N2500/10
Inventor 弗雷德里克·舍瓦尔约翰内斯·埃英格芒努斯·汉森埃斯基尔·埃尔梅尔德里克·格雷戈里·巴彻勒
Owner NEUROVIVE PHARMA AB
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