Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Methods and platforms for drug discovery

A technology of cells and health conditions, applied in biochemical equipment and methods, testing pharmaceutical preparations, animal cells, etc., can solve problems such as side effects, and no evaluation of the effectiveness and toxicity of candidate drugs

Inactive Publication Date: 2011-09-28
KYOTO UNIV
View PDF49 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

A major shortcoming in most current drug development attempts is that they do not assess the efficacy and toxicity of drug candidates in the context of the extreme genetic diversity of human patient populations
Indeed, even with experimental success in relatively small human clinical trial populations, these drugs can have unanticipated side effects once they are administered to a broader human patient population

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Methods and platforms for drug discovery
  • Methods and platforms for drug discovery
  • Methods and platforms for drug discovery

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0259] Example 1. Generation of iPSC lines from patients with spinal muscular atrophy

[0260] Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by degeneration of motor neurons and is one of the leading causes of paralysis and death in children. The disease shows a wide range of severity affecting infants to adults and is divided into types I-IV based on age of onset and severity of symptoms: type I "infantile", onset at 0-6 months of age and generally fatal ; Type II "intermediate type", onset at the age of 7-15 months, unable to stand or walk, but has partial ability to maintain a sitting position; type III "juvenile type", onset at the age of 19 months to 17 years, with walking Partial ability, although possibly temporary; Type IV "adult form", with some muscular strength, but the genetic basis of which is unknown.

[0261] The molecular basis of SMA is associated with the motor neuron survival (Survival Motor Neuron, SMN) gene. The region of chrom...

Embodiment 2

[0266] Example 2. Identification of motor neurons that improve classification in patients with spinal muscular atrophy Analysis of sub- and cellular disease phenotypes

[0267] We sought to identify increased SMN2 in motor neurons derived from patients with SMA E7 Transcript level molecules. In principle, by promoting the transcription of SMN2, reducing the degradation of SMN2 mRNA or increasing splicing into SMN2 E7 SMN2 pre-mRNA fraction of mRNA to increase SMN2 E7 Transcript levels. SMA patient-specific motoneurons were obtained by first generating panels of iPS cell lines from Type I, Type II, and Type III SMA patients as described in Example 1, and then differentiating the iPSCs into motoneurons. Establishment of an SMA patient SMN2 minigene reporter iPSC line for easy readout of SMN2 in motor neurons prior to motor neuron differentiation E7 Transcript levels.

[0268] After obtaining parental informed consent, from about 30 type I, 30 type II and 30 type III SMA...

Embodiment 3

[0275] Example 3. From genes associated with idiopathic Parkinson's disease and Parkinson's disease Generation of iPSC lines from patients with defined mutations iPSC

[0276] Parkinson's disease (PD) is one of the most common neurodegenerative diseases of old age, affecting 1-2% of the population over 65 years of age. Clinical signs include: rest tremor, bradykinesia, and rigidity. We hope to generate iPSC models of PD patients to identify candidate therapeutic agents that can slow, halt or reverse PD progression.

[0277] From 10 healthy control subjects with no known PD family history, 10 patients with sporadic PD (patients each have a protein encoding α-synuclein (PARK1), parkin (PARK2), PINK1 ( Mutations in the PARK6) or LRRK2 (PARK8) genes, a total of 10 patients for each mutation) generated iPSC lines from skin biopsies. iPSCs were generated as described in Example 1. Then, dopaminergic neurons were generated by differentiating each patient iPSC line and control ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention involves methods for identifying an agent that corrects a phenotype associated with a health condition or a predisposition for a health condition. The invention also involves methods for identifying a diagnostic cellular phenotype, determining the risk of a health condition in a subject, methods for reducing the risk of drug toxicity in a human subject, and methods for identifying a candidate gene that contributes to a human disease. The invention also discloses human induced pluripotent stem cell lines.

Description

Background technique [0001] The pharmaceutical industry has expended enormous technical and financial resources to develop new therapeutic agents. However, the failure rate (greater than 90%) of the lead compounds remained persistently high. Often lead drug compounds that meet expectations in preclinical models (eg, inbred animal models or small cell lines) are toxic or ineffective when administered to human clinical trial patient populations. A major shortcoming in most current drug development attempts is that they do not assess the efficacy and toxicity of drug candidates in the context of the extreme genetic diversity of human patient populations. In other words, in the current drug development paradigm, the effectiveness and toxicity of drugs are not tested in many, if not most, of the relevant genotype / phenotype combinations that exist in the human population. In fact, even when trials are successful in relatively small human clinical trial populations, these drugs may...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): C12Q1/02C12N5/071G01N33/15
CPCG01N33/5073
Inventor 樱田一洋K·J·希登曼
Owner KYOTO UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com