See “MicroRNAs make big impression in disease after disease,” Science. 28 March 2008 and other papers in the Special Section on Gene Regulation
1. Preclinical trial - a laboratory test of a new drug or a new medical device , usually done on animal subjects, to see if that drug or device is safe to test on humans. Basic research is discovering facts by exploring, describing or explaining. Applied research is using the information from basic research to find treatments and preventions for illnesses. Answers will vary. Examples: Lung cancer, diabetes, heart disease….
This information is from the website: http://www.ppdi.com/about_ppd/drug_development.htm#2
In a biochemical pathway, each step usually involves either adding atoms (synthesis) or taking certain atoms away (degradation) to produce a different compound. These steps are often enabled by enzymes that are specific for that step. Drug development can be aimed at blocking or enhancing the enzyme or directly reacting the drug with the compounds in the pathway.
They really are the APPLIED steps of the scientific method. State the Problem: Will a new drug be effective and safe? Gather Background Information: The scientist will rely on past research and the basic research done before their proposed trial. Form a Hypothesis: For new drugs, the hypothesis is that the drug will be effective and safe, otherwise, the scientist would not spend the time and effort on the Pre-Clinical Trial. Conduct an Experiment: This involves screening the drug in the Bioassay. Analyze Data: Determining Safe and Toxic Doses and whether the drug was Effective. Forming a Conclusion: Will it be advantageous to continue testing the drug or not? Is it safe to continue on and test the drug on humans next? 2. Many times, the risks associated with using humans outweigh the potential benefits. Using a Bioassay like cells or fish embryos prevents unnecessary harm to people and pets. 3. Out of every 5,000 new compounds identified during the discovery process, only five are considered safe for testing in human volunteers after preclinical evaluations.
The Application of the Scientific Method: Preclinical Trials Copyright 2010. PEER.tamu.edu
What do you think? Have you ever had to take a medicine to treat an illness? Have you ever wondered how researchers determine if the medicines you take are safe or not?
Pre-Clinical Trials and Clinical Trials are the processes by which scientists test drugs and devices to see if they are SAFE and EFFECTIVE.
What is a Preclinical Trial? Preclinical trial - a laboratory test of a new drug or a new medical device, usually done on animal subjects, to see if the hoped-for treatment really works and if it is safe to test on humans.
There are two types of Research: Basic and AppliedBasic Research: discovering new facts about howthings work, how they are made, or what causes abiological event to occur. Basic research canexplore a topic, explain a topic or describe a topic.For Example: A researcher discovered that genescan be turned off or on by small RNA molecules inthe body. This study was conducted on worms. Itled to the Nobel Prize in 2006.
“Basic” vs. “Applied” ResearchApplied Research: Taking theinformation discovered in basicresearch and investigating how touse it to treat and preventsicknesses.Example: A researcher uses theinformation about turning genes Segment of DNA.off and on to find a drug that is Many such segments act asused to turn off genes that cause genes.diseases and disorders in humans.
Where Do We Get New Ideas For Research? Ideas come from all kinds of scientists and medicalprofessionals who do research in universities, government labs, and in corporations.
Take a Minute to Discuss: What is a Pre-Clinical Trial? What is the difference between basic research and applied research? What sickness or disease would you like to see an effective treatment for?
There are several steps involved with doing a Pre-Clinical Trial: File for approval as an Investigational New5 Drug (IND) 4 Establish Effective and Toxic Doses Screen the Drug in the Assay 3 Develop a Bioassay 2 Indentify a Drug Target 1
Steps in Doing a Pre-Clinical Trial:Step One: Get an idea for adrug target. Drugs usually act on either cellular or genetic chemicals in the body, known as targets, which are believed to be associated with disease. Scientists use a variety of techniques to identify and isolate individual targets to learn more about their functions and how they influence disease. Compounds are then identified that have various interactions with the drug targets that might be helpful in treatment of a specific disease.
Finding the Right Target Is Not Easy Parkinson’s Disease Example:Parkinsons disease:a disease which causesdeterioration of thecentral nervous systemover a period of time.This disease oftenimpairs the patient’smovement, speech, andother functions.
How is Parkinson’s treated? Where should the focus be? Tremors or shaking occurs when cells in one part of brain die. These cells communicate using a chemical called dopamine. Drugs that replace dopamine work only for a few years. Other Parkinson’s symptoms (depression, sleep disorder, digestive problems, loss of brain function) have other causes. Another sign of Parkinson’s disease: many cells have deposits of a protein, synuclein. Four drug companies are developing drugs to counter synuclein, even though nobody knows if it is a cause or a consequence of Parkinson’s. Synuclein could be like a tombstone—a marker, not a cause of cell death.
Drugs target specific points in biochemical pathways Biochemical pathways are series of chemical reactions occurring within a cell. In each pathway, a principal chemical is modified by chemical reactions. Examples of different types of biochemical pathways: A A B C D E E B Any step in the pathway, for example from A to B, or B to C, might be a target for the right D C drug. * See slide note
Steps in Doing a Pre-Clinical Trial:Step Two: Develop a BioassayA Bioassay is a “live” system that can beused to measure drug effect. It may be a culture of cells or organs or a whole animal.For example: Zebra-fish embryos - you can see effects of drugs on bone density, blood vessel growth and many other systems of the zebra-fish.
Steps in Doing a Pre-Clinical Trial:Step Three: Screen thedrug in the Bioassay. This is the actual test of the drug on the chosen bioassay. This will determine if the drug is SAFE and if it is EFFECTIVE in the bioassay (BEFORE it is ever tested on humans!)
Steps in Doing a Pre-Clinical Trial:Step Four: Establish what dosageamount of the drug is safe and whatdosage amount of the drug is toxic. Most drugs have a toxic level or an amount at which the drug will become harmful instead of helpful.
Steps in Doing a Pre-Clinical Trial:Step Five: Application is made to theFood and Drug Administration (FDA)as an Investigational New Drug (IND). IND must show how the drug: Is manufactured. Appears (color, solubility, melting point, particle size, moisture content). Formulated (pills, liquid, etc. + inactive ingredients). Will be analyzed for purity, concentration, stability. Will be tested for safety (this will be the basis for allowing first use in humans).
Think Break: How are these steps like the steps of the Scientific Method? Why would research scientists use a Bioassay instead of a human subject to test a new drug? What percentage of drugs do you think get this far in the process?
Review: Steps to New Drug Discovery Pre-Clinical Trials Get idea for drug target Develop a bioassay Screen chemical compounds in assay Establish effective and toxic amounts File for approval as an Investigational New Drug (IND) (leads to clinical trials)
Can you summarize the process?With a partner or your group, write a summary ofthe Pre-Clinical Trial Process. Use the followingwords to help you: Drug Safe Effective Basic Research Applied Research Target Biochemical Pathway Bioassay Toxic Investigational New Drug (IND)
Pre-clinical Research at Texas A&MCollege of Veterinary Medicine andBiomedical Sciences