Research and Drug Development for Huntington's Disease
Drug Development/ Pre-Clinical Animal Studies
Once a lead compound is identified, it must be tested for toxicity in animals. Scientists are usually required to test the lead compound in two types of animals, typically a rodent and a larger animal. It is important to note animal models are not used in these tests for toxicity, meaning that they do not have the relevant disease condition. While animal models are often used in basic research and in target identification, healthy animals are used in these studies so scientists can determine the baseline levels of toxicity. Researchers test many dosage variables of the compound by administering various concentrations to the animals, changing how often the drug is given (frequency), and how long the drug is administered for. The drug can be administered in a chronic regimen, meaning it is administered frequently to keep the concentration at a constant rate. Alternatively, it can be administered in an acute regimen, meaning that it is given in an initial high dose and then is eliminated from the body.
Essentially, these studies are looking for the best treatment regimen with the least amount of toxic side effects. This is the therapeutic window, the dosage range in which the benefit of the drug outweighs its toxic effect. Throughout drug development and animal testing, researchers are also investigating the pharmacokinetics and pharmacodynamics of the lead compound.
Pharmacokinetics essentially looks at what the body does to the drug, and usually is characterized by the ADME, or absorption, distribution, metabolism, and excretion of the compound. Pharmacodynamics looks at what the drug does to the body. This looks at the dose-response relationship, and what effect the drug has on each of the major organs within the animal. It looks for any evidence that the drug is mutagenic (causes DNA mutations), carcinogenic (causes cancer), or teratogenic (causes problems with fetal development). Researchers also look for any long term or delayed effects in the animals.
HD and Pre-Clinical Development
There is a good deal of research in the HD community devoted to drug development, although more biological targets are needed for the field to grow much more. Among its many activities in drug discovery and development, CHDI, Inc has recently contracted with Edison Pharmaceuticals, Inc to develop new formulations of Coenzyme-Q10 that will act as more targeted forms. For more information on Coenzyme-Q10, click here.
VistaGen Therapeutics, Inc., a pharmaceutical company devoted to the discovery and development of small molecule therapies using stem cell technology has recently been awarded a grant from the NIH to do pre-clinical development of AV-101. This is a drug candidate with the potential to reduce the production of quinolinic acid, a neurotoxin produced in the brain that is believed to be involved in HD.
Last Modified: 05/22/2009
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