New type of laboratory mice may be key to individualizing cancer treatment for sensitive individuals
Laboratories performing toxicity testing on chemotherapy drugs often find that, for some individuals, the treatment is as detrimental to health as the cancer itself. "Adverse drug reactions can be difficult to study in humans," Jackson Laboratory scientist Dr. Gary Churchill says. "Every individual is genetically unique and lives in an uncontrolled environment. That's why we need animal model systems to fully understand the genetic basis of drug response.”
To better model human populations, Dr. Churchill co-designed a new strain of laboratory mice called Diversity Outbred or DO mice. These mice are quite different from the inbred or hybrid strains usually used in drug toxicity testing because each DO mouse has a unique genetic profile. The DNA of DO mice colonies display normal levels of heterozygosity, which approximates the genetic diversity in the human population better than the inbred varieties.
“Testing chemo drugs in DO mice will be almost like testing them in every person on Earth. This sets the scene for future, highly reliable screens for cancer patients," Dr. Churchill reports. This new approach may prove to be invaluable in improving therapy for individuals who are unable to tolerate a cancer-killing or other type of drug.
Best-in-Class Toxicology Testing:
- Use healthy animals, which have not been previously involved in experiments and have had at least a 7-day acclimation period to laboratory conditions
- Test protocol utilizes three or more dose levels and a control
- Make sure that the highest dose level is enough to identify the toxic effects while avoiding severe toxicity, suffering or death
Top Considerations Before Selecting Toxicology Testing:
Much controversy surrounds animal testing, not only because of the suffering inflicted on the animals. A number of scientists argue that progress is held back by using animal models, which they claim cannot reliably predict effects in humans. The three “R’s”: replacement, reduction and refinement, are principles adopted by many countries. “Replacement” options include in vitro cell culture techniques, in silico computer simulation, the use of humans for skin irritancy tests, donated human blood for pyrogenicity studies and microdosing, in which human volunteers receive doses well below those expected to produce whole-body effects. Investigating whether one of these methods represents a suitable alternative may end up yielding better results at a low cost.
Key Producers:
1. Rules-Based Medicine’s (RBM) Rat & Human KidneyMAP panels provide sensitive detection and quantitation of kidney damage caused by drug-induced renal toxicity, which is a leading cause of failure in drug development programs. These panels have the degree of sensitivity required to identify kidney damage before it becomes permanent. RBM reports that “Our proprietary Multi-Analyte Profiling (MAP) platform makes the drug discovery & development process more efficient and effective by providing pre-clinical and clinical researchers with reproducible, quantitative, multiplexed immunoassay data.” Corporate headquarters and CLIA-certified biomarker testing laboratory are in Austin, TX; multiplex assay development and manufacturing is in Lake Placid, NY and a subsidiary unit is located in Germany.
2. BIOCIUS Life Sciences, Inc.'s management team has extensive experience with toxicity testing. CEO Dr. Can C. Özbalis, who is responsible for much of the RapidFire® Lead Discovery development, earned a Ph.D. in Toxicology from Massachusetts Institute of Technology. RapidFire technology enables the screening of targets that are not amenable to fluorescence or luminescence. Biocius says that “RapidFire MS is 10 to 100 times faster than conventional MS screening methods.” This technology can either be used by the customer or provided as a contract research service. This privately held company is based in Wakefield MA and has a sales office in Switzerland.
3. The Jackson Laboratory offers state-of-the-art facilities, research support and a wide range of technologies, as well as mice colonies, to organizations around the world engaged in toxicity testing. This company, which was started in 1929 as one of the first centers for cancer genetics research, is a major provider of genetic resources, software, and expertise to the scientific community. This independent, non-profit laboratory has two facilities in Maine and California and plans for a third in Florida, which will be funded by the state. The Jackson Laboratory also advances science by offering academic programs for teachers and students as well as for corporate researchers.
4. Geneva Laboratories, Inc. offers laboratory services, including toxicology testing, to the pharmaceutical and other industries. Geneva Labs has a 22,000 sq. ft. complex containing testing laboratories for Chemistry analysis, Microbiology and Biocompatibility, including six ISO Class 5 (Class 100) clean rooms as well as a 21,000 sq. ft. facility for special projects and stability studies. Geneva Laboratories is FDA registered, GLP compliant and certified to ISO 9001 and ISO 17025 standards. This company was started in 1976 and is headquartered in Elkhorn Wisconsin.
Toxicology Testing
Definition: Toxicity or toxicology testing, also known as safety testing, refers to the procedures used to determine whether drugs or other household products have adverse affects on living organisms.
