MIND Drug Screening Laboratory
Given the dramatic advances in treating other diseases such as cancer and heart disease, why are there no therapies that can halt brain cell death? Economic factors have played a significant part: licensing and marketing issues have created disincentives for pharmaceutical firms to enter on the ground floor of costly drug development for diseases that have long been considered incurable. In response, MIND and its dedicated Drug Screening Laboratory were created to bypass economic obstacles and hasten the early stages of drug discovery. Their “nonprofit biotech” approach joins academic investigators and experts in drug discovery to methodically seek agents with the power to disrupt and negate disease mechanisms.
The high-throughput Drug Screening Laboratory at MIND is under the direction of Anne B. Young, MD PhD and supervised by Alex Kazantsev, PhD. Dr. Kazantsev is a molecular biologist who has specialized in understanding neurodegenerative disease at the cellular level and has designed assays and screened compounds for potential therapeutic use in neurodegenerative disease.
The drug screening laboratory is an integral component of MIND’s structure that is designed to help translate basic science into leads for treatment. Dr. Kazantsev works with each lab in MIND to develop new projects in collaboration with the scientists. Currently, he has thirteen separate project in various stages of development to screen compounds for Huntington’s Disease, ALS, Parkinson’s and Alzheimer’s disease. The laboratory provides the personnel, resources, and expertise to make this transition. This process comprises three phases:
Assay Development — Converting a novel scientific idea into a drug screening project typically takes twelve months or more of development time. First, a miniature, cell-based model of the disease is created in the laboratory and then modified to enable testing in an automated laboratory. The science of modifying an assay for high throughput screening is an art in itself and usually involves adjusting it for maximum sensitivity and reliability. In addition, an ideal assay is one that can be easily standardized, miniaturized and adapted for execution by robotics in order to allow the measurement of different drug interactions that can slow disease in a test tube.
Drug Screening and Secondary Testing — Once an assay is created and refined, the lab’s robotic screening equipment (technology not typically found in an academic setting) tests MIND’s library of 30,000 drug-like compounds to determine which appear effective in combating the disease. “Hits” that are identified in the high-throughput laboratory then need to be verified in secondary assays which are done manually in several investigators’ laboratories. The most promising compounds then may be chemically altered and retested to see if slight changes in the molecules produce more powerful effects or better attributes for animal testing.
Preclinical Testing — Potential drug candidates for the various neurodegenerative diseases must undergo further testing in cells, fruit flies and mice before they are ready to be tested in humans. Animal models of PD, HD, ALS, AD, and other neurodegenerative diseases allow researchers to constantly screen many potential therapies before they reach the human trial stage. By rejecting those that are ineffective in animal models, the number of drugs that make their way to costly late-stage human testing is reduced. As a result, drug testing is streamlined and the overall costs of bringing promising new drugs to patients are controlled. Extensive experimentation is needed to determine the most effective methods of administration, dosing levels and length of treatment. This requires several separate trials to be run simultaneously to expedite the discovery process.
MassGeneral Institute for Neurodegenerative Disease
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