 In the May/June 2009 issue of The CMTA Report, we announced the completion of Phase 1 of the STAR program. A CMT1A cell line, created by Dr. Ueli Suter in Zurich, Switzerland, has been sent to the NIH Chemical Genomics Center (NCGC) in Rockville, MD, where it has been undergoing a necessary period of growth in preparation for high-throughput screening (HTS).
This month, we are pleased to announce the appointment of Sung-Wook Jang to a three-year term as a CMTA post-doctoral fellow at the NCGC. Sung-Wook, who has a PhD in Cellular and Molecular Biology from the University of Wisconsin in Madison, will work closely with scientists at the NCGC and be responsible for the development and performance of screening efforts using the NIH compound library to find therapies for Charcot-Marie-Tooth inherited peripheral neuropathy.
 | A Kalypsys robot at the NCGC holds a
1536-well plate similar to those that will be
used during the high-throughput screening
(HTS) of the CMT1A cell line. |
Sung-Wook’s initial work, scheduled to begin later this month, will involve conducting biological assays using the CMT1A cell line. (A biological assay, or bioassay, is a test performed to measure the effect of a substance on living matter, e.g., the CMT1A cells.) What’s remarkable about high-throughput screening is that it will enable Sung-Wook and his NCGC colleagues to conduct bioassays using the more than 350,000 drugs and other compounds in the NIH chemical library as reagents.
And we don’t know yet how many promising compounds will be identified, but it’s vitally important that we have a way of determining which of those compounds are likely candidates for further testing.
This is one key reason the CMTA chose to do the HTS at the NIH. Over the next several months, Sung-Wook and the NCGC scientists will perform sophisticated informatics analyses within and among screens and use other advanced techniques to optimize their understanding of the activities of these compounds in biological systems.  | The NCGC Chemical Library:
Some of the 350,000 compounds stored here
may become treatments for CMT. |
It’s also why the CMTA initiated work on two other crucial projects in the STAR program. One, currently being undertaken by Klaus Nave at the Max Planck Institute for Experimental Medicine in Gottingen, Germany, is focused on developing a laboratory model of the disease because we need to know if the effects we observe in HTS will also be observable in animals.
The other, being pursued by John Svaren in his lab at the University of Wisconsin at Madison, where Sung-Wook also studied, is designed to further our understanding of how PMP22 is expressed and regulated and tell us whether the same constructs will be observed in humans.
These two studies will ultimately help us determine which compounds will be the best candidates for laboratory and clinical trials, and the fact that we have already begun these projects has allowed us to not only increase our chances of success, but also to significantly shorten the time involved in the drug development process.
We’re projecting that it will take between three and five years to develop a treatment for CMT1A, when, on average, it takes two to four years of work and $10 million to move a drug through the preclinical process alone. Then it can take years and millions more to bring it to the marketplace. With the risk involved, it’s no wonder pharmaceutical companies seldom get involved in the development of drugs for rare or orphan diseases like CMT that affect fewer than 200,000 people in the United States.
That means that while STAR has enabled us to advance the timetable, you and the CMTA have had to fund the research. We expect that we will benefit from that in the long run, especially when it comes to funding research for other forms of CMT, but we are also optimistic that a new program announced by the NIH will greatly increase our ability to develop therapies for CMT.
It’s called the Therapeutics for Rare and Neglected Disease program, or TRND, and, according to Christopher Austin, the director of the NCGC, one goal of the program is to “de-risk” drug development projects sufficiently in the preclinical phase to make them adoptable by private industry.
TRND will work closely with disease-specific experts, using in-house scientific capabilities to carry out much of the development work, and it will also work to find a company willing to help carry out clinical trials if a drug successfully passes the preclinical phase. (For more on TRND, visit www.nih.gov/news/health/may2009/nhgri-20.htm.
Although the CMTA began work on STAR well before the announcement of TRND and built a solid foundation for successfully identifying and shepherding a potential treatment for CMT1A through the preclinical process, we are still in an excellent position to benefit from a program like TRND as we begin the HTS phase of our preclinical work.
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