In 2008, the CMTA’s Board of Directors launched its Strategy to Accelerate Research, or STAR. It was based on two important ideas:
Idea #1: The Genes That Cause CMT Are Known.
We know the causes of many types of CMT. The big breakthrough came in 1991 when PMP22, the gene that causes CMT1A, was discovered. Today 90 different genes that cause CMT have been identified and more are being discovered each year. Once we identify a gene that causes CMT, we can duplicate it in the laboratory. This is the foundation of the STAR strategy. As a famous inventor put it: “A problem that is well stated is half resolved.” This is true of CMT, unlike many other diseases whose causes are either unknown or very complex.
Idea #2: Manage Research According to Sound Business Principles.
STAR is based on five core business principles:
- Develop a strategy based on knowing the cause of the disease and where to focus.
- Find the best researchers in the world and ask them to implement projects that support the strategy.
- Create accountability – Hold those researchers accountable for achieving their goals. We take your money very seriously. Our researchers are not fully paid until they fully deliver.
- Demand collaboration – We bring the researchers out of their silos to collaborate with each other. We are now seeing more and more technologies and therapies emanating from many different fields of study.
- Encourage partnerships – It costs between $400 million and $1 billion to bring a new drug to market. The CMTA does not have this kind of money. We have to work with big, strong pharmaceutical companies that have the money to develop drugs. In the end, they will carry the ball over the line for us.
Our strategy has five key elements:
- Assays – Assays are tests. We recreate CMT in Petri dishes and then use high-throughput screening (HTS) to test hundreds of thousands of drugs to see if they affect it. We are looking for hits—drugs that correct the defect of a particular type of CMT.
- Animal Models – We take the promising hits and test them on laboratory animals, narrowing the millions of potential compounds down to a few of the most promising.
- Stem Cells – We take human skin samples and put them through a stem cell process to create neurons (nerve cells) and Schwann cells (which make myelin). This way, we create assays that better represent human biology. We have developed models for CMT1A and CMT Type 2.
- Partners – We’ve tested millions of compounds to see if they affect CMT1A. With the help of a major pharmaceutical company, we’ve found several promising ones that need to be fine-tuned for humans. We’ve created a “toolbox” with the assays, animals and tests so that companies with new therapies for CMT can work with us to test them. This includes new technologies from other domains. We can get solutions from the entire medical field. For example, four different drug companies that work on many different diseases recently reached out to the CMTA to discuss potential therapies.
- Clinical Trials – We are working to get ready to conduct clinical trials, including developing outcome measures, which measure a drug’s effectiveness against CMT.
We created an advisory board with top-notch researchers. The Scientific Advisory Board has 14 world-class scientists. Because the work of STAR involves translational research—turning science into therapies—we created a Therapy Expert Board (TEB)–a group of experts who tell us how good the science is in terms of turning it into therapies for those with CMT.
More recently, we realized we had to get ready for clinical trials so we created the Clinical Expert Board (CEB), a group of experts who are helping us and our partners think about how to design clinical trials.
The Scientific Advisory Board (SAB)
Provides scientific input for projects that are ongoing or proposed (14 members)
John Svaren, PhD, Chair
University of Wisconsin
The Therapy Expert Board (TEB)
Ensures that each research project has translational value (6 members)
Mark Scheideler, PhD, Chair
HumanFirst Therapeutics LLC
The Clinical Expert Board (CEB)
Provides expert guidance and support to the CMTA’s alliance partners to assure the success of clinical trials (8 members)
Michael E. Shy, MD, Chair
University of Iowa
We have come a long way since the inception of STAR in 2008. Over the last two years, the CMTA has financed 40 projects and spent $3.5 million on research. We are spending your dollars wisely and in a very focused manner. We are spending 10 times more on research than when we initially started. Thanks to the support from all our donors, there is huge momentum and promise.
CMTA Research Updates by Disease:
Over the past eight years, we’ve done animal studies, performed HTS, identified hits and worked with a company called Genzyme. Today, we’re focused on two families of compounds that are being fine-tuned in the lab. Genzyme, a traditional pharmaceutical company, takes a small molecule approach, which utilizes chemical formulas. In parallel, we are also working with biotech companies, which create biological living proteins, or large molecules. For example, a company came to us with a very interesting approach—RNA interference—which inserts little pieces of DNA into nerves to affect the way the cells create the protein that overexpresses PMP22. We’ve seen promising results in rat testing. This technology is currently used in two approved drugs on the market.
CMT1X is the second most common type of CMT. Researchers have identified a relationship between CMT1X and inflammation. We’ve identified the source of this inflammation and we are going after therapies to target this source. The approach comes from cancer research. Another approach is gene therapy, meaning that a virus sends DNA to the nerves that replaces the defective gene. We are also investigating gene therapy for CMT4.
We have good assays and mouse models. We’ve also had several hits and potential compounds. As in CMT1X, inflammation may play a role in CMT1B, so CMT 1X research might help CMT1B.
We’ve patented a rat model and have seen promising results using stem cells. We will also complete a small screening of FDA-approved drugs this year.
We have stem cell assays and good animal models. Testing will commence soon.
Clinical Trials – How You Can Help
Everyone with CMT has an important role to play. There are currently 20 Centers of Excellence in the United States and abroad. Clinicians need as much data on as many patients as possible to help drug companies conduct successful trials. You can help by joining our Patient Registry. We are also developing “outcome measures” to see if drugs are effective as soon as possible so that we can keep the trials short and inexpensive. The traditional CMT test scores require too much time to show if a drug is working or not, so we are looking at various “biomarkers” such as fat content in calf muscles or certain chemicals in the blood.
To participate in CMT research studies, please join the Patient Registry. You do NOT need to know the exact type of CMT you have to join this registry. And everyone in the world who has CMT can join!