CMTA: Turning Science into Therapies
On Saturday, March 18, the CMTA put on a Patient/ Family Conference in collaboration with the University of Miami. We had a wonderful turnout, with people from all over the world in attendance. Gilles Bouchard, the CMTA’s Board Chair, explained progress to date on CMTA-funded research. I wanted to share my notes with You!
In 2008, the CMTA’s Board of Directors launched STAR, or Strategy to Accelerate Research. It was based on two important ideas:
Idea #1: Causes Are Known
We know the causes of many types of CMT. The big breakthrough was in 1991 when the gene PMP22 for CMT1A was discovered. Today 90 different genes have been identified as causing CMT and more and more types of CMT are being discovered each year. This is the foundation of the STAR strategy because if we know the cause of the disease, we can duplicate it in the laboratory. It is often said that “a problem that is well stated is half resolved,” and this is the case for CMT, unlike most other diseases where causes are either unknown or very complex.
Idea #2: Manage Research According to Sound Business Principles.
STAR is based on 5 core business principles:
- a) Strategy: based on knowing the cause of the disease and what to focus on.
- b) Our team finds the best researchers in the world and asks them to implement the projects to support our strategy, unlike most foundations who fund the best projects which are presented to them.
- c) Accountability is not the most prevalent value in the world of research. We hold our researchers to their goals. We take your money very seriously. Our researchers are not fully paid until they fully deliver.
- d) Collaboration: researchers still tend to work in silos. They are experts in one domain and have one focus. To solve CMT, we bring people from different fields together so that they work collaboratively. We are now seeing more and more technologies and therapies emanating from many different fields of study.
- e) Partnerships: developing a new drug is not inexpensive. It costs between 400 million to 1 billion dollars to bring a new drug to market. The CMTA does not have this kind of money. We have to work with those who have the money to develop the drugs – big, strong pharmaceutical companies. In the end, they will carry the ball over the line for us.
Our Strategy. There are 5 keys elements to our strategy:
1) Assays. Assays are tests. We recreate CMT in Petri dishes. And then with high throughput screening or HTS, we test hundreds of thousands of drugs. This gives us a way to see if the medications tested have any effect on CMT. We are looking for hits. What are hits? Hits are drugs that have a positive effect on CMT.
2) Animal Models. Once we have promising hits, we then test them on laboratory animals. From millions of potential compounds, we can narrow it down to a few of the most promising compounds or drugs.
3) Stem Cells: We take human skin samples and put them through a stem cell process to create Neurons (nerve cells) or Schwann cells (which make myelin). This way, we create assays that better represent human biology. We have good models for CMT1A and have been successful with CMT type 2.
4) Partners: For CMT1A, we’ve tested millions of compounds and with the help of a major pharmaceutical company; we have several promising compounds which need to be fine-tuned for humans. With the assays, animals, and tests, we’ve created a “toolbox” for anyone who has new therapies for CMT. They can come and work with us and test them, including new technologies that may be from other domains. We can get solutions from the entire medical field. For example, 4 different drug companies who work on many different diseases reached out to the CMTA in the past couple of months alone to discuss potential therapies.
5) Clinical Trials: We are working to get ready to conduct clinical trials and develop outcome measures – how do we measure whether a drug is effective for CMT or not? See further for more details
How do we work?
We created an advisory board with top-notch researchers. The Scientific Advisory Board has 14 world class scientists. The work of STAR is not only about science, but about turning science into therapies. Another way of saying turning science into therapies is translational research. So we created the Therapy Expert Board (TEB) – a group of experts that 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 and a lot of partners were coming to us for advice on how to design clinical trials and outcome measures. So we created a 3rd board, the Clinical Expert Board (CEB), where we brought together a set of world-class experts, who are helping us help our partners think about how to design clinical trials.
We have come a long way since the inception of STAR in 2008. Over the last 2 years, the CMTA has financed 40 active projects and spent 3.5 million dollars 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. Success breeds success. Thanks to the support from all our donors, there is huge momentum and promise.
CMTA Research Update by Disease.
Over the past 7-8 years, we’ve done animal studies, performed HTS, got hits and worked with a company called Genzyme. Today, we’ve narrowed it down to 2 families of compounds which are being fine-tuned in the lab. Genzyme uses a traditional, small molecule pharmaceutical approach. The entire biotech industry is based on an approach where you create biological living proteins and go directly after your target.
In parallel, another company came to us with a very different approach using RNA interference. RNA interference uses little pieces of DNA to get into your nerves and affect the way the cells creates the protein which overexpresses PMP22. We’ve seen promising results in rat testing. This technology is currently used in 2 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: In CMT, there is a problem with small pieces of DNA, so you can send the right DNA via a virus into the nerves, replacing the wrong DNA. 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
Every person with CMT has a big role to play. There are currently 20 Center of Excellence in the US and abroad. You can help by joining our patient registry. Clinicians need as much data on as many patients as possible to help drug companies conduct successful trials. We are also developing “outcome measures” to be able to see the effect of a drug as soon as possible so that we are able to 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 https://www.rarediseasesnetwork.org/cms/inc/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!