Divisional Chief of Medicine at the Vanderbilt University Medical Center, David A. Edwards, MD, PhD, talks about repurposing existing drugs to treat new and hard-to-treat diseases.
Interview conducted by Ivanhoe Broadcast News in 2023.
Each year, the NIH sponsors different off labeled tests. Can you go into detail about that?
Edwards: There are many medications that have already been developed and people are using for other indications or other diagnoses. They could be helpful in other diseases as well. Rather than going through the 10 to 12 year pipeline of developing new drugs, what are the drugs that are out there that could be used for other diseases? It’s much faster in one to two years to have these medications be used for other diseases. The NIH sponsors this, we call them reformulation trials.
How do you know which of the drugs will work on which condition? It is trial and error, is it luck? Do you have any idea of what’s going to happen?
Edwards: At Vanderbilt, we have a database, about over 100,000 patients with their genome, all the data from their DNA in an anonymous database, meaning we don’t know who the patients are, but we know what their diseases were. We can link the changes in their DNA to the type of diseases that they have. When you cluster the changes in their DNA to the different diseases that they have, we can see that some patients with certain diseases have certain DNA. Those DNA, they code for certain things like proteins. We scan the DNA, and we look for what medications are acting on those specific proteins that might help the person with those diseases. Once we know what medications might act on that person’s disease, then we design a trial with that new medication and see if it helps for that disease.
How do certain injections affect some patients physically as opposed to others?
Edwards: There are many ways to treat pain and one is through injections. Wherever there’s a nerve in the body, anatomically, if it’s accessible to an injection, through a needle with some sedation and some numbing medication, we can guide that needle down to where that nerve is and just numb the nerve up. If numbing the nerve up relieves the pain for that region of the body, then we know that that’s a potential target to treat the pain. When it comes to making pain relief last longer, just a local Lidocaine will only last four hours. But what if we add another medication to it and suddenly the pain relief is 12 hours, two weeks, six months? That’s what we’re looking for when we’re looking for medications that we add to injections. Sometimes the injection alone can relieve pain just by washing out the inflammation from the area, patients can get sustained relief.
Do they usually end up doing a lot better?
Edwards: That’s the part of the trial. When you do a research trial, you don’t know exactly who is going to benefit and who is not. You may be testing the medication itself or the injection itself, but every patient is different. Every person is different. How they respond to pain, how they feel pain, that’s all different. That’s part why we do blind research trials. Some patients may get two days, some patients may not benefit at all. We need to do the studies to discover that.
On the topic of blind studies, are the results typically what you expect, or are they typically not? Or is it somewhere in between?
Edwards: We make a hypothesis. Scientific studies start with your hypothesis. You try to prove it wrong. In the case of the study that we’re doing now, we would hypothesize that a patient after an injection with Lidocaine would only get maybe two to three hours of pain relief unless we add the drug. Then we hypothesize that the pain relief may be longer, even up to a day or longer than that. Then we do the study. It’s blinded, we don’t know the outcome at the end of the study, and we see if our hypothesis was correct. Did the patients who had the medication have pain relief that lasted longer or was it false? If it’s false, then we must start over and look for something else.
In San Antonio, these migraine meds on breast cancer and it shrunk the tumor. Where do you see this type of treatment heading?
Edwards: In that study, they most likely had a hypothesis that a certain kind of migraine medication would impact cancer. It sounds like they discovered that it did, and so the next steps would be follow up studies specifically targeting maybe different kinds of cancers or to see if that effect is durable and can be used as a cancer medication. The next step is for the FDA is to put that on label as a treatment for cancer.
When you get “aha” experiences as a doctor when a treatment works or a medication works or something works, how exciting is that for you?
Edwards: It’s very exciting when maybe you hypothesized that you would have a beneficial outcome from your study, and it is beneficial. It’s really rewarding to bring that something new to patients who have suffered so long, especially in the field of pain.
Is there anything else you wanted to add about your study?
Edwards: In this study, it is a blinded study and it’s a crossover trial. What that means is, every patient who goes through this study gets a procedure or a block without the study medication and another one later on with the study medication I as the study lead don’t know which- which medication they got in which block. At the end of the study, I will discover which treatment had the medication and we will decide, or we will analyze the data and then we’ll know if the medication had a benefit. Some patients are getting benefit from the block, we normally do these blocks during medical care. Some patients are getting weeks of benefit. Some patients are getting months of benefit. We just don’t know if it’s due to the block or to the study medication. We’ll find out at the end of the trial. The trial ends at the end of this year and we’ll know that the data results in about six months after that.
Is there anything else that you wanted to add?
Edwards: Yes. People are going to be like, what is this study and what is this drug. At Vanderbilt, I’m a pain physician and so I do a lot of procedures that treat different kinds of pain. We’re doing a study on a medication that we hypothesize will be beneficial for the treatment of nerve pain. Trigeminal Neuralgia is a painful syndrome that patients have. It’s often called the suicide disease because it’s so painful. Patients can’t imagine going on with their life having this pain. We try to bring everything we can. There are no on label treatments for this kind of pain. We currently in the medical field use nerve pain medications to treat it. We do injections to treat it and that’s beneficial and effective for about 50 percent of patients. The concern is the other 50 percent. We’re trying to bring a new medication, put it on label in a fast time by reformulating a medication that’s used to treat ADHD. This ADHD medication, it’s called Guanfacine. It in our hypothesis will be effective for the treatment of nerve pain. What we’re doing is delivering that medication to the nerve, the trigeminal nerve under sedated guided and fluoroscopic guided block to see if it will treat that and relieve that pain. The second thing we want to find out is how long will it work. If it works, our next step is to figure out ways that we can deliver it. Maybe not just by injection, maybe there’s a nasal spray or an oral pill form that we can also use.
This patient that was so well, you don’t know if she got the nerve?
Edwards: Every patient that goes through the trial, one of the injections, they will just have Lidocaine. The other injection they will have Lidocaine plus guanfacine, the study medication. Every patient will get the treatment, we just don’t know which order. Some patients are coming for their first treatment and they’re get four hours of benefit. I don’t know if that’s just the Lidocaine or if they had the study medication. Some patients are coming and they’re getting three months of benefit. I hope that’s the study medication, but I have no way of knowing. I hope that that’s the study medication, but I don’t know until the trial has ended and I can look at the data. The database that we have at Vanderbilt, which is the database of everyone’s genes, this anonymous database that we can look and match drugs to potential treatments. This is called Phenome Wide Association Studies, we call that PheWAS. Here, through complex analysis and mathematical analysis, we can cluster different diseases and then match potential treatments to those diseases. At Vanderbilt, I’m aware of several studies going on where new medications are being brought for diseases that don’t necessarily have treatments just by looking at what we’ve already done in the medical field, what medications are out there and taking these medications, reformulating them and targeting different disease states.
Is there anything else regarding the study?
Edwards: We’ll talk a little bit more. The study is powered to be significant, meaning we have to have enough patients so that we know if the results are valid. It is 30 patients, and each patient gets two blocks. At the end of the study, which we’ll complete at the end of this year, we’ll have enough power to know whether the medication was effective or not. Then the next step is to design another larger trial if it’s effective to use the medication in different forms to treat different patients. We’re really excited about the results so far. Patients are tolerating the procedures very well. A lot of these patients who are coming to our trial haven’t had benefit from any of the things that we have to offer in medicine so far. They’re excited to be part of the trial and we’re excited to offer this to them.
I’m sure their lives as far as activities and moods are probably changing drastically from the medications.
Edwards: Sometimes just the treatment alone, just the injection is enough to at least provide someone with some pain relief in the short term. That’s beneficial for a lot of these patients who haven’t had relief for a long time. Like I said, some of them you would anticipate would be really depressed. If they are getting longer term relief than Lidocaine alone, then they’re excited to be part of this trial and to find out the results for themselves.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
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