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"The Brain Captivated Me" - Ataxia Researcher Dr. Pravin Khemani

Dr. Pravin Khemani has been fascinated by human physiology and medicine since he was a young child, and after satisfying another strong interest by getting an engineering degree, finally found his home in neurology, specifically dealing with neurodegenerative diseases.

He's now a neurologist at Swedish Health Services in Seattle and a Principal Investigator in a clinical study evaluating the effectiveness of a drug called troriluzole, developed by Biohaven Pharmaceuticals, in slowing the progression of spinocerebellar ataxia (SCA). Learn about the disease, the trial and what drives his passion for patient care and research in this engaging interview.


Read the transcript:

Dr. Khemani: If you are somewhat restless of nature and want to think and think about how to solve a problem, then the neurosciences and the neurological sciences is a fantastic field,

Michael Carrese (host): That curiosity is part of what motivates Dr. Pravin Khemani to work with patients with movement disorders, including those with spinocerebellar ataxia or SCA. In fact, he's one of several doctors around the country leading a trial to determine if an investigational medication called troriluzole can slow down and improve SCA symptoms.

This is Behind the Research with Biohaven. I'm Michael Carrese, and we're going to spend most of our time together today learning about how this study works, what it's hoping to accomplish and how to get involved. But first, I wanted to know more about Dr. Khemani and what led him to his current position as a neurologist at Swedish Health Services in Seattle and his role as one of the principal investigators for the SCA study.

In a recent interview. I began by asking him about what sparked his interest in medicine.

Dr. Khemani: I'd always been interested in medicine and by the human anatomy, human physiology and truly by the mysteries of medicine.

I think very early on in my childhood, I wanted to be a physician. But then as I was growing up, perhaps a little bit of peer pressure from friends who were going into the engineering field and certainly from family, I just decided to go down the beaten path, so to speak.

After I finished my engineering, you know, I became restless again. And this little voice in my head said, 'well, if you really want to do medicine, you should explore it.' And before knowing it, I was in medical school. And in medicine, I was more interested in the neurosciences than other fields. The brain sort of really captivated me. I volunteered in the neurotrauma unit at Detroit Receiving Hospital for about six weeks or so, and I was absolutely awestruck by the ability of the brain to recover, even after serious head trauma for people to come back to consciousness. And I don't know if you remember, but 1990s was the decade of the brain. I think we were just beginning to unravel the mysteries of the mind and consciousness. And I said, well, what better field to go into than the brain and neurology and neurosciences. And that's how I ended up in the neurosciences.

Host: I've heard other neurologists talk about neuroplasticity as being the thing that absolutely fascinates them. Is that partly what you're referring to?

Dr. Khemani: Yes, to some extent, neuroplasticity - the ability of the brain to be able to recover function after trauma-the ability of the brain to sprout new connections. The mysteries and the unknown sort of unexplored frontiers of the human brain are one of the things that fascinate most of us who go into neurology.

But then the other is the ability to extrapolate the function of the brain through a physical examination. and particularly in my field of neurodegenerative diseases - Parkinson's disease, the cerebellar ataxias, progressive supranuclear palsy - a lot of these neurodegenerative diseases, we still don't have specific blood tests. So, we have our physical exam, our analytical skills, good intuition that helps us come close to the truth. All of that was probably, you know, an influence in me selecting that field. It was a combination of many factors.

Host: So what you're talking about is all of the things that you ask your patients to do - the walking and moving of limbs and so forth during an exam - that you are looking for very subtle indications and trying to read with some precision from those gross motor movements what's happening in the brain?

Dr. Khemani: Exactly right. The art of the neurological examination, the science of the neurological examination is absolutely essential to master in order to come close to the truth. And truly, these are the techniques that are also outcome measures in clinical trials. You know, we have to perform a very good, accurate exam in order to keep track of whether a particular intervention is working or not.

Host: So let's talk about the Biohaven SCA trial. Why don't you tell us about who's involved, what's involved and what drug you're investigating?

Dr. Khemani: We are doing this trial in several centers across the country. When I was at University of Texas Southwestern, I did this trial there and the results of the trial showed that this particular drug that we are studying called troriluzole may be particularly effective in certain subgroups of the ataxias. So, in this next phase of the trial, we are trying to recruit people who we thought could have benefited from this drug.

Spinocerebellar ataxia is one, two, three, six, seven and a few others that we think may benefit from this particular drug. it's a more focused trial and it's underway even in times of COVID 19. We are able to do a teleresearch in which we can talk to people, do a lot of the intake online through platforms such as what we are using today, Zoom, etc. And now that our clinics are open, by the way, we are actually having people come in for their face to face evaluation. There was a hiatus over the past couple months, as you know, as we were practicing physical distancing.

But now, with masks and taking appropriate precautions, we have restarted the process of recruitment, screening and continuing to test the subjects in a longitudinal fashion like the trial demands over 48 eight weeks from the time they are screened and enrolled. So, this particular drug is being studied now. It's a placebo-controlled trial. So not everybody gets the active intervention, which is troriluzole. And what we are studying is the outcome, if you will --- is their walking, improving? Is their coordination, improving? And how do you determine that? Through that physical exam that I mentioned earlier. There is a scale that we perform and we score that at regular intervals to document change.

Host: So let's talk about trials generally. People obviously may approach a trial with some concern about, let's say, the safety of the medication that's being studied, about cost, about other sorts of unknowns. But there are also often misunderstandings, I think, about how a trial is run and who plays what role, what role did the drug companies play versus clinicians. And also what is guiding all the decision making and how a trial is put together and executed. So, can you fill us in about that?

Dr. Khemani: The role of the drug companies is to devise a protocol based on really valid scientific principles and using scientific methodology and float that protocol to the various centers. And we read that protocol and determine if there is merit in doing the trial with the particular drug company. We look at the compound, look at the biochemistry, read preclinical, maybe even animal data and determine "oh, this looks like a compound that shows a lot of promise. And we would like to be involved in this particular trial." That's where it starts.

Then there is a whole review process. there is an independent review board that looks at the protocol, which has no conflict of interest because that independent review board is not part of the drug company or the principal investigator. They're very independent. And it is their job to use the ethical principles of clinical scientific research the ones that are outlined in the the Belmont report, in the common rule, in the Nuremberg Code, they're all of these fundamental ethical principles that guide clinical research. So, both the Principal Investigator and the Independent Review Board are bound by those principles that guide not only clinical research, but medical care to ensure that this trial provides social has social value, that it's not just being done for the sake of being done, number one. Number two, that people will be able to understand the protocol and provide informed consent. Number three, there is volunteerism ...within the informed consent, which outlines all the risks and the benefits and the pros and cons of the clinical trial, there is a very important proviso that participation in clinical trials is purely voluntary.

I really do believe it's the highest spirit of volunteerism because you are entrusting your brain, your body to a principal investigator and that requires a very high level of trust. And it is very important that we don't violate that trust. There needs to be scientific validity when we look at the methodology in the trial. We have to be convinced that this is valid. This is proven methodology. We are building on fundamental scientific principles. That is really important. And the respect for all participants at every point of the trial is very important. So that's probably a long-winded answer to the question or the concern that trials are maybe biased towards a certain outcome. It's also important for the subjects to understand that the drugs that we study are not an automatic panacea. We don't know if they're going to work. We do know it has potential. That's really important.

Host: Absolutely. And you have heard other principal investigators say that even if a trial is not, successful -- in other words, the drug that was being investigated didn't turn out to have the effect that everybody was hoping for -- there is still tremendous value in that because you now know a lot more than you did before.

Dr. Khemani: Absolutely. We know that that particular drug or its class is likely not useful. But the other most important thing is, is to do, if you will, a dissection of the trial and determine why was the drug not successful? Was it because the correct outcome was not measured, which is very important. if the outcome measure is not accurate, you will not see a signal. For instance, the exam we are doing for the Biohaven trial, SARA, it is a gold standard outcome for ataxias. And so that is an accepted outcome and that's what we are using to document change over time. But there are several other trials in which the outcome measure may not be appropriate and the intervention actually is potentially useful. And if only a different or better or more appropriate outcome were used, you would have actually seen a positive signal. So there are many things in a trial that inform its success or failure.

Host: Clearly. And a lot of safeguards and scrutiny and accountability and all the things that should be there when you're doing people's health care.

Dr. Khemani: That's right.

Host: So talk about the SCA community a little bit. My understanding is that they're pretty tight knit group. And I wonder if you could just talk a little bit about some of the interactions you've had with those folks and what you like about working with them.

Dr. Khemani: Yeah, community is a great word. The largest community that I know that probably brings people together is the Nationally Ataxia Foundation. And then there are regional and local chapters. And we have one of those in the Pacific Northwest, the Western Washington Ataxia Chapter. It's a very large chapter run by Sherry McLaughlin and a large, wonderful group of people, which you would call community. And I've had the good fortune to to go up there and talk to them and interact with them and present to them. And it's a wonderful, wonderful group of people who interact with each other and help each other out, inform each other. the ataxia community is extremely knowledgeable. I learn a lot from people with the ataxias in terms of their resourcefulness. The physician and the caregiver just has to have an open mind to say, well, I'm here to learn from you guys. So what's new? What do you what have you guys been up to? Teach me so I can so I can teach the rest of my patients. So therein lies the the benefit of having people with the SCAs come together.

Host: Yeah. Clearly tremendous value in all of that. So the other thing I want to try to get at is how do you describe what gets you out of bed in the morning, so to speak, and eager to see your patients and to be as busy as you are with the research and everything else that you're doing? What's driving you?

Dr. Khemani: Well, the alarm helps. (laughs)

Host: I guess I set myself up for that. (laughs)

Dr. Khemani: Other than that, I suppose what got me into into medicine in the first place and what's been getting me out of bed all of these years is the same thing: is interacting with patients, interacting with patients and caregivers. I think that is one of the joys of medicine. And then the ability to learn something new and different. In order for me to educate patients first, I have to learn from them. I have to hear what they're saying. So that's a process of education as well. every interaction is unique. There is a sort of air of mystery which keeps me intellectually stimulated. It makes me think on my feet. I don't think I need to do Sudoku. And that's because I probably am terrible at it. (laughs)

Host: You have enough brain stimulation without it, though, right?

Dr. Khemani: Yeah, exactly. So, this is my New York Times crossword puzzle and my Sudoku. If you are somewhat restless of nature and want to think, and think about how to solve a problem, then the neurosciences and the neurological sciences is a fantastic field.

Host: So just wrapping up, what's your message to people who are listening to this and might be thinking about participating in this trial? What do you want them to understand about the process or about the contribution they potentially can make?

Dr. Khemani: I think being informed is the first and fundamental thing. If you know your mutation, I think it's great to be part of a clinical trial that has potential to treat what we think is wrong or the problems that are caused by that mutation so the treatment is really customized to that particular subtype or type of ataxia. We really don't have a lot of those, but I think there is a lot of promise.

And by doing these trials, positive or negative, we will get closer and closer to the truth to say, "okay, you know, these two drugs or three drugs work for SCA one, two and three really well. And that's not possible to do in a lot of other diseases. So that's why it's important to take part in clinical trials to help the scientific community understand which drugs are working for which particular disease. And ultimately, I do believe it comes back full circle because you've participated in a trial, you have contributed to science, and we have found out that this drug is not working, but this is now working. You know, you can benefit from your own participation. But again, I think spirit of volunteerism is what drives people to take part in clinical trials. And I think there's a lot of hope and optimism for treatment of these ataxias. I think those, to me, are good reasons to take part in clinical trials and also to know that there are some fundamental principles of clinical research and ethical principles that guide clinical research that we abide by. And so I hope that helps a little bit, helps the community understand a little bit about what drives us to do research and perhaps what should interest them in being part of a research trial.

Host: Well, thank you very much, Dr. Khemani for being with us today and best of luck with the study.

Dr. Khemani: Thank you, Michael. I really appreciate the opportunity to talk to you and to spread the message about clinical trials and ataxia. Take care of each other, folks. Thank you.

Host: And if you want more information on the study we've been discussing, visit This is Behind the Research with Biohaven, I'm Michael Carrese. Thanks for listening.

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