Episode 3: Opeyemi Olabisi

Laurel Damashek: [00:00:00] Welcome to GN in Ten, a bite sized podcast brought to you by the International Society of Glomerular Disease. Our hosts are nephrologists and glomerular disease experts Dr. Kenar Jhaveri of Northwell Health and Hofstra University on Long Island, New York, and Dr. Koyal Jain from the University of North Carolina Chapel Hill.

Kenar Jhaveri: Welcome everybody to GN in Ten. Today we have a special guest who is actually from Koyal's rival institution, Duke. Opeyemi Olabisi, welcome.

Opeyemi Olabisi: Thank you for having me.

Kenar Jhaveri: Welcome to GN in Ten, and we would like you to just tell us a little bit about yourself first and how you got interested in the field of glomerular diseases.

Opeyemi Olabisi: Yes, thank you Dr. Jhaveri and Dr. Jain. Thanks for having me. As you mentioned, I'm an associate professor of medicine at Duke, and I always say that I'm a nephrologist by day and a kidney researcher by [00:01:00] night, and I do spend a lot of time at night. So by way of background training I did all my MD PhD training at Albert Einstein College of Medicine, not too far from you, Dr. Jhaveri, in New York. Went to Boston where I did my residency fellowship in nephrology at MGH and Brigham. At the time I was finishing my residency, that's when Martin Pollak published the Science paper on APOL1.

That's how I became interested in APOL1. So I went to Martin's lab to do a research postdoctoral work. And that's how it started for me, over 10 years ago. So I haven't looked back since.

Koyal Jain: I really admire you for your work that you've done with the underrepresented community. I have a question there. So Black patients are often underrepresented in clinical trials despite a high burden of kidney disease, and I know that's your focus, but why is that in your opinion and what can we do as a community to change it?

Opeyemi Olabisi: That's a great [00:02:00] question Dr. Jain, and you are right. If you look at the burden of disease, African Americans represent about 13 percent of U. S. population. Patients on dialysis, national average is around 30, 31%. If you look in our area here, North Carolina and down south, that number is as high as 35 percent in some places, 40 percent. Now, if you look at therapeutic clinical trials, and I'm not talking about trial on dialysis, for people who have already developed end stage kidney disease. But for therapeutic trials slowing the progression, African Americans are significantly underrepresented.

In some studies, less than 5%. So about 35 percent on dialysis, less than 5 percent in therapeutic trial. And that has multiple factors to it. In fact, I started off not doing this type of work originally, but recognizing that even all the basic science work I was doing at the bench will really amount to nothing if we can't really engage the [00:03:00] community.

That's my path to it. By training, I'm a basic molecular biologist. But now I actually spend more time, because I feel so strongly about this, that we have to engage the community. There are certain impediments that have been in the way for this.

One is that generally people always say maybe African Americans are not interested in research. They are, in my experience, if you ask and you approach the right way. There's a significant trust deficit between the African American community and the biomedical research entity, and that lack of trust is well earned.

It's not just the Tuskegee, it's not just Henrietta Lacks, it's just the way the research enterprise is set up. People are very busy. Most of our research are set up in the academic institute. We ask people to come in. When you have somebody that's doing two or three jobs, they don't have time for a study visit, schlepping over to UNC or Duke.

Now, so the nature of research is not conducive for many patients to participate. And [00:04:00] also sometimes the way we structure our research, we don't actually explain why. I think that's a major gap. If you say, okay, participate in this study, people are thinking, how will this benefit me or my community?

So addressing those issues in my mind are things that really moved me to spend my time, to divvy up my time between the bench and the community. I spend as much time in Black churches as I do spend in the cell culture hood because of that realization.

Koyal Jain: The trust piece is so important and I feel like that's something that affects the Black community and also the other URM.

Patients coming in saying, why should I trust you, right?

You're a new physician that I haven't met before. I've had so much history with the medical system. Why should I come and trust you and get involved in a clinical trial when there's a history of research that's against me technically. And so creating that relationship, hearing people is so important. Listening to them, collaborating, giving them a voice and you do that beautifully.[00:05:00]

Opeyemi Olabisi: Thank you. That's so important. People always want to know why. Why is this research important?

So I think the onus is on us to actually start with why. Now, the community knows that the burden of disease is high, but here we are articulating the why to the community.

Kenar Jhaveri: One of the questions that comes up then is: do you think, not just to African Americans, but women, other minorities, the fact that we don't have trialists of color or women, it probably makes a big impact. If I went to a South Asian patient, as opposed to a white man going to a South Asian patient, it might make a difference in some of the recruiting that I speak the same language the same culture, and the patient might trust me better in terms of recruitment.

Opeyemi Olabisi: I 100 percent agree with you, Dr. Jhaveri. What is trust? Trust is the, in my view, is the integration of past experiences. And as human beings, part of what we use for that [00:06:00] heuristics, for that shortcut is, does this person have some link with me?

Do we share, have something in common? And common identity helps a lot. I will tell you, my team is majority African Americans by design, because as we go to black churches, there are many barriers that we have to overcome. We want to overcome that very quickly.

So when we go to the churches and they see the researcher looks more like them, it also lowers that barrier a little. Now, it's not automatic. I will tell you this. Coming from many of these institutions some of us work in, those institutions also have history

of not welcoming some of this underrepresented group. We have to overcome that as well. But as we overcome those barrier, the barrier of race, barrier of gender ,barrier of background, increase in representation among the researchers themselves. I feel strongly that it helps to lower the barrier of trust, and to your point, it increases [00:07:00] participation.

Koyal Jain: This is something that's also true for nephrology or medical education and students who come into medicine and then they see people who look like them . And I've had people come up to me and say, we never even thought that we would have an Asian woman who is leading this course for us, and thank you for doing what you're doing. So I think representation actually does matter, and not just in trials, but also research, education, and clinically in so many different fields.

Opeyemi Olabisi: Absolutely. Thank you.

Kenar Jhaveri: APOL1 discovery has been one of the best discoveries in nephrology, in my opinion and targeting that is just phenomenal. I think it's going to change the landscape of kidney disease.

What do you think, and when do you think this is going to be commercially available for our patients?

Opeyemi Olabisi: I think the story is quite amazing. For decades in the U. S. we've known that African Americans have high burden of kidney disease. A lot of people in the United States funded by NIH were starting to say, okay, [00:08:00] when you see a black person on dialysis, he or she tends to have somebody else on dialysis. So pointing to genetic factor.

The culmination of that work when Jeffrey Kopp and others identified chromosome 22, Martin Pollak took that further and identified APOL1.

Now that was 2010. We now have two clinical trials. There are multiple coming.

Of course, I'm biased because I'm an optimist, but if you look at the trajectory of the discovery to the identification of potential therapeutic compound to where we are now doing a phase 2, phase 3 trial, it's been pretty breathtaking. If that path continues, I would expect that in the next three years or so, we should have something in clinic.

Koyal Jain: This is phenomenal amount of research and work that has happened within 13 years. Do you think we'll eventually get to a point where we can prevent APOL1 associated diseases, right? Now we're having to treat them, how can we get there that we don't have them?

Opeyemi Olabisi: You are right on the money. For example, in the US, we know [00:09:00] that about 13 to 15 percent of African Americans have the high risk APOL1 genotype.

That is more than six million people in the U. S. And that's a small population compared to people in Sub-Saharan West Africa, where I come from, compared to people in the Caribbean, compared to people in South America.

So the population in the world of people that actually are potentially going to benefit from not just the therapy, but also the prevention is huge.

It's the APOL1 protein that causes injury to the kidney. My group is leading a study that blocks APOL1 production repurposing an existing drug, baricitinib.

If that study works, the next place we are looking is to identify people who have not yet developed kidney disease to say, can we apply the same intervention to actually preventing this disease from starting altogether?

Kenar Jhaveri: That was interesting. What is the mechanism of that drug you just mentioned?

Opeyemi Olabisi: Baricitinib is a JAK1/JAK2 specific inhibitor. Rheumatologists have been [00:10:00] using baricitinib for the last eight years to treat rheumatoid arthritis. It turns out that the production of APOL1 is regulated by multiple cytokines, not just interferon.

And what our study found is that most of those upstream cytokines work through the same pathway: the JAK-STAT pathway. When we block that pathway, we block APOL1 production altogether and APOL1 induced injury in the cell in the preclinical model.

We are predicting that will most likely do the same in patients. So we'll hopefully we'll find that out.

Koyal Jain: So with that, Dr. Olabisi, do you mind telling our listeners a little bit about the CARE and JUSTICE program?

Opeyemi Olabisi: So CARE stands for Community APOL1 Research Engagement, and JUSTICE basically is an acronym that comes from JAK-STAT inhibition to reduce APOL1 mediated kidney disease. So we are doing care in order to do justice.

We're aiming to address four problems. One is the high burden [00:11:00] of kidney disease in the African American community, and APOL1 contributes significantly to that.

Two, lack of disease awareness specifically, lack of awareness of APOL1 mediated kidney disease. Most African Americans that have APOL1 mediated kidney disease don't know they have it. And thirdly, lack of specific treatment. Fourthly, under representation of African Americans in clinical trials.

With CARE, we go to the community and provide information in a way that people can understand it. So we go to churches, we go to community centers, we said we go to highway and byway, wherever people are.

We actually provide screening. How do we screen for kidney disease? In this context, we look for albuminuria. How do we screen for APOL1? We take saliva. So if you have high risk APOL1 and you have protein in your urine, we also will collect blood to measure your GFR.

It's both informational and also provides an opportunity for free [00:12:00] genetic screening for APOL1 and also for albuminuria.

And if you want, we also provide genetic counseling.

That is the CARE part of this. Now, people that have clinically significant kidney disease, and we define this as having high risk APOL1 genotype, proteinuria of 300 mg per gram or higher and having either biopsy proven FSGS or clinically diagnosed hypertension attributed FSGS.

If you fall in that category and your kidney disease is not at end stage yet, you have opportunity to participate in a Phase II randomized control trial of baricitinib, where you'll be randomized to receive baricitinib or placebo on top of whatever else you are taking.

The unique attribute of JUSTICE is to address the participation issues. Only the first visit requires you to come to Duke, and we pay for that. The rest of the study, we come to the community, we come to your house, we come to your job, we come to wherever you tell us is [00:13:00] convenient for you.

A lot of our participants do two or three jobs, and they tell us, okay, between four and five, I will be going from one job to the other, that's when you meet me. We are flipping where this study is being done, we are meeting people where they are. I'm really quite excited about this study.

Koyal Jain: That is remarkable,

Kenar Jhaveri: Amazing. This is going to hopefully change the whole landscape of nephrology. Dr. Olabisi, so our last question is we ask all our contestants, I feel like I'm in a game show. It's a contestant.

Koyal Jain: So the listeners, Dr. Jhaveri just called the contestants. He's going to probably, you're going to probably win a prize

Kenar Jhaveri: I know, right? You're going to prize if...

Opeyemi Olabisi: now I'll win prize.

Kenar Jhaveri: ...you name your favorite GN. What's your favorite glomerular disease?

Opeyemi Olabisi: Wow. That's, I would say that's an easy and a tough one.

Kenar Jhaveri: Don't say FSGS.

Opeyemi Olabisi: I was gonna, in fact, I was gonna,

Koyal Jain: Apart from FSGS.

Opeyemi Olabisi: I'll probably pivot, I'll say APOL1-mediated kidney disease. A lot of the kidney disease caused by APOL1 seems to affect the glomerulus in a [00:14:00] specific way, especially the podocyte. We don't understand why the podocyte is so vulnerable to this gene. So APOL1 mediated kidney disease, and this includes FSGS, of course, will be my favorite GN.

Koyal Jain: That was a very smart answer.

Kenar Jhaveri: I guess he wins the prize then, right? The contestant has won.

Koyal Jain: Perfect. Thank you so much, Dr. Olabisi. This has been wonderful. We've loved to get to know you and your projects.

Opeyemi Olabisi: Thank you and I will be remiss if I can't mention that. audience members that are interested in learning more about this can go to www.kidneycareandjustice.com, or they can email us at care.justice@duke. edu. Clinicians, we have a powerful impact on encouraging our patients to participate in trials, and when we know about those trials, we have the ability to encourage.

I'm hoping that we'll hear from many of our audience and people in the [00:15:00] community. Thank you for having me.

Kenar Jhaveri: We're signing off from GN in 10. This is Kenar and Koyal.

Laurel Damashek: This has been GN in 10 from the International Society of Glomerular Disease. You can listen and subscribe wherever podcasts are found and tweet at us at ISGDtweets. Thank you for joining us.

Kenar Jhaveri: That was fun. A lot of fun.

Koyal Jain: I think next time we should just give out Dr. Jhaveri's phone number to everybody and say, Hey, he's going to give you prizes.