Professor David Putrino is a physiotherapist with a PhD in Neuroscience. He is currently the Director of Rehabilitation Innovation for the Mount Sinai Health System, and a Professor in the Department of Rehabilitation and Human Performance at the Icahn School of Medicine at Mount Sinai.  Professor Putrino recently opened the Mount Sinai Cohen Center for Recovery from Complex Chronic Illness in New York also known as (CoRE) and serves as CoRE’s Family Director and is also a member of PolyBio’s Long COVID Research Consortium.

Today's episode is the second in a two part series looking at research into potential treatments for Long COVID.

REFERENCES

1 Polybio Article - A clinical trial of repurposed HIV antivirals in Long COVID

2 Patterson BK, Yogendra R, Guevara-Coto J, Mora-Rodriguez RA, Osgood E, Bream J, Parikh P, Kreimer M, Jeffers D, Rutland C, Kaplan G. Case series: maraviroc and pravastatin as a therapeutic option to treat long COVID/Post-acute sequelae of COVID (PASC). Frontiers in Medicine. 2023 Feb 8;10:1122529.

3 Polybio Article - Long COVID low-dose rapamycin clinical trial

4 Polybio Article - Lumbrokinase Long COVID & ME/CFS clinical trial

Funmi Okunola: [00:00:00] Welcome to Long COVID - The Answers. Today's Episode is the second part of a two-part series entitled “Long COVID Research and Potential Treatments”. In this Episode we'll take a closer look at the clinical trials Professor David Putrino is conducting, focusing on some of the potential treatments for Long COVID.

I'd like to introduce Professor David Putrino. David is a physiotherapist with a PhD in neuroscience. He worked as a clinician in Australia before moving to the United States to study computational neuroscience at Harvard Medical School, the Massachusetts Institute of Technology, and New York University.

He has served as a faculty member at Weill Cornell Medicine and Burke Medical Research Institute. He is currently the Director of Rehabilitation Innovation for the Mount Sinai Health System, and a professor in the Department of Rehabilitation and Human Performance at the Icahn School of Medicine at Mount Sinai.

Welcome, David.

David Putrino: Thank you for having me. It's great to be here.

Funmi Okunola: David, do you have any conflicts of interest to declare?

David Putrino: I have no conflicts of interest to declare.

Funmi Okunola: Great. We're going to do a deep dive into the trials that Professor David Putrino is actually doing and why. Two of the drugs that you are clinically trialing as potential therapeutics for Long COVID are repurposed HIV antivirals. What caused you to look in this direction for treatments for Long COVID?

As we were thinking about repurposing HIV drugs, some of the drugs that really caught our eye were Truvada and Maraviroc. Truvada, in early clinical trials showed some efficacy against SARS-CoV-2. Truvada is also a really powerful anti-EBV drug. It has the ability to attack EBV quite effectively and given the work that we did with Akiko Iwasaki's group at Yale showing that EBV reactivation was one of the most prominent distinguishing features of Long COVID when we were [00:03:00] doing deep immune profiling on these patients, it seemed like a good idea to us to see if anyone was responding to Truvada.

Similarly, with Maraviroc, there has been some early evidence to suggest that Maraviroc might be effective in blocking the ability of the SARS-CoV-2 virus to enter cells. So, our theory there was even if we can't eradicate SARS-CoV-2 maybe we can stop it from infecting cells in such a way that it's maybe less able to replicate.

It's less able to circulate in cells and cause all sorts of damage, and so was another drug that we wanted to trial. Again, due to the work that's been done in the field of HIV it was certainly something that had a good safety record, and we felt confident that we could try it quite easily.

David Putrino: No worries.

Funmi Okunola: A lot of the positive outcomes from this trial - alleviation of neurological, cardiovascular and respiratory symptoms, were achieved by using these drugs together. Why aren’t you using the combination of Maraviroc and Pravastatin?

We're really interested in this sort of experimental medicine approach of applying single molecules to patient populations, understanding what constitutes a responder and a non-responder, and then using that understanding to run larger clinical trials on single drugs where we have a much more strict and stringent inclusion criterion, and then moving into multi-drug trials where we can test multiple drugs at a time using more sophisticated clinical trial methodologies such as adaptive platform trials.

In part one of this episode, we were talking a little bit about endothelial damage and inflammation and so on and so forth, and how endotheliosis may play into the overall pathology of Long COVID. Well, one of the most effective ways to address endotheliosis is of course the use of statins.

From just a general treatment approach it really does make sense to do something like that. However, right now we're trying to understand the mechanisms of single drugs - what they're doing to people. We want to understand if someone responds really, really well to a single drug, why is that? What really was driving that improvement that we saw. That's why we chose to do a single drug as opposed to a combination drug approach.

Individuals with Long COVID experience more than 200 symptoms, and the different phenotypes or classification of Long Haulers are not well defined. How are you identifying the most suitable group of patients who are likely to benefit from the use of each of these drugs in your clinical trials?

David Putrino: It's a great question, and it's a challenging question. I'll preface by saying all opinions are valid here. I'll tell you what our approach is, and I'm not sure that it's the right one, but it's the one that we've selected, and I think the key phrase here is ‘experimental medicine’.

We do a full immune panel including immune testing that can't be purchased or done using traditional blood. We're working with partners like Akiko Iwasaki. We're doing very detailed neurological assessments, and we’re doing very detailed endothelial assessments and what have you so that when we do see responders, we can understand who responds.

I think possibly one of the most relevant examples of that would be low-dose naltrexone. You will hear a large swath of people saying, “I tried low dose naltrexone, and it did absolutely nothing for me,” and you'll hear other people say, “It has turned my life around.”

Funmi Okunola: So, from what you've just stated, am I understanding that you're quite broad. You take people into the studies - at present you’ve got a positive test for SARS-CoV-2, but then as you progress through the study and see who responds and who doesn't, you do all of these very detailed tests of their immune system and their endothelial system to parse out phenotypes in that way [00:11:00] rather than saying, “Oh, it looks like you might have MCAS and “it looks like you might have a clot” pre-study, and then separating them off beforehand. Am I correct in my understanding there?

David Putrino: That's correct. The only thing I'll say is slightly different is if we are testing a drug that, for instance, were we to test the monoclonal in a clinical trial we might slightly alter that approach.

Now we would still at that point cast a wide net. We wouldn't say, “Hey, we're only going to recruit [00:12:00] people who have spike protein circulating around in their plasma.” Because still again I would really like to know if we see no evidence of viral persistence, do you not respond to the monoclonal?

Funmi Okunola: Oh, it's just fabulous. I'm listening to you. I'm really hopeful there's not just going to be treatments but even a possible cure with your whole approach. It's just so exciting and it just gives real, real hope. So lastly, can you talk about the new Cohen Center for Recovery from Complex Chronic Illness or CoRE at Mount Sinai and what you hope to achieve there?

But the reason that we set up Centers that are Hybrid Clinical and Research is so that the researchers are always talking to the clinicians, who are always talking to the patients, who are also always talking to the researchers, and we have this cross pollination and community co-design environment where if we see something is working, we can quickly scale it into clinical operations. The center is designed to take up insurance in the U.S. because we feel that there are too many cash only clinics that are popping up all over the place, and that's just not sustainable for people with Long COVID who are very, very sick.

Our mission is to be a Center that launches a thousand Centers - to be the Center that shows thousands of other groups who want to build their own Center how to do it, and how to do it in a way that is cost effective and accessible to the patient population that needs it so much.

So that's a little sort of an insight into what we're building, and it's a learning process. We've made a lot of mistakes along the way. We've learned from them. We take feedback, and we try and just continually upgrade our Center to keep making it better and better for the patients.

David Putrino: That would be really helpful for us as well.

Funmi Okunola: Thank you, David for taking the time to enlighten us today and to give all of us hope. Thanks to you, your team at Mount Sinai and all the scientists at PolyBio for providing hope and help to individuals around the world suffering with Complex Chronic Disease.

David Putrino: Thank you so much for having me helping to get the word out. We really appreciate the programming that you run, and it's definitely helping spread education to a lot of people. Thank you.

Funmi Okunola:

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