Generic Solutions
| November 25, 2020Medical researcher Moshe Rogosnitzky taps existing drugs for new uses
Photos: Elchanan Kotler
How did Moshe Rogosnitzky — a soft-spoken, erstwhile kollel yungerman living in Eretz Yisrael, with not a degree to his name — help determine the course of President Donald Trump’s coronavirus treatment last month?
Among the battery of medicines prescribed for the president by the doctors at the Walter Reed National Military Medical Center was a drug called famotidine — better known as Pepcid, an over-the-counter remedy for excess stomach acid. Given the president’s reputation for being more prone to giving ulcers than getting them, it might have seemed a curious choice. So how did these high-level physicians come to prescribe Pepcid for coronavirus?
Here is where Moshe Rogosnitzky comes in. As it turns out, he headed the groundbreaking research on famotidine that formed the basis of the doctors’ decision.
“We were the first ones in the medical literature to propose it as a possible treatment, following an in-depth literature analysis of potential anti-COVID-19 candidates,” says Rogosnitzky in an interview at Mishpacha. “I don’t think President Trump knows that a high-school dropout in Israel was the one to first propose it... It just shows you that by following a very low-cost, low-tech approach to the problem, rather than utilizing all the supercomputing we have now, and all the research labs, you can sometimes reach the same solutions, or even better ones, much earlier on.”
Moshe Rogosnitzky (pronounced “raw-gauze-NIT-ski”), only in his late forties, has already had an extraordinary career. He is the cofounder and executive director of the MedInsight Research Institute, and describes himself as “a research scientist, innovator, and inventor of major medical breakthroughs.” He consults regularly with top experts in multiple fields of medicine around the world, and his work has saved countless lives.
His main line of work is what he calls “real-world drug repurposing.” This is essentially what was behind President Trump’s treatment with Pepcid, among a cocktail of generic drugs. Reb Moshe describes how research on the drug — which is still ongoing, and is not yet considered conclusive — led doctors to prescribe it for COVID-19.
“Pepcid has a protective effect on the cardiovascular function, which is an issue affecting COVID patients very much,” he says. “And it has very potent antiviral effects. Back when we did our research, we didn’t know that it has a very powerful effect against SARS-CoV-2, which is the virus that causes COVID-19. That came out later, when other researchers began looking at it. We were just looking at it rationally — this drug is over-the-counter, safe, has been around for many, many years, potentially can help people at least with the cardiovascular dysfunction, plus it has antiviral effects. Why shouldn’t we try it?”
As a child growing up in South Africa, Moshe did not have a native interest in the field of medicine, but his own experience as a patient spurred him to learn more about what he would go on to make his life’s calling.
“Just so you understand, I had no interest whatsoever in medicine, and in elementary school, biology was my worst subject,” he recounts with a laugh.
At age 14 he enrolled in yeshivah ketanah and left the world of secular studies behind altogether. But in his late teens, he experienced what he describes as “a personal medical challenge.” The doctors he consulted became embroiled in major disagreements about his case.
“It led me to read up extensively on the medical literature,” he says. All that reading kindled an interest in the world of medicine, which only grew as time went by.
Even after moving to Israel, getting married, and engaging in some business activities alongside his kollel studies, Moshe kept up his voluminous reading of medical studies and books. Word soon got out that this British-born yungerman was astoundingly knowledgeable about medicine, and had a mental library of lesser-known drugs and treatments that may have been non-protocol, but were still unusually effective. Soon patients who’d been categorized as hopeless or terminal began asking him for medical advice. Ultimately, that lead to a career in personalized medicine consultancy, which lasted 18 years.
Moshe didn’t suffice with the literature alone. “Whenever I came upon a finding of interest, I would reach out to the researchers, enter into discussions, often get on a plane to visit them, and that way developed relationships with researchers around the world,” he says. “Innovative researchers tend to be very accommodating and friendly to people who take the time to study their discoveries, and are interested in translating their findings into clinical benefits for patients.”
Since then his career has taken off, driven by his own ravenous curiosity and a proven ability to spot patterns and connections between disparate items that others might have missed. Veteran medical practitioners and researchers who work with him are often stunned when they discover he has no formal medical training. He once published a paper on a remedy for Crohn’s disease and got a call from the lead researcher, Dr. Jill Smith, as it was going to press.
She asked him, “Moshe, the editor of the American Journal of Gastroenterology called me now and says the paper’s missing your title. What are you? Are you an MD, a PhD?”
He said, “We’ve been working together five years, and you’ve never asked this question once.”
Nevertheless, he is quick to wave off any personal acclamations.
“I take no credit for this,” he demurs. “I’m humbled by a role which HaKadosh Baruch Hu has destined me for, and every step of the way I’ve seen tremendous siyata d’Shmaya. And it’s impossible to attribute the way my career has advanced to anything but that.”
The COVID example is illustrative of much of Rogosnitzky’s work: Instead of developing a precise new cure, he aims to match up a preexisting drug’s beneficial effects against the pathophysiologies — the harmful manifestations of a disease.
“What we’re looking at with pathophysiology is, how does the disease express itself in the body?” Rogosnitzky explains. “For example, fever would be a pathophysiology for a particular disease, but it’s also common to many diseases. Hypercoagulation. Lung dysfunction. All these things are pathophysiologies.”
Fighting a disease through targeting its pathophysiologies is, in a sense, an attempt to outflank it rather than attack it head-on, says Rogosnitzky. Instead of looking for the magic bullet that will kill the virus, or the tumor, it’s about making the body an unfriendly place for the disease to be in.
“Rather than look at a disease and say, okay, we’re going to go ahead and kill off this virus — which is going to be very difficult to do, and to prove, and it will take time — let’s instead see how the disease presents in the body, how it expresses itself. And this is really the type of approach that’s followed in intensive care units when a patient shows up.”
The main advantage to this approach is that there already exists a formidable arsenal to assist in this fight: 9,500 drugs approved worldwide.
“We believe that in the bank of drugs we have now, the 9,500 drugs there are in the world, we have the answers for virtually all diseases,” Rogosnitzky says. “Around 500 of them are still patented. So there’s opportunity to work through the other 9,000 off-patent drugs — the generic drugs — and look at the impact that one can have for a dollar a day.”
Obviously the patented drugs also offer many potential benefits, but their cost effectively puts them out of reach for the patients Rogosnitzky wants to help.
“All my work is focused on generic drugs,” he says. “It’s not that I’m against using the expensive drugs, but we are generally trying to help patients who have already exhausted those drugs or cannot afford them. The benefit of generic drugs is first that price is very low, and second, that these drugs have been around for so many years that the safety profile is very well established. So we know what we’re dealing with.”
Rogosnitzky’s MedInsight Research Institute has a well-established track record in this arena. MedInsight doesn’t conduct its owns studies; rather, it has assembled a global network of expert literature analysts it calls upon for various projects. This staff combs through medical journals and distills complex knowledge into simple and actionable summaries. Its work priorities are determined by a combination of factors: areas that offer opportunities for tremendous impacts, such as cancer, or COVID-19; donor interest in particular subjects; and timely topics that are neglected by others for commercial reasons.
“The discoveries of the side benefits of drugs are mostly made by doctors during routine prescriptions,” says Rogosnitzky, “but this priceless information, even once published, remains lost in an ocean of 2.5 million new medical studies published each year.
“Since these drugs are generics, there are no pharma sales reps promoting these uses, and these lifesaving and life-altering opportunities remain lost. MedInsight’s goal is to make impactful treatment opportunities known to patients who have exhausted the accepted treatment options. This is achieved by mining the literature, identifying the published reports of the side benefits of generic drugs, indexing them, distilling the findings into simple language, and educating patients and doctors worldwide about these treatment opportunities.”
One of MedInsight’s early initiatives involved the successful repurposing of naltrexone, an anti-opiate-addiction drug, to treat chronic and autoimmune diseases in very low doses, like Crohn’s disease. The treatment, low dose naltrexone (LDN), had first been discovered at Penn State University in the 1970s, but only saw use when a New York doctor used it to treat his own multiple sclerosis. When he began prescribing it to others, word-of-mouth gave it momentum among patients, and by 2002, there were 2,000 people taking it.
Rogosnitzky initiated a clinical trial of LDN for the treatment of Crohn’s disease in 2002 at Hershey Medical Center, and its success opened the floodgates. Today there are more than 120 other clinical uses for LDN, of which 70 have been trialed, clinically verified, and published by over 100 academic institutions worldwide. Globally, nearly half a million patients are benefiting from this treatment each day.
With 9,000 generic drugs in existence and 45,000 to 50,000 new papers published every week in medical literature — around 2.5 million each year — Moshe Rogosnitzky has his work cut out for him. Extracting specific information for a given drug’s effectiveness against a disease is akin to trying to siphon off water from a high-pressure fire hose with an eyedropper.
“Our problem at the moment in medicine is that we have an overload of information, and we miss the many gems buried in there,” says Rogosnitzky. “Every year, a few thousand such gems are added, because a doctor treating a patient can serendipitously discover a treatment that helps for something other than its intended purpose. And usually, the discovery is made by the patient, not by the doctor. The patient comes back to the doctor and says, ‘You know, this helped me for this particular symptom too.’
“And the doctor says ‘Wow,’ and takes the credit and publishes it. Then it falls into this massive black hole of medical literature. Most doctors have no reason to invest their own time and funds in publishing these reports. And the little that gets published, several thousand papers a year, don’t go anywhere because no one has a commercial interest in disseminating this knowledge or developing the treatment further.”
Artificial intelligence tools are not the solution, maintains Rogosnitzky. “The most sophisticated AI we have can’t do the work,” he says, “because every doctor writes in his own style, and a lot of this literature is not even in English. Furthermore, it costs $40, $50, up to $80 to buy one of those research papers. So you have to actually have a physical team mining through this, reading it, extracting that valuable information, those insights that you need, and then feeding them into a database.”
Rogosnitzky’s research institute, MedInsight, has in fact begun constructing that very database, under a project called Cureiosity — a portmanteau of “cure” and “curiosity.” A team of medical researchers around the world mines the existing medical literature for information on beneficial off-label uses of generic drugs and converts that to a format artificial intelligence tools can extrapolate from.
“Every single disease that we know of, every autoimmune disease, every cancer, has, in my experience, at least 30 or up to 100 or more treatments that have been tried and tested, at some level, with patients, which most of us are completely unaware of.”
Discovering those hidden gems costs a lot of money. MedInsight’s work is funded through donors; but private companies will not invest the time and effort into such an initiative, because there will be no financial windfall at the end. Rogosnitzky’s goal is to proactively gather all the information that’s available and then share all of it with the world, in as open and easily accessible a manner as possible.
“Obviously this is something that has no commercial interest behind it,” he says. But it’s well underway.
A few years ago MedInsight began developing a new system based on a graph database, which gave the researchers new insights into how diseases are related. For example, the graph showed a strong connection between breast cancer and prostate cancer, which medicine has traditionally viewed as mirror opposites of each other; one seems to be exacerbated by estrogen, the other by testosterone. The graph’s data backed up a theory Rogosnitzky had publicized a few years earlier.
“I’d published a book chapter a few years earlier postulating that both these diseases are spurred by estrogen and not by testosterone,” he says. “And since then, some of the biggest cancer centers — MD Anderson, Sloan Kettering — had begun trials treating prostate cancer with testosterone, which went against what everyone had been thinking for the last 70 to 80 years. But I’d reached that conclusion from a completely different approach.
“So then we suddenly saw this correlation in the graph database, and we said, ‘Wow.’ This is the evidence that we have to change our thinking over here.”
Of course, making all this information available already presumes there will be an interested audience. And in Moshe Rogosnitzky’s experience, that is not necessarily a given among today’s medical practitioners.
“We called this project Cureiosity because what I have found, in dealing with doctors, is that the number one factor in determining whether a doctor is able to help his patients is whether he’s curious,” he says. “If a doctor doesn’t want to learn, he won’t hear about anything new.
“I remember once seeing a sign in London on a wall somewhere that said, ‘A degree never hurt someone who was willing to learn after getting one.’ And what you often find with doctors, or with anyone who’s been through the secular academic system, is that they already feel accomplished, once they’ve learned what they’ve learned. A continuing thirst for knowledge, wanting to know more, curiosity, is the most important factor for a good physician.”
Moshe relates an interesting teshuvah from his grandfather, the posek Rav Mordechai Dov Rogosnitzky, on trusting doctors. Halachically, he says, the concept of trustworthiness of non-Jewish doctors derives from a paradigm in kashrus concerning whether a non-Jewish chef can be believed if he states a certain mixture possesses a definitive amount of meat or dairy. Just as the non-Jewish chef will not damage his professional reputation by knowingly giving a wrong answer, so the same motivation will apply for the doctor, and he is also presumed to be trustworthy.
“My grandfather said that chazakah only applies up to a certain point,” says Moshe. “When a doctor becomes too great an expert, then he loses that chazakah. Because if he’s seen as that strong an authority, then he knows no one’s going to argue with him. It’s very applicable, because people often make this mistake of wanting to go to the biggest expert, the head of the department — and in many, many cases, it’s a fundamental mistake.”
He says that doctors themselves are aware of this dynamic. A Washington lawyer called Moshe seeking his advice; her father, himself a doctor, had a brain tumor. “I asked her where her father was, and she said he worked at particular US hospital. So I immediately guessed he must be treated by this doctor at that same hospital who was considered the ‘Kohein Gadol’ for that type of cancer. But she said, ‘You know, my father is a physician. He’ll never go to the head of a department. Never!’ ”
Rogosnitzky says he wishes more people in the Jewish community would bear this in mind.
“We have a problem, particularly in the Jewish community, and more so in the frum community — the frummer people are, or perhaps, the less exposure they have to a non-Torah education, to secular studies, the more respect they have for people with titles,” he laments.
Rogosnitzky says that for years he wondered why frum Jews harbored such respect for titles. He discussed the problem with rabbanim and rebbes often and never got an answer that satisfied him. Then, he says, he spoke about it on a Shabbos in Lakewood with Rav Yosef Dovid Neuschloss ztz”l, who told him, “I’ll explain to you what’s going on.
“People are afraid of the responsibility of making a wrong decision. They know if they follow whatever the doctor says, even though the odds are they won’t survive, that’s the doctor’s achrayus. But if chas v’shalom they themselves decide on something that fails in the end, they fear that they’ll have to give a din v’cheshbon in Shamayim.”
Rogosnitzky admits he didn’t quite buy that explanation. Then a couple of days later he visited Johns Hopkins Medical Center, where he was asked to see a patient who had a renal carcinoma, a type of kidney cancer. This patient was an Iraqi-born architect and a brilliant man. He’d researched his own disease thoroughly, and it took an hour for him to recount to Rogosnitzky all the doctors he’d seen in the US, including the head of the NIH cancer division. In the end, they all told him, “You know more about this than we do. We can’t tell you what to do.” Now this architect was turning to Rogosnitzky.
What more could Rogosnitzky offer him? Well, he explained, “What I’d like from you is, perhaps you know an expert somewhere who knows a little bit more than me, and he can tell me what to do.’
“I don’t understand,” Moshe told him. “All these experts have told you that you know more than they do. Why don’t you take the responsibility and make your own decision?’
He gave a sad smile and said, “If only you realized how difficult it is to take that responsibility.”
Then the words of Rav Neuschloss hit home.
Part of a patient’s taking responsibility is choosing the right doctor, Rogosnitzky says. And the right doctor is one who will work collaboratively with the patient to arrive at treatment decisions. Seeing themselves as partners, not bosses, requires humility on the doctors’ part.
“True, doctors are limited on time,” Rogosnitzky says, “and they may not have the answers. But at least they should not dismiss patients’ questions. If a doctor’s not willing to admit that he doesn’t have all the answers, and he dismisses the patient’s questions, that’s a doctor whom I personally believe one should run a thousand miles away from.”
Rogosnitzky once referred a patient to a specific doctor. But the patient objected, saying this doctor had admitted making mistakes.
Rogosnitzky responded, “That’s exactly why you should go to him! All doctors make mistakes. They’re all human. But the ones who don’t admit it are the dangerous ones.”
He describes a pediatric liver cancer case that he was involved in two decades ago as an apt exemplar. A baby born in Israel had been diagnosed in utero with an extremely rare form of liver cancer. Doctors started chemotherapy on her when she was eight days old, but the baby almost died of septicemia after the first round of treatment. The parents were appalled.
“They decided to just run away from the hospital,” Rogosnitzky says. “Somehow they got to me.”
Though all the doctors in Israel said the cancer was inoperable, Rogosnitzky managed to locate a doctor in New York who said he could operate. “He was the only one in the world to say that,” Moshe says. “And the doctors in Israel refused to allow us to fly the baby to the US.”
He points out that dealing with pediatric patients is extremely complex, because in most countries, if the parents go against the doctor’s advice, then the state can take custody of their children. In this case, three major Israeli hospitals sent representatives to court to support removing custody from the parents.
“But miraculously, in a precedent that hasn’t been repeated since, the judge agreed with us,” Moshe says. “The baby flew to New York, had the surgery successfully, and there was residual disease. Afterward, we used one of these treatments that I’d researched at Penn State University. An unapproved drug — and it still is an unapproved drug. Essentially, it’s an endorphin, a feel-good hormone the body produces itself, given in injectable form. They were studying it for pancreatic cancer. And we used that in combination with one or two other therapies.
“That baby is now 19 or 20 years old and doing very well. A few years after that, another case followed, and she’s also cured, and we reported those cases in the medical literature.”
None of this would have happened, he notes, had the girl’s parents just knuckled under to their doctors’ wishes.
“I think that taking responsibility is one of the most necessary aspects when it comes to making health decisions,” Moshe says. “But it’s very, very difficult for people to take responsibility for those decisions.
“In the case of that pediatric cancer, the parents took responsibility, fought the system, and succeeded. Obviously, one has to be emotionally built to take that responsibility. I think it was Dayan Abramsky ztz”l who asked, why, when people go to see a doctor, they make so many inquiries about his background and track record. But when they get onto a plane, they don’t check the credentials or experience of the pilot. And he said, because they and the pilot are on the same flight. And we have to realize that in medicine, the doctor and the patient are not on the same flight. That may trigger people to take more responsibility.”
Rogosnitzky envisions a future for medicine that places patients at the center, realigning physicians, researchers, and pharma companies around the patient, unlike the current model.
“It’s essentially placing health ahead of wealth,” he says.
He cites MedInsight’s success with its LDNscience initiative as a model: a patient-driven repurposing of a generic drug to treat a chronic disease. With the Cureiosity project goal of cataloguing the world’s 9,000 other generic drugs, that success could be repeated many times over.
“There needs to be a concerted effort in that direction,” he says. “Last year I lectured about the LDN project at MIT. Here you have a single drug, over a period of ten years of public education, impacting the lives of half a million people and saving their economies at least $5.5 billion in costs of reduced hospitalizations and disability, and probably a lot more. Imagine if you replicate that across dozens of drugs. What’s the potential of turning around the way medicine is practiced?”
As they did with their patients pushing for LDN treatment, says Rogosnitzky, doctors will learn to appreciate collaborative decision-making and patient activism. Asked if doctors might not put up a fight against this kind of reform, he proclaims that he is not fearful.
“Because I’m degree-less, there’s nothing you can take away from me,” he says. “Someone who’s within the system is always afraid what their colleagues will say. Baruch Hashem, I don’t have that fear. Yes, I’ve learned to fine-tune my messaging over the years, talk more tactfully, study a doctor’s publications before visiting with him so we can talk on level ground. Absolutely, not having to fear that antagonism or resistance is definitely a major bonus of my not having taken a formal medical education.”
Rogosnitzky has found an unlikely ally in this movement — Dr. Alejandro Jadad (pronounced “Haddad”) of the University of Toronto, inventor of the Jadad Scale, the first validated tool for assessing the methodological quality of clinical trials and one of the founders of evidence-based medicine, which is essentially the whole modern-day medical philosophy.
“Dr. Jadad spent much of his career fighting for evidence-based medicine, which means, look at statistics, don’t trust your own judgment,” says Rogosnitzky. “And in recent years, he’s made a complete turnaround to his approach.”
When Rogosnitzky met Jadad in Toronto about eight years ago, he’d established a project called, curiously, the Maimonides Project. Its objective was to build medical schools with a completely different approach, enabling independent thinking.
When Rogosnitzky asked Jadad why he’d named the project after the Rambam, Jadad replied, “Because Maimonides says, ‘Teach thy tongue to say “I do not know,” and thou shalt progress.’ ”
Rogosnitzky challenged Jadad, noting that the quote first appears in the Talmud (“Lamed leshoncha lomar eini yodeia,” Berachos 4a).
Jadad retorted: “I know, it’s in the first tractate of the Talmud, on page 4. But there it does not end with the words, ‘and thou shalt progress.’ And that is why I named it after Maimonides.”
Jadad introduced Rogosnitzky to a thymic cancer patient, a 70-year-old California lawyer who had failed three types of chemotherapy and was expected to live two more weeks.
“Jadad threw the case at me and said, ‘Show me what you can do with all your ideas about repurposing off-label drugs.’ ”
Rogosnitzky set to work, developing both a diagnostic and an immediate therapeutic intervention plan for the patient. He had to fight for a Dota-Tate scan, which no one thought was warranted. But Moshe prevailed, they did the scan, and it came out positive. Within hours, the FDA had granted special permission to use a drug not approved for this type of cancer.
“The patient was flown to Texas and underwent treatment with that drug, in addition to the other treatments that I proposed for him, and he went into complete remission,” recalls Moshe. “And he lived another five years.”
Jadad later said this was an eye-opener for him — “the invisible became visible.” He joined forces with Rogosnitzky and is now a partner and supporter.
Moshe Rogosnitzky engages in this enterprise without regard for what kind of people he is helping. He helps patients of all sorts, and the majority of the doctors he interacts with are not Jewish. Yet he has clearly not lowered his religious standards, and he peppers his speech with words from Chazal and poskim. That is because for him, it is all part of a greater whole.
“We have an obligation to worry about the world,” he says. “In the Beis Hamikdash on Succos, we brought korbanos for the nations. So you see, HaKadosh Baruch Hu has put a certain achrayus on us Jews for what goes on in the world. And we can’t look on this in an insular fashion. We have to look at our ability to impact the world. The Netziv, in the single-page introduction to his monumental work Ha’amek Davar, explains that this was the heritage of the Avos.
“Because of anti-Semitism, because of the Holocaust, we’ve become very insular in our approach. But we bear a great responsibility. We have to do what we can to help the world at large, and that will undoubtedly trickle down and help frum Yidden in the process.”
(Originally featured in Mishpacha, Issue 837)
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