Growing “Mini Brains” to treat neurological diseases with Margaret Magdesian

November 7, 2019

As a biochemist and pharmacologist, Margaret Magdesian dedicated her career to studying the nervous system. After realizing that drug testing is performed on animals that do not have the same diseases as humans, she founded Ananda Devices which has developed a new way of growing a human nervous system on a chip so that medication can be tested directly on patient-derived cells.

“Today, 20% of the world’s population suffer from neurological diseases. This is something that affects, especially women because women live longer. “

In this episode:

  • How medication for human diseases are tested on animals
  • Why the failure rate for medications to treat neurological diseases is almost 99%
  • How Ananda produces “mini brains” that can be used to test on patient-derived cells
  • Ananda’s open-source approach to science and patient data
  • Margaret’s journey from academic to entrepreneur

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Show Notes

Transcript

Margaret M: We’re not replacing animals from one day to the next, it’s not going to happen. Our technology came out completely with replace, but it’s a spec process and when you have 99% failure, and if our technology bring 5% hope, it’s already much better than what’s in the market.

Vicki Saunders: Welcome to SheEO.World, a podcast about redesigning the world. I’m your host, Vicki Saunders. In each episode you’ll hear from SheEO venture founders, women who are working on the world’s to do list. These innovative business leaders are solving some of the major challenges of our times. Sit back and prepare to be inspired.

Margaret M: My name is Margaret Mathnasium. I’m the CEO and founder, of Another Devices. I’m a biochemist and a pharmacologist and I’ve spent most of my life trying to accelerate drug development and three years ago I launched a startup company. And our goal is to produce human organs on a chip, so we produce mini brains, mini spinal cord, in innervated tissue to accelerate drug testing and reduce toxicity of most of the compounds in the market today.

Vicki Saunders: Okay, so I have a million questions about that. Thank you, Margaret, for joining us.

Vicki Saunders: What do you mean human organs on a chip? What does that actually enable us to do? And tell me how you’ve got to that space.

Margaret M: Yeah, so I was always intrigued, why couldn’t we launch medication faster in the market for there are so many patients at the hospital, especially patients with neurological diseases, and when we say neurological diseases, this is really broad.

Margaret M: We can talk about autism, Parkinson’s, Alzheimer’s, but also chronic pain such as migraine or back pain. You know, we do not have any medication that efficiently attack the diseases in our nervous system in general. So I’ve dedicated a lot of of my life, a lot of my career in studying the nervous system. And I realized the nature problem is that every drug is tested in animals. But animals usually do not have the same diseases as humans. Animals do not have autism, do not have Multiple Sclerosis, do not have Parkinson’s. So we test the medication for a disease in a model that does not exist. The best approach would be to test in humans, but we cannot do that. So we develop a new way of growing human nervous system, mini brains, mini organoids on a chip so that people can test their new medication directly on patients, the right cells.

Vicki Saunders: So let me just ask the obvious question from an outsider who knows nothing about this space. So why do we continue to test our medication and a potential, you know, breakthrough discovery on animals when it’s not working?

Margaret M: Yeah, so it’s not everything that is not working. Like for cancer research, animals have cancer as well. So about 40% of the drugs we test in animals reproduce the same results in humans. And that’s why cancer has advanced so much and today there’s cure for multiple types of cancer. However, for neurological diseases, that failure rate is almost 99%. I have cured Alzheimer’s in animals, five hundred times but never in humans. It’s still, we cannot launch a drug in the market without testing and some living organism, you have to test in something that otherwise could be very damaging.

Margaret M: There’s this famous case of the Thalidomide, which was an antidepressant in the 70s and they launched in a market and then a lot of babies were born without arms and legs. It seemed that it was not toxic at the beginning. Then since then, all the regulatory agencies have imposed a lot of testing in animals before launching anything to the market.

Vicki Saunders: Obviously, as you said before, you can’t biopsy the brain or the spinal cord. How did you come up with this idea to do that? How did that become a possibility to put them on a chip to be able to test?

Margaret M: Yes. Another factor that really hinder advances in neurological diseases is that we cannot take a biopsy from the brain and put under the microscope. While everyone is willing to give a biopsy of their tumors and we can put into microscope, we can add drugs and can see how it’s working about the brain, the spinal cord. No one wants to cut a piece, it’s completely damaging.

Margaret M: The recent advances in STEM cell technologies have shown that we can, today they could blood from the patient, we add a cocktail of drugs and we’ve transformed the blood into nerve cells. And then we put them on a plate and we grow sort of a flat brain, but this is not the same organization as our natural brain and it doesn’t respond properly. So, that’s where another devices come in. Our company basically, we’ve produced some micro moats, some scaffolds made of medical silicone and then we take the cells| from the patients and then we transformed them in 3D structures and really they really look like mini brains, they’re about half a centimeter in size.

Vicki Saunders: Wow. And is this something that can scale up so that everybody could move from testing on animals to testing in your structures?

Margaret M: Yes. Even to scale up the technology was a challenge. We worked with the Canadian National Research Council for about two years, scaling up to make sure that we could produce as many scaffolds, as many micro silicone devices so that everyone could use. We have a partnership was the Montreal Neurological Hospital and then we can use directly, patient derived cells and the patients are willing and they know what we’re doing and they’re very happy to help in the development of new medications for their diseases.

Vicki Saunders: Right there, you sort of touched on another thing I have, which I imagine it’s to do with privacy of people’s DNA, of their cells in the medical assistant. Can you tell us a little bit about how that works right now and what you’d like to see?

Margaret M: The market today’s a lot about selling patients’ data. A lot of people with, as we heard from Facebook or you know, it’s the most common case, but any gadget we have, our cell phones, everything, is recording and the Fitbits and all this data and we never know where it’s going. Even people that participate, sometimes in clinical trials they say, “I gave blood to a lot of clinical trials and I never heard back what happened”. The good thing about the neurological hospitals have open science platforms so the patients are informed from the beginning to the end what’s happening and everything would discover, all information we gather with their cells is open to the patients and to the public in general.

Vicki Saunders: Which is a whole new way of thinking about privacy and data, right? When you’re in an open platform and it gets used across and then are you then giving your permission for it to be used in a certain way and therefore not in other ways or how does that work?

Margaret M: Yeah, that’s a completely open science, so everything’s open and that to the public apart from the weak patent hours plates, the scaffolds we develop that’s back and that’s our property and that’s what we sell, but all the data people acquire with it and everything that comes from the patient and goes back to the patient is open to the public and the patients has completely access to is there are different from other models and from other companies that are hiding the data or selling the data. We heard about this company, I think it was 23 And Me, everyone paid to get their DNA sequenced and they just sold all the DNA to these people, to GlaxoSmithKline from a surgical company. So nobody knows where their data is, what they’re doing with it. And that’s what we’re trying to avoid. We are very transparent and our goal is really to work with the patients to get the best results for the patients.

Vicki Saunders: So as we’re testing drugs in the world today to see how to get them to market and we have a very strong regulatory structure, how does that actually work versus what you are trying to do? What in the process that you’re creating? Right now we’re using animals and so how many animals do you use to in a year? What does that actually look like? Tell us a little bit about the system so we can understand how you’re shifting it.

Margaret M: Yeah, we’re talking about a lot about drug development, but anything that comes in contact with humans. It could be a medication, cosmetics, could also be pesticides or any chemical that comes in contact with our skin or with our body has to be tested first in animals for toxicity and there are regulatory agencies making sure that nothing toxic comes to the market. And the use of animals today is about a hundred million, is estimated in a 100 million animals to test the toxicity of everything, all the new products that comes to market.

Vicki Saunders: Is that each year?

Margaret M: Each year. More than a hundred million animals. Yes.

Vicki Saunders: Wow. There’s a trend, I’ve wrote about, that people are trying to outlaw that.

Margaret M: Exactly. So 67 countries today have banned the use of animals for cosmetics and other applications. For pharmaceutical use it’s hard to, because, certain drugs that we need to develop, we have no option but to test in animals. But that’s changing now with our technology, there are other four companies doing organ on a chip as well, more related to heart or kidney or other organs. To the best of my knowledge, we’re doing the only one doing nervous system and now they’re trying to change it. The regulators are imposing legislation to make sure that people reduce, refine and replace animal testing for technologies that are more animal friendly and in human friendly at the end. Right, because we’ll get better, more predictive results with human tissue and this market is growing about 70% a year.

Vicki Saunders: Wow, that’s amazing. How big of a problem are neurological diseases at this moment?

Margaret M: Today 20% of the world’s population suffer from neurological diseases. This is something that affects, especially women because women live longer. This is really sad because women live longer, they are the majority of the caregivers as well. They take care of the patients and no wonder depression and anxiety affects women really hard. Parkinson’s, especially Alzheimer’s and Multiple Sclerosis in women also have a much higher incidence and we have no cure and we don’t even understand how the female brain works because over 75% of all the tests today are performed in male subjects. So any drug that is in the market was first tested in a male rat, so no wonder when people say, I don’t know what’s in your head, they really don’t.

Vicki Saunders: This whole, I mean honestly as I talked to each of our grantors as we’re going through these podcasts and learning about the systems that they’re disrupting and shifting and coming up with new solutions for, it’s amazing how women are left out of a lot of like every single aspect of society, right? But 75% of all tests, is that shifting? Have you seen movement in that area in the last few years or not really?

Margaret M: People were trying and I think our technology is really what’s going to change. We are disrupting this whole system. Now we’re working with the hospital and they have already defined several lines of patient cells. So first we take the blood from the patients and then we have to make sure that the patient really has Parkinson’s. So there’s a lot of genetic tests, clinical tests that we put out together. And just by doing this full trial, we have very specific cells from male and female brains. And this is amazing. So it’s the first time we’re growing your mini brain of a woman on a chip. And for the first time we’re going to test the drug directly on them and see what’s the response. This is marvelous and I’m so grateful to be part of this change and we need that.

Vicki Saunders: That’s just incredible. And so I would presume that with an aging population, as we move older and older, so in certain markets around the world, Japan in particular, you start to think about that market with aging demographics. Presumably, the neurological diseases will grow and that 20% will rise. Are there predictions around that?

Margaret M: Yeah, so this is horrible to hear, but after 80 years old, about half of the population will develop Alzheimer’s disease. So with the rates increase from 60 on, but after 80, 50% have Alzheimer’s. The more we live the more chances of dementia, of course. And the other scary data is that a lot of babies are born today was autism and those rates are increasing exponentially, like two years ago, it was one in 69 kids were born with autism. Today, it’s one in 57.

Vicki Saunders: Wow.

Margaret M: In just two years and it increased that much. We don’t know really how it starts. Apparently, it’s a syndrome, there could be some genetic factors, the environment, people don’t know where it’s coming from. This is more than time that we start to use human data to understand what’s happening. Otherwise, we are driving into an age of demented population.

Vicki Saunders: Wow, that’s unbelievable. What are the biggest challenges you are facing getting your work out into the world so that we can solve for these diseases and thank you very much for doing what you’re doing because, Oh my gosh, do we ever need it?

Margaret M: Yeah. I’ve worked most of my life in academia so we’re always pushing through innovation and we are always eager to for new solutions. When I jumped into entrepreneurship I said, “I have to bring this to the market, everyone has to hear about it and let’s change it”. But it’s not that easy to change. And that’s when I realized I had a disruptive technology.

Margaret M: When you go talk to someone, to a large corporation and they say, “but we have always used animals”, there’s a lot of jobs involved in this. There’s a whole system. There’s a whole the process of drug development that depends on, and then I tell them, “but you know on the other hand you’re buying a new drug for billions of dollars. Millions here, billions there and you don’t even know it’s going to work. You have to test in a better system. We have to change everything from, from the beginning”. It’s crazy. But seems like it’s easier for pharmaceutical companies to buy new drugs in the market who listened to that every day companies buying another drug or is developing another drug, is investing billions of dollars but not in the basic principle, which is the testing.

Vicki Saunders: Which is a huge challenge, right? The inertia of the way things are really slows down innovation all the time. And are you noticing in some parts in the Science ecosystem that are moving faster than others or is it similar across all of the different groups?

Margaret M: No, it was a big surprise. When I launched the technology, I expected all the pharmaceutical companies to come and immediately adopted it. But the first to come where the cosmetic companies, because they are feeling the pressure from the population, they have this pressure to stop animals and they are looking for anything. I was surprised I had a contract with L’Oreal, I was surprised by the amount of scientists and the amount of people really involved in changing the market in moving out of animals. But it’s because they have the pressure. Pharma companies do not have the same pressure on them to change.

Vicki Saunders: cause we don’t understand what they’re actually doing behind closed doors I guess, right? Was it really in the 80s body shop and Anita Roddick really pushing this anti animal testing thing, or that’s what I saw anyway in the press. So that automatic pressure from the customer really works, but it’s must be very hard to make that happen in a pharmaceutical space.

Margaret M: It is. And it doesn’t mean necessarily, we’re not replacing animals from one day to the next. It’s not going to happen. Our technology came out completely replace, but it’s a spec process. And when you have 99% failure, then if our technology bring 5% hope, it’s already much better than what’s in the market.

Vicki Saunders: Yeah. So what do you wish was true in your day to day work that would make everything so much easier? What would change?

Margaret M: Yeah, I wish it would be easier for people to jump into new technologies. Because when we’re talking to large corporations is like we’re talking to, it’s not even a country. Recently they asked me, “Oh what’s your largest market?” I said, “I don’t know” because I talked to a large corporation in France, but then their labs are in India or in a completely different country, the contracts are with the US, this companies or countries themselves and it’s very hard to move. So I believe if the decision making would be faster, we wouldn’t be here.

Vicki Saunders: It’s interesting because I think this is, this is a challenge of globalization, right? So you bring all these companies together, they start to get bigger and bigger, but there it’s very complex or across all kinds of different regulatory markets, the supply chain starts to get really crazy and it was just so much easier when things were smaller and in local environments so that we could move faster. Ironically. Right? You use, you would think that by aggregating everything together we could move faster, but it in fact sort of slows down decision making.

Margaret M: No, we’re negotiating contracts now with different corporations and most of them is whatever, any increment, I have to hear, “oh, in the next global meeting, I’ll bring this up”, in the next global meetings when they put all their headquarters, get in, Oh my God, I’ll take another month.

Vicki Saunders: You said that you were an academic. We know that this is one of the big challenges in a lot of markets where we have academics coming up with incredible ideas and then to commercialize them is really a hard part. So what made you step out into entrepreneurship from the lab as an academic? That must’ve been a pretty big and kind of scary decision to make.

Margaret M: It was, I think it was the scariest decision I’ve made, even scarier than moving to Canada. But the issue was, as I said, my mission always to accelerate drug development. And then when I saw the devices I was producing were being used by different labs. At the beginning I was just running a facility at Miguel and developing this devices for other researchers inside the university. And one day they sent me all the pictures of how my devices have helped them in their research. So then I saw they were using my devices to accelerate researching Parkinson, in Alzheimer’s, in Multiple Sclerosis, in cancer. And I said, “wait a minute, should it continue, here in the lab, just giving one device to everyone and selling just internally or should I go to pharma, scale this up and really make an impact, accelerate drug development for everyone”. And I thought this would be a much more impactful decision. That’s when I moved, resigned from my position and I jumped.

Vicki Saunders: Wow. You have family? I can imagine coming home like I think I’m going to start a business. I mean, I know personally I never thought I’d be an entrepreneur, but kind of jumping into that, you’re surrounded by people who are like, are you crazy? What are you doing? What do you know about running a business? Did you have an immediate support from your family? Or what did it feel like?

Margaret M: Yeah, it took really six months to to make this decision. So it was there from the “Aha” moment to really quit everything. It took me like six months, but my family was very supportive. I remember that the last day in the lab I was so, so afraid. I was like, Oh my God! Or maybe I will never come back to a lab again. So, and I just called my husband like can you pick me up? I don’t think I can take the Metro now. My husband and my two kids, they are also believers in what I do. They’re also more or less in science, my daughter is now a psychologist, and she’s a volunteer at the hospital, with demented patients.

Vicki Saunders: Wow.

Margaret M: Has been working for four years with them. When you see the reality of people everyday, you have a different perspective.

Vicki Saunders: Yeah. This is something that we talk about a lot, which is when you’re shoulder to shoulder, suffering with people that are going through this, you just have such deep insight into the challenge and it helps you to create better solutions for them, as opposed to someone who sort of outside looking for a market opportunity. It’s just a very different motivation that drives your creation.

Margaret M: Yeah, and someone must speak up for them. Someone mus show what it is because in our world today, you know where people were unhappy because they don’t have a certain pair of shoes or unhappy because, such a silly things. We have to realize sometimes, which are the real values of life. Right.

Vicki Saunders: This is very true. Thank you very much for all you’re doing in this space. Do you have an ask? This is going out around the world, not just in North America, and wondering if there’s something that you would like people to leave this podcast thinking about.

Margaret M: I would like to ask everyone there. So to make this dream happen, to help all the patients to accelerate with development. We need funds. We’re looking for investment now. Do you know any investors that would like to join? Please send them our way. Or if you know of any firm: surgical, cosmetic, pesticide companies that want to make less toxic products and want to try animal free solutions, please send them our way as well.

Vicki Saunders: Great. Well, thank you very much, Margaret, for your time and please get back to work, so you can help solve these for all of us. I can’t believe that as we live longer and longer, that literally 50% of us will need solutions that you’re helping to create right now. So thank you very much.

Margaret M: Thank you. It was a pleasure. Thank you all.

Vicki Saunders: Thank you for listening to the SheEO.world podcast. If this conversation resonated with you, please share it with a friend and subscribe on your favorite podcast player. If you’d like more information about SheEO, please visit us at sheeo.dot world. That’s S H E E O, dot world.

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