Before their son was born, Sanath Kumar Ramesh and his wife Ramya had normal first-time-parent jitters. Ramesh, who works for Amazon as a software engineering manager, was so excited to welcome his little boy. He was ready for the challenges and rewards of parenthood.
In August 2018, Raghav was born, and Ramesh’s life began changing in ways he’d never expected.
On this episode of GeekWire’s Health Tech Podcast, we’re reconnecting with Ramesh to hear more of his compelling, inspiring story. We previously reported on Ramesh and Raghav’s doctors and their efforts to treat Raghav. In this podcast we go deeper into Ramesh’s experience as both a father and a talented tech engineer working to help both his son and others struggling to save loved ones battling rare diseases.
Listen to the episode below, subscribe to GeekWire’s Health Tech podcast wherever you listen, and continue reading for an edited transcript.
Ramesh: Everything was smooth through pregnancy and everything up until Raghav was born was perfectly smooth. When he was born, he was so tiny, so precious. I remember holding him in my hands and thinking that my life has changed. My life has changed not because something bad happened, but because I have a purpose now. And the purpose is this baby. And we were super happy for the first three or four hours after birth until a doctor came to us and said, “There is something wrong with Raghav.”
She didn’t quite understand what was going on at that time. But she said, “There’s something wrong with Raghav. He does not look like a typical child. We believe there is something that’s fundamentally going wrong with him to a point where he could have a lifelong illness, that Raghav might actually have a neurological problem. I had no idea what a neurological problem meant. We thought it something that you give a pill and get it done with.
We spent the next 21 days in the hospital trying to figure out what was wrong with him. But we still came back home without an answer. And after we came back home, we were hoping this was just the trauma of the birth, this was just something that was one off, and this would go away over time.
Lisa Stiffler, GeekWire: As Ramesh was to learn, Raghav faced bigger struggles than he ever would have imagined. But rather than despair, Ramesh unleashed his problem-solving, engineering nature to tackle the problem — carving a path of hope for his family, and for many others confronting similar situations.
Early photos of Raghav capture a bright-eyed, smiling little baby with long eyelashes and black hair. He’s adorable. And during his first year, Sanath and Ramya tried so hard to help their son grow and develop like a typical child. But he just couldn’t do the things that a normal baby could. He needed a feeding tube to eat. When he got his first teeth — an exciting developmental milestone — he bit his tongue and lips. Raghav lacked the motor skills needed to control his movements.
Month after month, Ramesh didn’t know what was wrong with Raghav. When his son’s first birthday came, the family was ready to set aside their difficulties and celebrate at a park in Bellevue, just east of Seattle. It was a beautiful, sunny Northwest summer afternoon.
Ramesh: As I was getting ready to cut the cake, I got a call from Raghav’s doctor and she said, “Oh, by the way, we found out what’s wrong with Raghav. We found out his problem. He has this genetic condition due to a mutation in a gene called GPX4.”
And I was super happy in that instant. And I said to her, “Oh, this is awesome. OK, we’ll come next week to get medications for him.” And she said, “Hang on, there is no medication for this disease. And in fact, we believe Raghav might be the only kid alive with this condition. Because all the kids with this disease passed away a few weeks after birth.”
You know, here I am standing there getting ready to cut the cake, and someone is telling me that my son is lucky to be alive today. And that’s the moment that transformed everything about about my life. I thought my life was transformed when my son was born. It was transformed again, on his first birthday.
LS: It’s excruciating to imagine hearing this news. To think of how you would process this new reality. Researchers estimate there are more than 6,000 different rare diseases, including the one that afflicts Raghav. An estimated 263 million people worldwide have unusual conditions, many of which are chronic or fatal, and most affect children. Given their rarities, almost none have treatments available.
For Ramesh, this was a call to action.
Ramesh: I’m a software engineer by training. And the one thing that is drilled into my head is that I have to solve problems. And at that point in my life I was getting really, really excited by really hard problems. And I thought the hardest problems to solve were debugging a piece of software.
When I was presented with this problem, which is my son has a genetic disease, I thought of this as a problem I needed to solve. I started Googling about this disease and I couldn’t even spell it at that point. I started Googling about this gene. And I first needed to know what a gene was in the first place. I knew there are things called genes, but I don’t know why the hell they are in my body. And it took me a little bit of searching to realize that there is basically nothing about this disease in the literature.
LS: The condition that affects Raghav is extremely rare and it’s a mouthful: Sedaghatian type Spondylometaphyseal Dysplasia. It’s so rare, that it didn’t yet have an acronym, so Ramesh gave it one: SSMD.
The condition causes cardiac arrhythmia, and skeletal and central nervous system abnormalities. SSMD is the result of a genetic mutation that sends oxygen free-radicals and iron running amok inside of cells, killing them.
One of Raghav’s doctors at Seattle Children’s Hospital, Dr. Russ Saneto, said that he knows of four other cases in the world: two kids in San Diego, one in Japan and another child in Belgium who died.
But there were other researchers who worked on the gene, called GPX4, so Ramesh reached out to them.
Ramesh: There was a lot of information about the gene, people were talking about it rom a cancer perspective, from an aging perspective. There was even a very recent, very new biological pathway that was invented on top of this gene that people were really excited about. So I quickly found all of latest publishers on this topic and started reaching out to them, and put together a very small team of researchers and technicians that could hopefully work with me.
And then I also realized that given the severity of this disease, finding a new treatment is not going to be possible. Because during my search, I realized that building new therapies are 8 to 10 years of work, and cost billions of dollars that a biotech company would invest in. And I don’t have the time and I don’t have the money.
LS: But Ramesh was smart and he was resourceful. And his son needed help now. So given that a breakthrough treatment wasn’t right around the corner, he thought about what was, which is the local pharmacy.
Ramesh wondered if there were existing medicines that could help Raghav. Something off the shelf, right now. Working with his son’s doctors at Seattle Children’s Hospital, they came up with 36 drugs that might be repurposed for Raghav’s condition, and settled on a cocktail of four.
Within a month of learning his son’s diagnosis, Ramesh had come up with a treatment, which includes vitamin E and other antioxidants.
And the doctors were able to successfully petition the FDA to let them use another drug that a pharmaceutical company was developing for a different disease. The approach appears to have helped, stabilizing Raghav’s fragile health. But it’s not a permanent solution.
Ramesh: The more long term treatment for these conditions are using a technology called gene replacement therapy. The idea is very straightforward. My son has a mutation in this gene called GPX4. And a mutation is, in software terms, a bug. There are there are several characters that encode this gene, and one of his characters is misspelled.
The gene replacement therapy idea is that you replace the faulty gene with a good one. Sounds straightforward, right? But unfortunately, it is not that straightforward. There are a lot of processes that you have to follow. It’s pretty complex. And it costs $5 to 7 million to build a treatment for my son. And it still takes a lot more money to do a clinical trial to get the FDA approval and make the drug available for the larger population around the world.
My son’s condition has, at this point, only nine patients worldwide, so it’s super, ultra rare. At this scale, we are not going to get a commercial approval from the FDA at all, which is fine, we’ll just keep treating the patients under an experimental setting as much as we can.
LS: Ramesh is not alone in searching for a therapy for a family member’s rare disease. There are numerous foundations created on behalf of loved ones suffering from unusual ailments. The organizations raise what resources they can, and try to recruit experts to help them develop gene therapy treatments. It’s expensive and in some ways the risks could not be higher — you’re literally trying to improve or save the life of someone you hold dear. The stakes weighed on Ramesh.
Ramesh: When I started with my son’s gene therapy, I started thinking, well, I can do a lot of work, I can spend 24 hours nonstop working for 365 days. But what if I fail? What if the people that are with me fail? And so I started asking other patients and patient foundations about their experience building gene therapies, to learn about their successes, but more importantly, their failures.
What I came to realize is a lot of patient foundations fail and struggle and make mistakes. They have to reset multiple times. They have raised multiple millions of dollars to get to a treatment. When that eventually happens, like 10 or 20 years from when they started, their kids are probably not going to be benefiting from it. Either they’re too old to participate in trials, or they’re too sick. And that is not a happy outcome for me. And so I really needed to hedge against this risk of me failing because of myself.
LS: That led Ramesh to employ a very techie idea: open-source engineering. As he was building a team and searching for a cure for his son, Ramesh decided that he would bring along others who are on parallel journeys.
He is now the founder and CEO of OpenTreatments Foundation, a nonprofit that recently launched an open-source platform called OpenTreatments. The platform is a playbook and collection of resources for foundations and people who are also on the quest for rare disease treatments.
There are four rare diseases currently running as pilot projects on OpenTreatments, including the one afflicting Raghav. Ramesh and a team of volunteers built the platform through a collaboration named RareCamp.
Ramesh: I ended up identifying a mechanism where I can help not only my son’s gene therapy, but also help a lot of other families. And just being a software developer obsessed with scale, which is what we do at work, I wanted to not help one or two families, I wanted to be able to help hundreds of thousands of families. I feel like eventually we should be able to have millions of patients that are driving research. That’s the North Star of OpenTreatments. That’s how I stumbled upon thinking about building a software platform.
OpenTreatments provides a clear roadmap to patient foundations to build the treatments. We connect them with the right people who are necessary to advance their programs. And we connect them with the right scientific infrastructure necessary for them to advance research activities. And hopefully, we should also be able to attract funding to help the patient foundations move forward. This is how OpenTreatments was born out of me hedging my own risk.
LS: Work is underway to help Raghav. Ramesh has assembled a team of experts from universities around the world. They’re studying the GPX4 gene and the biology of SSMD. They’re pushing toward that ultimate goal of creating a gene therapy, but it could take three years or more to get there.
In the meantime, Ramesh’s wife keeps working to raise money for the effort. So far they’ve raised about $5 million dollars. They’re also working with Raghav’s doctors to get FDA permission to use a second experimental drug.
Part of the idea of OpenTreatments is that each foundation does its own fundraising, and pursues the genetic and disease research for each unique, rare disease. Then when they get to the drug development phase, a team that’s shared through OpenTreatments can help them navigate that process, which is less disease specific. That’s where some of that scalability comes into play.
And Ramesh’s work on OpenTreatments and rare diseases made him think about the healthcare and pharmaceutical industries in a much bigger way. He is upset and frustrated by a system that ignores sick and suffering people if there’s not enough money to be made treating them.
That’s one of the reasons that Bill Gates became involved with vaccines through the Bill & Melinda Gates Foundation. There were so many diseases hammering lower-income countries, but pharmaceutical companies didn’t have an incentive to treat them.
There wasn’t enough money to be made. Ramesh sees parallels in the world of rare diseases. He wants to untangle the knotted up web of drug development so that it can work more effectively. So that it won’t leave the Raghavs behind.
Ramesh: It’s a web of things. And over time, it has evolved to add more layers of complexity into the web. And now it’s like a hairball. Previously, it was a beautiful web and a simple web that had a purpose. Now you have to just keep looking back for a time when the web was simple and ask, “Why was this web created this way? And what added complexities into the web?” You have to untangle this mess of hairball and make it a beautiful web. How do you do that?
There are many ways of doing it, and typically it’s by governing the flow of money. If you govern the flow of money in the right direction, and if you push enough money into it, the web will sort of reconfigure into a new state. That’s the sort of a theoretical way of thinking. The more practical way to say it is, we do not have a lot of therapies today in the market. That’s because the regulators haven’t approved a lot of therapies. The regulators haven’t approved them because the biotech is not producing a lot of therapies. Biotech is not producing a lot because academia is not producing a lot of preclinical data. Academia is not producing because they’re not incentivized to do it. And they’re not incentivized, because [the National Institutes of Health] is not incentivizing it, going back to the regulators.
We solve this is by putting a lot more people into building therapies. Imagine rather than having 10 patient foundations, or 100 patient foundations today driving research, if there were millions of people driving research, how big the output would be. At that scale of preclinical research and research output, how many therapies will be entering the market? Do we have enough VC funds to even fund this many companies? Do we have manufacturing capacities to actually satisfy this? Do we have regulatory frameworks?
If you kind of walk it back, the starting point is actually getting more people to build more therapies, and everything else will fall in place. And that is what I’m trying to do by decentralizing drug development.
LS: And the lever that Ramesh has to pull is OpenTreatments.
Ramesh: With OpenTreatments, I’m able to support established foundations that have a scientific board. They have made some progress already, have raised some funds, they know what they’re doing. I’m not able to help people that have just gotten the diagnosis that don’t really know what they’re doing at this point.
It takes a lot of emotional transformations for you to be able to work on something like this for your own personal good. The transformation is primarily the acceptance of risk, is the acceptance that we will fail, will fail miserably, it might not be in time for our kids. It takes a lot of grit and determination to be able to do this. Some parents have that acceptance, and they get the acceptance right away. Some parents don’t.
I try to talk to as many people as I can. And for folks that have decided to start a foundation, I have collaborated with the Orphan Disease Center at the University of Pennsylvania. They are providing exceptional support for families to get started on this journey. Many of them are working with the ODC, they’re jump-starting to get the foundation solid.
In other cases, my story has provided hope to a lot of people. It’s shown that there is something else that you can do besides struggling. So I continue to share my story precisely because of that, so other people can be more hopeful and feel less emotional, and be driven to action.
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