Engineer is using his sons rare disease – Sanath Kumar Ramesh and his wife Ramya experienced typical first-time-parent jitters before the birth of their son. Ramesh, an Amazon software engineering manager, was overjoyed to welcome his first child. He was prepared for the responsibilities and rewards of parenthood.
Raghav was born in August 2018, and Ramesh’s life began to change in unexpected ways.
On this episode of the Tech News Health Tech Podcast, we catch up with Ramesh to learn more about his compelling and inspiring story. We previously covered Ramesh and Raghav’s doctors’ efforts to treat Raghav.
In this podcast, we delve deeper into Ramesh’s experience as a father and a talented tech engineer working to help both his son and others who are fighting to save loved ones suffering from rare diseases. [Engineer is using his sons rare disease]
Ramesh: Everything was fine during pregnancy, and everything was fine until Raghav was born. He was so tiny and precious when he was born. I recall holding him in my hands and reflecting on how my life had changed. My life has changed not because of a bad event, but because I now have a purpose. And the goal is this baby. And we were overjoyed for the first three or four hours after Raghav was born, until a doctor approached us and said, “There is something wrong with Raghav.”
She was perplexed by what was going on at the time. “There’s something wrong with Raghav,” she said. He does not appear to be a typical child. We believe Raghav has a neurological problem and that something is fundamentally wrong with him to the point where he could have a lifelong illness. I had no idea what a neurological issue was. We assumed it was something you could treat with a pill and be done with it.
We were in the hospital for the next 21 days trying to figure out what was wrong with him. Nonetheless, we returned home without a response. And when we got home, we hoped it was just the birth trauma, that it was a one-time occurrence, and that it would go away with time. [How this tech engineer is using his sons rare disease]
Lisa Stiffler of Technews writes: As Ramesh would discover, Raghav faced greater difficulties than he could have imagined. Instead of despair, Ramesh used his problem-solving, engineering nature to solve the problem, paving the way for his family and many others in similar situations.
Raghav appears in early photographs as a bright-eyed, smiling baby with long eyelashes and black hair. He’s so cute. During his first year, Sanath and Ramya worked tirelessly to help their son grow and develop normally. He couldn’t, however, do the things that a normal baby could. To eat, he required a feeding tube. He bit his tongue and lips when he got his first teeth, an exciting developmental milestone. Raghav lacked the necessary motor skills to control his movements.
Ramesh had no idea what was wrong with Raghav for months. When his son’s first birthday rolled around, the family was ready to put their differences aside and celebrate in a park in Bellevue, just east of Seattle. It was a beautiful, sunny summer afternoon in the Pacific Northwest.
Ramesh: Just as I was about to cut the cake, I got a call from Raghav’s doctor, who said, “Oh, by the way, we found out what’s wrong with Raghav. We figured out what was wrong with him. He has this genetic condition as a result of a mutation in the GPX4 gene.” [How this tech engineer is using his sons rare disease]
And I was overjoyed in that moment. “Oh, this is awesome,” I told her. OK, we’ll come back next week to get his medications.” “Hold on, there is no medication for this disease,” she said. In fact, we believe Raghav is the only child alive who has this condition. Because all of the children with this disease died within a few weeks of birth.”
You know, here I am, getting ready to cut the cake, and someone tells me that my son is fortunate to be alive today. And it was at that point that everything in my life changed. When my son was born, I thought my life had been transformed. On his first birthday, it was transformed once more.
LS: It’s agonising to think about hearing this news. Consider how you would deal with this new reality. Researchers estimate that there are over 6,000 different rare diseases, including Raghav’s. An estimated 263 million people worldwide suffer from unusual conditions, many of which are chronic or fatal, with children bearing the brunt of the burden. Because of their rarity, almost no treatments are available.
This was a wake-up call for Ramesh. [How this tech engineer is using his sons rare disease]
Ramesh: I’m a trained software engineer. And one thing that has been drilled into my head is that I must solve problems. And at the time, I was getting really, really excited by really difficult problems. And I thought debugging software was the most difficult problem to solve.
When I was presented with this problem, which is that my son has a genetic disease, I saw it as one that I needed to solve. I began Googling about this disease, which I couldn’t even spell at the time. I began researching this gene on the internet. And I needed to understand what a gene was in the first place. I knew there were things called genes, but I have no idea why they are in my body. And it took some digging for me to realise that there is virtually nothing about this disease in the literature.
LS: Raghav has a condition that is extremely rare and has a long name: Sedaghatian type Spondylometaphyseal Dysplasia. It’s so uncommon that it didn’t have an acronym until Ramesh came up with one: SSMD.
Cardiovascular arrhythmias, as well as skeletal and central nervous system abnormalities, are caused by the condition. SSMD is caused by a genetic mutation that causes oxygen free radicals and iron to run amok inside cells, killing them. [How this tech engineer is using his sons rare disease]
Dr. Russ Saneto, one of Raghav’s doctors at Seattle Children’s Hospital, said he is aware of four other cases around the world involving children who died: two in San Diego, one in Japan, and another in Belgium.
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.
Then I realised that, given the severity of this disease, finding a new treatment would be impossible. Because I discovered during my search that developing new therapies takes 8 to 10 years and costs billions of dollars that a biotech company would invest in. And I don’t have the time or the money to do it.
LS: But Ramesh was astute and resourceful. And his son required assistance right away. Given that a breakthrough treatment was not imminent, he considered what was, which was the local pharmacy. [How this tech engineer is using his sons rare disease]
Ramesh wondered if any existing medications could help Raghav. Right now, something off the shelf. They came up with 36 drugs that could be repurposed for Raghav’s condition while working with his son’s doctors at Seattle Children’s Hospital, and settled on a cocktail of four.
Ramesh devised a treatment that includes vitamin E and other antioxidants within a month of learning his son’s diagnosis.
And the doctors were able to successfully petition the FDA to use another drug being developed by a pharmaceutical company for a different disease. Raghav’s health appears to have improved as a result of the approach. However, it is not a long-term solution.
Ramesh: Long-term treatment for these conditions involves the use of a technology known as gene replacement therapy. The concept is straightforward. My son was born with a GPX4 gene mutation. In software terms, a mutation is a bug. There are several characters that encode this gene, and one of them is misspelt. [How this tech engineer is using his sons rare disease]
The idea behind gene replacement therapy is to replace a faulty gene with a healthy one. Doesn’t that sound simple? But, unfortunately, it is not that simple. There are numerous procedures that must be followed. It’s quite complicated. And constructing a treatment for my son will cost between $5 and $7 million. And it still costs a lot more money to conduct a clinical trial in order to obtain FDA approval and make the drug available to a larger population worldwide.
My son’s condition currently has only nine patients worldwide, making it extremely rare. At this scale, we are unlikely to receive commercial approval from the FDA, which is fine; we will simply continue to treat patients in an experimental setting as much as possible.
LS: Ramesh is not alone in his search for a treatment for a rare disease in a family member. There are numerous foundations established on behalf of loved ones suffering from rare diseases. The organisations raise whatever funds they can and attempt to recruit experts to assist them in developing gene therapy treatments. It’s expensive, and the risks are high in some ways — you’re literally trying to improve or save the life of someone you care about. The stakes were high for Ramesh.
Ramesh: When I first started working on my son’s gene therapy, I thought, well, I can do a lot of work, I can work 24 hours a day, 365 days a year. But what if I don’t succeed? What if the people I’m with fail? So I began asking other patients and patient foundations about their experiences developing gene therapies, hoping to learn about their successes as well as their failures. [How this tech engineer is using his sons rare disease]
What I discovered is that many patient foundations fail, struggle, and make mistakes. They must reset several times. They have raised millions of dollars in order to obtain treatment. When that happens, perhaps 10 or 20 years after they started, their children are unlikely to benefit from it. They are either too old or too sick to participate in trials. That is not a happy ending for me. As a result, I felt compelled to take precautions against the possibility of my own failure.
LS: This prompted Ramesh to employ a highly technical concept: open-source engineering. Ramesh decided to bring along others who are on parallel journeys while assembling a team and searching for a cure for his son.
He is now the founder and CEO of the OpenTreatments Foundation, a non-profit that has recently launched the OpenTreatments open-source platform. The platform is a playbook and collection of resources for foundations and individuals seeking rare disease treatments.
Four rare diseases, including Raghav’s, are currently being treated as pilot projects on OpenTreatments. Ramesh and a team of volunteers created the platform as part of a RareCamp collaboration. [How this tech engineer is using his sons rare disease]
Ramesh: I ended up identifying a mechanism through which I can assist not only my son’s gene therapy, but also many other families. And, as a software developer obsessed with scale, which is what we do at work, I wanted to be able to help hundreds of thousands of families rather than just one or two. I believe that eventually, millions of patients will be able to drive research. That is the guiding principle of OpenTreatments. That’s how I came up with the idea of creating a software platform.
OpenTreatments gives patient foundations a clear roadmap for developing treatments. We connect them with the people they need to advance their programmes. And we connect them with the scientific infrastructure they need to advance their research. And, hopefully, we will be able to attract funding to assist the patient foundations in moving forward. This is how OpenTreatments came to be as a result of me hedging my own risk.
LS: Work is being done to assist Raghav. Ramesh has put together a team of experts from universities all over the world. They are researching the GPX4 gene as well as the biology of SSMD. They’re working towards the ultimate goal of developing a gene therapy, but it could take three years or more.
Meanwhile, Ramesh’s wife continues to work to raise funds for the effort. They’ve raised about $5 million so far. They’re also collaborating with Raghav’s doctors to obtain FDA approval to use a second experimental drug. [How this tech engineer is using his sons rare disease]
The idea behind OpenTreatments is that each foundation raises its own funds and conducts genetic and disease research for each unique, rare disease. When they reach the drug development stage, an OpenTreatments-shared team can assist them in navigating that less disease-specific process. This is where some of the scalability comes in.
And Ramesh’s work on OpenTreatments and rare diseases prompted him to consider the healthcare and pharmaceutical industries in a broader context. He is irritated and frustrated by a system that disregards sick and suffering people if there isn’t enough money to be made treating them.
That is one of the reasons why Bill Gates, through the Bill & Melinda Gates Foundation, became involved with vaccines. There were so many diseases wreaking havoc on low-income countries, but pharmaceutical companies had no incentive to treat them.
There wasn’t enough money to go around. In the world of rare diseases, Ramesh sees parallels. He wishes to untangle the tangled web of drug development in order for it to function more effectively. So that the Raghavs are not left behind. [How this tech engineer is using his sons rare disease]
Ramesh: It’s all interconnected. And it has evolved over time to add more layers of complexity to the web. And it’s now the size of a hairball. It used to be a beautiful web and a simple web with 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 complexities have been introduced into the web?” You must untangle this tangled mess of hairballs and turn it into a lovely web. How do you go about doing that?
There are numerous approaches, the most common of which is to control the flow of money. If you control the flow of money in the right direction and put enough money into it, the web will reconfigure itself into a new state. That is an example of theoretical thinking. To put it another way, there aren’t many therapies on the market right now. This is because regulators have not approved many therapies.
Because biotech does not produce a large number of therapies, regulators have not approved them. Biotechnology is not producing much because academia is not producing much preclinical data. Academia is not producing because it is not financially motivated to do so. And they’re not incentivized because [the National Institutes of Health] isn’t incentivizing it, so it’s up to the regulators to do so.
We can solve this by enrolling a larger number of people in building therapies. Consider how large the output would be if, instead of having 10 or 100 patient foundations driving research today, there were millions of people driving research. How many therapies will enter the market at that scale of preclinical research and research output? Do we have enough venture capital funds to fund this many companies? Do we have the manufacturing capacity to meet this demand? Do we have regulatory frameworks in place? [How this tech engineer is using his sons rare disease]
If you take a step back, the starting point is actually more people building more therapies, and everything else will fall into place. That is what I am attempting to accomplish by decentralising drug development.
LS: The lever Ramesh must pull is OpenTreatments.
Ramesh: I’m able to support established foundations with a scientific board through OpenTreatments. They’ve already made some progress, raised some funds, and know what they’re doing. I can’t help people who have just been diagnosed and don’t know what they’re doing at this point.
It takes a significant amount of emotional transformation for you to be able to work on something like this for your own personal benefit. The transformation is primarily the acceptance of risk, the acceptance that we will fail, and that we will fail miserably, and that we may not succeed in time for our children. To be able to do this, you must have a lot of grit and determination. Some parents have that acceptance and receive it right away. Some parents, however, do not. [How this tech engineer is using his sons rare disease]
I try to speak with as many people as possible. And, for those who have decided to establish a foundation, I have worked with the University of Pennsylvania’s Orphan Disease Center. They are providing exceptional assistance to families as they embark on this journey. Many of them are collaborating with the ODC, and they’re laying the groundwork.
In other cases, my story has given many people hope. It has been demonstrated that there are alternatives to struggling. As a result, I will continue to share my story in order for others to be more hopeful, less emotional, and motivated to act.
