On a beautiful August day in a Bellevue park, just as he was getting ready to cut the cake for his little boys first birthday, Sanath Kumar Ramesh got a call from his sons doctor.
At last he knew what was making his child sick, what was preventing Raghav from being able to eat on his own, raise his head or hold a toy. It was a mutation at a single spot in his genetic code.
When I heard this news, that they found out the name of the disease, we were super excited, Ramesh said. The next question that I asked her was, OK great. Can you set up an appointment the next week? Ill come and get medications.’
But there was more.
Hold on, the doctor said.
She told Ramesh that nearly all babies with this condition pass away a few weeks after birth. There was no treatment. What the doctor didnt say was that if Raghav was to survive, luck and his family were going to have to save him.
As his son is now approaching his third birthday, Ramesh is working with researchers in pursuit of a gene therapy to correct Raghavs rare condition, and he is spearheading a first-of-its-kind effort to help others do the same.
Ramesh, a software engineering manager at Amazon, is founder and CEO of OpenTreatments Foundation, which this week launched an open-source platform called OpenTreatments. The platform is a playbook and collection of resources for people confronting the tremendous challenge of seeking treatments and cures for loved ones with rare diseases.
There are more than 263 million people worldwide with unusual conditions, many of which are chronic or fatal, and most affect children. Researchers estimate there are more than 6,000 different rare diseases. But because it can cost a biotech company billions of dollars to develop a new gene therapy, the overwhelming majority of these conditions lack treatments.
Its really up to patients and families to navigate this if they want anything done, said Ashley Winslow, chief scientific officer for Odylia Therapeutics. The nonprofit works on ocular diseases and assists patient groups desperate for therapies. Instead of letting people flounder and figure it out on their own, the [OpenTreatments] platform is trying to set them on a path.
Four other cases
The condition that affects Raghav is called Sedaghatian type Spondylometaphyseal Dysplasia (SSMD). It 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.
Dr. Russ Saneto of Seattle Childrens Hospital knows of four other cases: two kids in San Diego, one in Japan and another child in Belgium who died.
Thats it, Saneto said. Were talking about a really rare disorder.
Doctors at Seattle Childrens were able to diagnose Raghav by doing exome sequencing, which scrutinizes the stretches of DNA that are turned into proteins.
After pinpointing the mutation, Saneto linked together a small constellation of researchers scattered around the country who work on related conditions to enlist their help. Part of his challenge was to confirm that the mutations that Raghav carried were causing his health abnormalities.
Saneto and colleagues grew cells containing Raghavs genetic material and other cells with genes from his dad to explore their differences. It was hard to keep Raghavs cells alive, Saneto said. They ultimately succeeded, and when the scientists added non-mutated gene copies into Raghavs cells, they behaved normally. It was the proof that they needed for the cause of his illness, opening the door to research on gene therapies.
But Raghav needed help right away. After Ramesh learned his sons diagnosis, he began Googling and reading the relevant scientific literature. He narrowed down the existing pharmaceutical options to 36 drugs. His sons healthcare providers selected four of them, and within less than a month after his first birthday, Raghav was taking a cocktail that included big doses of vitamin E and other antioxidants.
The Seattle Childrens doctors also applied for and received special FDA approval to treat Raghav with a drug originally developed for a different iron-related disease. The treatment appears to have stopped the diseases progression, but is not a cure.
Hes holding his own, Saneto said. And were trying to figure out how to make him way better.
Something for my son
Between his job at Amazon, working on OpenTreatments Foundation, and, alongside his wife, providing care for his son, Ramesh was down to four or five hours of sleep at night.
I stopped doing that about a month ago, he said, after another rare disease parent advised him that Ramesh needed to preserve his own health while he labored to improve his sons.
There are four rare diseases running currently running as pilot projects on the OpenTreatments platform, including the one afflicting Raghav. Ramesh and a team of volunteers built the platform through a collaboration named RareCamp. One day Ramesh hopes to have a small, paid core of engineers working on the site while still encouraging volunteers to contribute to the open-source effort. The Linux Foundation is hosting OpenTreatments.
Ramesh said it could take two or three years before he and his team is able to develop a gene therapy, if theyre successful. They have raised $5 million from friends and family to fund the effort. Theres so much at stake in the race to help Raghav.
One of the reasons I started OpenTreatments in the first place was because I was worried that I might do it wrong, Ramesh said. And I was talking to other families and patient foundations, they worried, too, that they were doing it wrong.
Hopefully by sharing their lessons and resources on the public site, the families will improve their odds which while long, are not impossible. Gene therapy has been successful in treating neuromuscular disease, inherited blindness and cancer, and innovations are underway. Next-generation technologies are dramatically expanding the impact of these medicines on treating human disease, wrote researchers in a study from last year. Another report predicted that more than 1 million patients will have received gene therapy by 2035.
There is light at the end of the tunnel, Ramesh said. There are several patient families that have done this journey, that have gotten a treatment for their kids and for other kids. Many, however, werent able to save their own children. Ramesh doesnt want that outcome.
I want something for my son today, he said, and for other kids in the future.