Tech-savvy dad launches open-source platform to save children with rare diseases – including his son

Sanath Kumar Ramesh with his son Raghav. (Courtesy photo of the Ramesh family)

On a fine August day in a Bellevue park, Sanath Kumar Ramesh received a call from his son’s doctor as he was preparing to cut the cake for his little boy’s first birthday.

He finally knew what was making his child sick, what prevented Raghav from eating alone, lifting his head, or holding a toy. It was a mutation in a single point in his genetic code.

“When I heard this news that they had found out the name of the disease, we were very excited,” said Ramesh. “The next question I asked her was, ‘OK, great. Can you make an appointment in the next week? I’ll come and get some medicine. ‘”

But there was more.

“Wait,” said the doctor.

She told Ramesh that almost all babies with the disease die a few weeks after they are born. There was no treatment. What the doctor didn’t say was that if Raghav was to survive, happiness and his family would have to save him.

As his son nears his third birthday, Ramesh is working with researchers on gene therapy to correct Raghav’s rare condition, and he is leading a unique effort to help others do the same.

Image from the OpenTreatments platform. (Click to enlarge.)

Ramesh, a software engineering manager at Amazon, is the founder and CEO of the OpenTreatments Foundation, which this week launched an open source platform called OpenTreatments. The platform is a playbook and collection of resources for people facing the daunting challenge of finding treatments and cures for loved ones with rare diseases.

There are more than 263 million people worldwide with unusual diseases, many of which are chronic or fatal and most of them affect children. Researchers estimate that there are more than 6,000 different rare diseases. Because it can cost billions of dollars to develop a new gene therapy for a biotech company, the vast majority of these conditions are untreated.

“It’s really up to patients and families to control this if they want to do something,” said Ashley Winslow, chief scientist of Odylia Therapeutics. The nonprofit works on eye diseases and supports patient groups desperate for therapy. “Instead of letting people fidget and find out for themselves, they [OpenTreatments] The platform tries to get them on a path. “

Four more cases

The condition that affects Raghav is known as Sedaghatian-type spondylometaphyseal dysplasia (SSMD). It causes irregular heartbeat, as well as abnormalities in the skeleton and central nervous system. SSMD is the result of a genetic mutation in which free oxygen radicals and iron run amok into cells and kill them.

Dr. Russ Saneto of Seattle Children’s Hospital knows four other cases: two children in San Diego, one in Japan and another child in Belgium who have died.

“That’s it,” said Saneto. “We’re talking about a really rare disorder.”

Seattle Children’s doctors were able to diagnose Raghav through exome sequencing, which examines the stretches of DNA that are converted into proteins.

After discovering the mutation, Saneto joined a small constellation of researchers scattered across the country working under similar conditions to seek their help. Part of his challenge was to confirm that the mutations Raghav was carrying were causing his health problems.

Saneto and colleagues grew cells containing Raghav’s genetic material and other cells with genes from his father to study their differences. It is difficult to keep Raghav’s cells alive, said Saneto. Ultimately, they succeeded, and when the scientists inserted unmutated copies of the gene into Raghav’s cells, they behaved normally. It was the evidence they needed as to the cause of his disease and opened the door to gene therapy research.

But Raghav needed help immediately. After hearing his son’s diagnosis, Ramesh began Googling and reading the relevant scientific literature. He limited the existing pharmaceutical options to 36 drugs. His son’s health care providers picked four of them, and within less than a month of his first birthday, Raghav was in a cocktail that contained large doses of vitamin E and other antioxidants.

The children’s doctors in Seattle applied for and received special FDA approval to treat Raghav with a drug originally developed for another iron-related disease. Treatment appears to have stopped the disease’s progression but is not a cure.

“He holds his own,” said Saneto. “And we’re trying to figure out how we can make it better.”

“Something for my son”

Between working at Amazon, working at the OpenTreatments Foundation, and having his wife caring for his son, Ramesh only got four or five hours of sleep at night.

“I stopped about a month ago,” he said after another rare disease parent advised him that Ramesh should keep his own health while he worked to improve his son’s.

Four rare diseases are currently piloted on the OpenTreatments platform, including the one affecting Raghav. Ramesh and a team of volunteers built the platform in collaboration with RareCamp. One day, Ramesh hopes to have a small, paid core of engineers on site while encouraging the volunteers to contribute to the open source effort. The Linux Foundation hosts OpenTreatments.

Ramesh said it could be two or three years before he and his team can develop gene therapy if they’re successful. They raised $ 5 million from friends and family to fund the effort. So much is at stake to help Raghav.

“One of the reasons I started OpenTreatments in the first place was because I was worried I might get it wrong,” said Ramesh. “And I’ve talked to other families and patient foundations, they were also worried they were getting it wrong.”

Hopefully families will improve their chances by sharing their lessons and resources on the public website – which is long but not impossible. Gene therapy has been successful in treating neuromuscular diseases, congenital blindness, and cancer, and innovations are underway. “Next-generation technologies are dramatically expanding the effects of these drugs in treating human diseases,” researchers wrote in a study 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,” said Ramesh. “There are several patient families who have taken this trip and received treatment for their children and for other children.” However, many were unable to save their own children. Ramesh doesn’t want that result.

“I want something for my son today,” he said, “and for other children in the future.”

Leave a Comment