By Adam Alberti
Most everyone is familiar with the fundraising that comes from disease awareness days. The pink ribbons for breast cancer, the red ribbon for AIDS. Less familiar – and there’s perhaps some irony in that – is the Feb. 28 date recognized internationally to call attention to rare diseases. “Rare” may mean scarce or unusual, but measured cumulatively, the number is not at all small: Global Genes, a leading rare disease patient advocacy group, lists more than 7,000 different types of rare diseases and disorders in the world, 80 percent of them genetic.
Especially tragic, nearly half of all those who suffer from a rare disease are children. Thirty five percent of kids afflicted with a rare disease die in the first year of life, according to national statistics, and another 30 percent do not live to see their fifth birthday.
These are difficult facts to confront as a new parent reeling from unexplained disease at birth. But for one Peninsula mother, these statistics became a motivator and a life’s mission.
Kim Lodato Nye, who grew up in Redwood City and Portola Valley, is executive director and board chair of TESS Research Foundation, a local nonprofit founded to find treatments and a cure for SLC13A5 Deficiency, a rare disease that brings on life-threatening seizures within the first days after birth. “It’s kind of a mouthful as far as disease names go,” Kim said, “but SLC13A5 is the genetic marker for the condition.”
The cause is not fully understood but has been isolated to the transfer into the cells of citrate, a small molecule that is digested in food. In people with SLC13A5 Deficiency, changes to the amino acids seem to alter the amounts of citrate that reaches the cell. That alteration is what triggers the seizures and other less severe symptoms of the disease. But this newfound knowledge has been a long time coming – and came as a result of the Nye family’s experience.
Almost 14 years ago, Kim and her husband Zach, a Menlo Park native, had their first child. Tessa Madeline Nye was born in London, where Zach was studying economics at London Business School and Kim was getting her master’s degree in Classics at Oxford University. It was an optimistic time in the couple’s life filled with opportunity and dreams of a large and healthy family.
Tessa was a challenging birth, but that was nothing compared to what followed. The baby’s first seizure happened within hours of birth. Other seizures followed, and as the new parents brought Tessa home, they began to grapple with what they did not yet realize was a rare genetic disease.
“When we say seizures, we are talking hundreds of them a day, some more serious than others, but all of them impactful,” Kim said. “We lost count on how many times an ambulance has showed up at our house after a grand mal seizure.”
Over the next decade, the family was frustrated in pursuit of an answer as to why this was happening and how to help. “It’s heartbreaking to see your child’s health fail so dramatically and to have nobody be able to tell you why,” Kim said. The Nyes tried different drugs to control Tessa’s seizures, but their interactions were a source of frustration – and a constant reminder – that drugs might mask symptoms but not address the underlying disorder.
They were challenged by the lack of answers. “In the early years we had more optimism. We were determined that if we could just find the cause, we could stop the seizures and provide relief,” Kim recalled. “As the years progressed our optimism turned more to determination of just finding relief from the hospital trips and the devastating impacts it all had on Tessa.”
Despite the effort, a diagnosis remained elusive. The Nyes consulted with the best experts, not just the best at Stanford and UCSF, but the best from all over the world. “My wife is a force. She always found the latest expert in the field and we were traveling all over the country to see the most prominent people,” Zach said. “But in the end, I always felt that Kim gave them more of an education than anything else. We were told that Tessa was simply a genetic anomaly of some variety. The best explanation of dozens of experts was that Tessa was a statistical fluke and the odds of it happening again were like getting struck with lightning twice.”
Fast forward a decade later. The Nyes’ dreams of a large, healthy family were being realized with the additions of daughters Lily and Maggie, now 10 and eight respectively. Then the “lightning” that never strikes twice did. Colton, a fourth child, was born in 2013. Within hours of birth, he too suffered seizures. “It was devastating,” Kim said. “Truly heartbreaking to see it happen again. Having seen Tessa experience true suffering at the hands of this disease, we knew what was in store for Colton.”
Once again, the Nyes dealt with the pain and grief of seeing one of their children impacted by the seizure disorder. But the tragedy brought with it a new set of opportunities, new roads to travel in pursuit of an understanding of a disease that was clearly not just some sort of random genetic anomaly, but instead a specific one. Having two kids in the same family with the same disorder made hunting the genome for a match doable. In relatively short order after Colton’s birth, the cause of the seizures was known: SLC13A5 Deficiency was now an official rare disease.
“While we were thrilled to finally know what caused the seizures, we also realized that this didn’t drastically change anything,” Kim said. Only about half of all rare diseases have specific foundation support or research into a treatment and a cure. But finally having a confirmed cause for their children’s disorder gave the beleaguered couple something that was also rare. “It did provide us a resurgence of hope that we were in short supply of,” Kim said.
The Menlo Park couple leveraged that hope into action and formed TESS Research Foundation in 2015. “In the end, we are just better at doing something than doing nothing,” Kim said. “I care deeply about the children, like mine, who have been diagnosed with this disease and the newborns who will be diagnosed. It is maddening to think that a cure is out there, and no one is even looking for it. Science is making rapid progress with single-gene diseases, and we live in a community that can move mountains. Why not see if our community can move this molehill?” Kim asked.
In years since the SLC13A5 Deficiency was recognized, many children have been diagnosed, and the foundation was created to advance a cure for the growing number of those affected. The thought that it could be as simple as an added protein or a pill inspires the Nyes and their supporters, and the foundation has made remarkable progress since its formation. More than $400,000 has been raised in just two short years – an impressive feat for a rare disease foundation – and the board is striving to be “entrepreneurial” in awarding funding to promising research that can catapult understanding and advance a cure. Through a blue-ribbon scientific board comprised of doctors from Stanford, Baylor, UCSF, UCSD, and Rady Children’s Hospital, the TESS Research Foundation has funded research that has successfully advanced zebrafish, fly, mouse and cellular models of the disease, critical first steps to testing drugs. Researchers have made remarkable progress in understanding how the disease works and facilitating its diagnosis.
Lee Scheuer, a local businessman known for raising funds for more traditional causes, has gone all in on the effort. “I am so proud to be a member of the TESS Research Foundation Board, which has accomplished so much under Kim Nye’s direction,” Scheuer said. “Kim’s knowledge of the disease and relentless desire to find a cure has motivated the board members to achieve the goal we set out to do two years ago. I am confident with additional resources and the dedication of the amazing TESS research team we will dramatically improve the lives of these children.”
Therein lies the challenges for TESS Research Foundation and the many others like it which focus on rare disease research. Resources are hard to come by. Nearly all the funding that goes into researching disease and cures from the federal government and academia goes into the big “known” diseases. On an international level, it wasn’t until 2008 that Rare Disease Day was even established by the European Organization for Rare Diseases.
Precisely for that reason, contributions to support rare disease research can make an outsized impact for kids and their families. “We are so close, but at the same time there is so much to do,” Kim said. “Every day that goes by without a cure or treatment results in thousands of seizures for the kids who are suffering.”
Photo courtesy of TESS Research Foundation
Climate magazine publisher Adam Alberti is a member of the board of the TESS Research Foundation, and more detail about its mission and activities can be found at www.tessresearch.org. More information on rare diseases can also be found at the National Organization for Rare Disorders at www.rarediseases.org.