When doctors couldn’t stop her daughter’s seizures, this mom earned a PhD and found a treatment herself.
Savannah Salazar (left) and her mother, Tracy Dixon-Salazaar, who earned a PhD in neurobiology in the quest for a treatment of her daughter's seizure disorder.
Twenty-eight years ago, Tracy Dixon-Salazaar woke to the sound of her daughter, two-year-old Savannah, in the midst of a medical emergency.
“I entered [Savannah’s room] to see her tiny little body jerking about violently in her bed,” Tracy said in an interview. “I thought she was choking.” When she and her husband frantically called 911, the paramedic told them it was likely that Savannah had had a seizure—a term neither Tracy nor her husband had ever heard before.
Over the next several years, Savannah’s seizures continued and worsened. By age five Savannah was having seizures dozens of times each day, and her parents noticed significant developmental delays. Savannah was unable to use the restroom and functioned more like a toddler than a five-year-old.
Doctors were mystified: Tracy and her husband had no family history of seizures, and there was no event—such as an injury or infection—that could have caused them. Doctors were also confused as to why Savannah’s seizures were happening so frequently despite trying different seizure medications.
Doctors eventually diagnosed Savannah with Lennox-Gaustaut Syndrome, or LGS, an epilepsy disorder with no cure and a poor prognosis. People with LGS are often resistant to several kinds of anti-seizure medications, and often suffer from developmental delays and behavioral problems. People with LGS also have a higher chance of injury as well as a higher chance of sudden unexpected death (SUDEP) due to the frequent seizures. In about 70 percent of cases, LGS has an identifiable cause such as a brain injury or genetic syndrome. In about 30 percent of cases, however, the cause is unknown.
Watching her daughter struggle through repeated seizures was devastating to Tracy and the rest of the family.
“This disease, it comes into your life. It’s uninvited. It’s unannounced and it takes over every aspect of your daily life,” said Tracy in an interview with Today.com. “Plus it’s attacking the thing that is most precious to you—your kid.”
Desperate to find some answers, Tracy began combing the medical literature for information about epilepsy and LGS. She enrolled in college courses to better understand the papers she was reading.
“Ironically, I thought I needed to go to college to take English classes to understand these papers—but soon learned it wasn’t English classes I needed, It was science,” Tracy said. When she took her first college science course, Tracy says, she “fell in love with the subject.”
Tracy was now a caregiver to Savannah, who continued to have hundreds of seizures a month, as well as a full-time student, studying late into the night and while her kids were at school, using classwork as “an outlet for the pain.”
“I couldn’t help my daughter,” Tracy said. “Studying was something I could do.”
Twelve years later, Tracy had earned a PhD in neurobiology.
After her post-doctoral training, Tracy started working at a lab that explored the genetics of epilepsy. Savannah’s doctors hadn’t found a genetic cause for her seizures, so Tracy decided to sequence her genome again to check for other abnormalities—and what she found was life-changing.
Tracy discovered that Savannah had a calcium channel mutation, meaning that too much calcium was passing through Savannah’s neural pathways, leading to seizures. The information made sense to Tracy: Anti-seizure medications often leech calcium from a person’s bones. When doctors had prescribed Savannah calcium supplements in the past to counteract these effects, her seizures had gotten worse every time she took the medication. Tracy took her discovery to Savannah’s doctor, who agreed to prescribe her a calcium blocker.
The change in Savannah was almost immediate.
Within two weeks, Savannah’s seizures had decreased by 95 percent. Once on a daily seven-drug regimen, she was soon weaned to just four, and then three. Amazingly, Tracy started to notice changes in Savannah’s personality and development, too.
“She just exploded in her personality and her talking and her walking and her potty training and oh my gosh she is just so sassy,” Tracy said in an interview.
Since starting the calcium blocker eleven years ago, Savannah has continued to make enormous strides. Though still unable to read or write, Savannah enjoys puzzles and social media. She’s “obsessed” with boys, says Tracy. And while Tracy suspects she’ll never be able to live independently, she and her daughter can now share more “normal” moments—something she never anticipated at the start of Savannah’s journey with LGS. While preparing for an event, Savannah helped Tracy get ready.
“We picked out a dress and it was the first time in our lives that we did something normal as a mother and a daughter,” she said. “It was pretty cool.”
Slowing Aging Could Transform Society As We Know It
A young woman portrayed next to her old counterpart.
People's lives have been getting longer for more than a century. In 1900, in even the wealthiest countries, life expectancy was under 50, according to the World Health Organization. By 2015, the worldwide average was 74, and a girl born in Japan that year could expect to live to 87. Most of that extra lifespan came from improvements in nutrition and sanitation, and the development of vaccines and antibiotics.
People's lives have been getting longer for more than a century. In 1900, in even the wealthiest countries, life expectancy was under 50, according to the World Health Organization. By 2015, the worldwide average was 74, and a girl born in Japan that year could expect to live to 87. Most of that extra lifespan came from improvements in nutrition and sanitation, and the development of vaccines and antibiotics.
The question is, how will slowing aging change society?
But now scientists are trying to move beyond just eliminating the diseases that kill us to actually slowing the aging process itself. By developing new drugs to tackle the underlying mechanisms that make our bodies grow old and frail, researchers hope to give people many more years of healthy life. The question is, how will that change society?
There are several biological mechanisms that affect aging. One involves how cells react when they're damaged. Some die, but others enter a state called senescence, in which they halt their normal growth and send out signals that something's gone wrong. That signaling causes inflammation at the sight of a wound, for instance, and triggers the body's repair processes. Once everything is back to normal, the senescent cells die off and the inflammation fades. But as we age, the machinery for clearing senescent cells becomes less efficient and they begin to pile up. Some researchers think that this accumulation of senescent cells is what causes chronic inflammation, which has been implicated in conditions such as heart disease and diabetes.
The first clinical trial in humans of senolytic drugs is happening now.
In 2015, researchers at the Mayo Clinic in Minnesota and the Scripps Research Institute in Florida tested the first so-called senolytic drugs, which cause senescent cells to die. After the scientists treated mice with a combination of an anti-cancer drug and a plant pigment that can act as an antioxidant, some of the senescent cells shrank away and caused the mouse's heart function to revert to that of a much younger mouse.
"That suggests that senescence isn't just a consequence of aging, it's actually a driver of aging," says Paul Robbins, a professor of molecular medicine at Scripps and one of the researchers involved. Other animal studies have found that reducing the number of senescent cells improves a variety of age-related conditions, such as frailty, diabetes, liver disease, pulmonary fibrosis, and osteoporosis.
Now the same researchers are moving those tests to humans in the first clinical trials of senolytic drugs. In July 2016, the Mayo Clinic launched what may be the first clinical trial of senolytic therapy, studying the effect of the two drugs, called dasatinib and quercetin, on people with chronic kidney disease, which they hope to complete in 2021. Meanwhile Mayo and Scripps researchers have identified six different biochemical pathways that give rise to senescence, along with several drug candidates that target those pathways. Robbins says it's likely that different drugs will work better for different cells in the body.
Would radical life extension lead to moral deterioration, risk aversion, and an abandonment of creativity?
In Robbins' work, treating mice with senolytic drugs has extended their median lifespan—the age at which half the animals in his experiment have died—by about 30 percent, but hasn't extended the maximum lifespan. In other words, the oldest mice treated with the drugs died at the same age as mice who hadn't been treated, but more of the mice who received senolytics lived to that ripe old age. The same may turn out to be true for humans, with more people living to the limits of the lifespan—estimated by some to be about 115—but no one living much longer. On the other hand, Robbins says, it's early days for these therapies, and it may turn out that delaying aging actually does push the limit of life farther out.
Others expect more radical extensions of human life; British gerontologist Aubrey DeGray talks about people living for 1000 years, and people who call themselves transhumanists imagine replacing body parts as they wear out, or merging our minds with computers to make us essentially immortal. Brian Green, an ethicist at Santa Clara University in California, finds that concept horrifying. He fears it would make people value their own lives too highly, demoting other moral goods such as self-sacrifice or concern for the environment. "It kind of lends itself to a moral myopia," he says. "Humans work better if they have a goal beyond their own survival." And people who live for centuries might become averse to risk, because with longer lives they have more to lose if they were to accidentally die, and might be resistant to change, draining the world of creativity.
Most researchers are focused on "extending the 'healthspan,' so that the people who live into their 90s are vigorous and disease-free."
He's not too worried, though, that that's where studies such as the Mayo Clinic's are headed, and supports that sort of research. "Hopefully these things will work, and they'll help us live a little bit longer," Green says, "but the idea of radical life extension where we're going to live indefinitely longer, I think that is very unrealistic."
Most of the researchers working on combatting aging don't, in fact, talk of unlimited lifespans. Rather, they talk about extending the "healthspan," so that the people who live into their 90s are vigorous and disease-free up until nearly the end of their lives.
If scientists can lengthen life while reducing the number of years people suffer with dementia or infirmity, that could be beneficial, says Stephen Post, a professor of medicine and director of the Center for Medical Humanities, Compassionate Care, and Bioethics at Stony Brook University in New York. But even increasing the population of vigorous 90-somethings might have negative implications for society. "What would we do with all these people who are living so long?" he asks. "Would we stop having children? Would we never retire?"
Adding 2.2 healthy years to the U.S. life by delaying aging could benefit the economy by $7.1 trillion over 50 years.
If people keep working well past their 60s, that could mean there would be fewer jobs available for younger people, says Maxwell Mehlman, professor of bioethics at Case Western Reserve University's School of Law in Ohio. Mehlman says society may have to rethink age discrimination laws, which bar firing or refusing to hire people over a certain age, to make room for younger workers. On the other hand, those who choose to retire and live another two or three decades could strain pension and entitlement systems.
But a longer healthspan could reduce costs in the healthcare system, which now are driven disproportionately by older people. Jay Olshansky, an epidemiologist at the University of Illinois at Chicago School of Public Health, has estimated that adding 2.2 healthy years to the U.S. life by delaying aging would benefit the economy by $7.1 trillion over 50 years, as spending on illnesses such as cancer and heart disease drop.
For his part, Robbins says that the scientific conferences in the anti-aging field, which tend to focus on the technical research, should hold more sessions on social and economic impacts. If anti-aging therapies start extending healthy lifespans, as he and other researchers hope they will within a decade or so, society will need to adjust.
Ultimately, it's an extension of health, not just of longevity, that will benefit us. Extra decades of senescence do nobody any good. As Green says, "Nobody wants to live in a nursing home for 1000 years."