“Imagine you’re five years old, you’ve just had five margaritas, and your parents send you off to school,” says Alice McConnell, sipping hot tea at her kitchen table in northwest Austin. She isn’t setting up a joke, but explaining what it feels like for someone to have succinic semialdehyde dehydrogenase deficiency, a debilitating genetic disorder that is estimated to affect 1 in 460,000 people worldwide. That would suggest there are more than 17,000 active cases today, yet only 450 patients have ever been diagnosed. Two of those are McConnell’s own children.

“If I only had one [kid with it], I might not have answered the call,” she says. “But I got two. The universe hit me upside the head and said, ‘Hey, pay attention.’ ”

“The call” led to Speragen, a biopharmaceutical company McConnell cofounded in 2015 to develop a treatment for her children and others with SSADHD, an initialism for the disorder that’s easier on the tongue. The company also hopes to create a screening test for newborns, which would mean earlier interventions and better outcomes for those with the disease. It’s determined to reach its goals, though that may take years more.

“It’s not a Lifetime movie, and it’s not Lorenzo’s Oil,” McConnell says, referencing the 1992 Oscar-nominated film about a couple who find an effective therapy for their son’s rare disorder within a couple hours of running time. “It’s a mess.”

McConnell gave birth to her first child, Evelyn—a “glowing pink orb” with Frank Sinatra–blue eyes, a shade lighter than her mother’s—in 2009. She quit her civil engineering job managing highway projects to stay home and “drink it all up,” imagining a future filled with playdates at the park, tumbling at the Little Gym, and all the other usual stuff of early childhood. But in the ensuing months, Evelyn couldn’t hold down milk, and while other babies lifted themselves onto their forearms, she lay limp. When McConnell picked her up, she flopped around like a rag doll.

Pediatricians assured McConnell that Evelyn didn’t have a metabolic disorder. They said any such condition would have been detected by the standard infant screening, when a nurse jabbed Evelyn’s foot to collect blood samples on her second day of life. The doctors told McConnell to quit worrying and enjoy her baby. Yet at two years old, Evelyn remained developmentally delayed, both mentally and physically. She could only walk with a leg brace.

McConnell remembers those years as emotionally painful and lonely. Finally, during one pediatric visit, she refused to leave the office until she was told how many metabolic disorders existed—and how many of those were tested for at birth. The doctor Googled it. Out of 800 then-known disorders, the screening checked for just 22. She wondered whether Evelyn could have one of the hundreds not included.

It was a two-year wait to see a metabolic geneticist who might answer that question, so McConnell pushed her pediatrician to order whatever tests the specialist would. One, a urine screen, showed a huge peak for a fatty acid called gamma-hydroxybutyric acid, or GHB, an unmistakable marker of SSADHD. Eight weeks later, her newborn son, Jack, was also determined to have the disorder. “It was crushing,” she says, but she also felt relieved to have a name for what plagued her children, even if had cost her $100,000 to obtain the diagnosis.

“It was a problem,” she says, “but you can solve problems.”

A Dutch scientist, Cornelis Jakobs, first described SSADHD in 1981, after he noticed excess GHB in the urine of a young boy with physical and mental delays. The disorder arises from defects in the ALDH5A1 gene, which tells the body how to make the enzyme succinic semialdehyde dehydrogenase. Without this enzyme, a body can’t break down the amino acid GABA, a neurotransmitter in the brain and spinal cord that regulates muscle tone. GABA then accumulates to catastrophic levels, as do other chemicals, including GHB (its synthetic version, a date-rape drug popularized in the nineties, is known as Liquid X, Georgia Home Boy, or Goop).

These buildups trigger a range of symptoms in SSADHD patients, including seizures, intellectual impairment, behavioral issues (such as aggression, hyperactivity, and obsessive-compulsive disorder), sleep problems, and difficulty communicating. Patients also suffer from reduced muscle tone, which contributed to Jack not walking by himself until age three. “[My kids] sit like this,” McConnell tells me, slumping to one side. Taking annual bluebonnet portraits can be tricky. “You have to tell them, ‘Raise your hands as far as you can above your head to stretch out your spine. Now put your hands down!’ And then you snap the picture.”

In 2004, researchers at Oregon Health & Science University used mice to show that molecular therapy had the potential to correct the condition. But no treatments have reached the market, so doctors address symptoms, prescribing drugs designed to curb epilepsy and other diseases, which come with their own harmful side effects.

Fortunately, Evelyn, now fourteen, and Jack, twelve, don’t have seizures. McConnell prefers to treat them with therapy—physical, speech, occupational, music, aquatic, and even hippotherapy, which strengthens the core through horseback riding—several times a week. These interventions help them walk better and even jog. The kids participate in track and tennis through Special Olympics, and McConnell takes them on hikes to wear them out, which tempers their ADHD and OCD.

Moving their bodies tends to improve their speech, McConnell says. Though Evelyn is a “chatterbox,” her language remains disordered. Jack’s words are limited—”go,” “yeah,” “no,” “Mama,” and “Dada”—so he mostly signs. In special-needs classes at school, the kids work at a prekindergarten level. “Evie’s like, ‘Why do I have such a hard time reading?’ ” McConnell says. “I’m like, ‘Because you have a metabolic disorder.’ ” Yet when it comes to social and emotional intelligence, it’s Evelyn who often calms McConnell down when she gets stressed. “She’s like, ‘Mom, take a breath.’ ”

Most of the 10,000 rare diseases known to exist, including SSADHD, don’t have effective treatments. Historically, pharmaceutical companies haven’t invested in developing drugs for rare disorders because there aren’t enough potential patients to turn a profit. Instead, parents and patient associations raise millions to fund research themselves, hoping to find potential treatments and attract drug companies with deeper pockets for the necessary clinical trials.

Evelyn and Jack’s diagnoses threw McConnell into a medically disenfranchised community, at the mercy of drug developers that seemed more beholden to investors than to families. “It’s like you’re a beggar,” she says, “begging different companies to help you.” In 2014, a drug company drummed up excitement for a compound it believed might treat SSADHD, convincing the disorder’s patient association to help fund testing on mice. But after too many rodents died, the company “sort of ghosted everyone,” McConnell says. “We had a Facebook page for parents, and you could see all the hope bubbling up, then get crushed.”

McConnell knew she had to act, and that same year, she met Keith Alkek, who worked at Genzyme, a Massachusetts company developing treatments for rare disorders, though not the same type as SSADHD. The two became friends, and over fajitas, they dreamed up Speragen, taking the name from the Latin “spera,” meaning “hope.” They celebrated the company’s launch in an engineless glider: a pilot towed them skyward, and McConnell pulled a cord, setting them aloft.

Over the next five years, with funding from federal grants available to start-ups, Speragen rented space at the Bioscience Incubator, a lab that Austin Community College opened in a former mall. The company hired a lab director and postdoctoral researchers from the University of Texas to test three compounds that had shown promise for treating SSADHD, using tissue samples shipped from Washington State University, which houses a colony of mice with the disorder. The research was directed by K. Michael Gibson, a biochemical geneticist at WSU who, in 1983, confirmed the enzyme defect underlying the symptoms that Jakobs had described two years earlier. “I have never encountered a person with that kind of energy,” Gibson says of McConnell.

A fourth treatment candidate—this one tested in Gibson’s lab—looked especially promising, a pill intended to counteract the effects of too much GABA. Initially developed in the nineties for Alzheimer’s, when it was given to mice and other animals with SSADHD, it improved cognition and reduced seizures. Gibson had already succeeded in reaching a phase II clinical trial on SSADHD patients, making the treatment “a golden goose in the world of pharma,” McConnell says. Since the European company that owned the patent wasn’t interested in developing a drug for SSADHD, it allowed Speragen to license the chemical compound for that purpose, sending a shipment of data on the compound to McConnell’s driveway. It contained eight pallets—weighing roughly a ton—of old documents in need of scanning to prepare for the FDA and potential investors should the clinical trial succeed. “We just laughed, as we could see the immense work ahead of us,” Alkek says.

Between 2014 and 2017, sixteen patients, the majority under the age of eighteen, participated in the phase II clinical trial, including Evelyn and Jack. McConnell noticed that her children’s gait and coordination improved; at the playground, they were able to climb a rope ladder they couldn’t before. But when the results were published, in April 2020, they showed no significant differences between the drug and a placebo regarding the cognition of patients or their abilities to eat, talk, or walk. Speragen’s other three compounds failed before making it to clinical trials. One proved toxic to cells, another couldn’t bind well enough to cell receptors to have any effect, and the third didn’t reduce seizures in mice, as intended.

Reflecting on these setbacks, her long, dark hair falling around her face, McConnell shrugs. Behind her, on the fridge, hang photographs of her children: Evelyn smiling for a school picture; Jack sticking out his tongue. “I’m a giant compartmentalizer,” she says. “I can put being a mom, and how much I love my kids . . . in one box, and I can put the company in another box, and things that go wrong in another box. I couldn’t do this if I let the boxes mix.”

SSADHD has reshaped every facet of McConnell’s life. When she’s shopping at H-E-B or swimming at the pool, strangers shoot dirty looks when her kids make repetitive self-soothing movements or sounds, such as rocking back and forth or loudly humming. At home, they need constant supervision. But McConnell has lived alone with the kids since 2018, when she and her husband divorced, and it was only last August, after Evelyn turned fourteen, that McConnell hired an au pair—a live-in helper for both children—through a federal program that provides visas for workers caring for children. “I don’t know what I’m going to do when Evie ages out,” she says.  For twelve years, the kids have awaited a Medicaid waiver, which would provide in-home care, case management, and other quality-of-life services, but Texas’s program is vastly underfunded and understaffed, and the last time McConnell called, she was told it will be another decade before her children receive benefits.

It’s a lot to handle, but McConnell tries to schedule time away. Twice a week, she teaches ashtanga yoga, which “calms the central nervous system pretty quickly,” she says. She practices Vipassana, a form of meditation that involves detaching yourself from the external world. And she goes mountain climbing every July, when the kids stay with their father. Last summer it was Kilimanjaro. This year, Mont Blanc.

“It takes you out of everything,” she says. “You can’t think about anything else except the next step in front of you.”

The next step for Speragen could be a big one. After the clinical trial of the Alzheimer’s drug failed, Speragen shifted its focus to enzyme replacement therapy, or ERT, which involves injecting a patient with a synthetic version of the enzyme they’re missing. Scientists tested it on mice in 2018, with positive results. Hopeful that ERT might be the answer, McConnell prepared  an application for a federal grant to fund Speragen’s preclinical work for additional studies of the treatment.

Then, out of the blue, a South Korean pharmaceutical company called GC Biopharma came knocking, and Speragen agreed to a partnership in developing the ERT treatment. GC Biopharma would handle the scientific research, while Speragen would do the necessary peripheral work to pave the way for a clinical trial. That has included determining the disorder’s prevalence (with help from Baylor College of Medicine, in Houston, which estimates some 1,500 Americans with the condition remain undiagnosed), collecting insights from patients and caregivers to guide better drug development, and creating a clinical outcome assessment—essentially a report card to be used during a clinical trial to measure changes in participants.

Speragen remains heavily involved, even as GC Biopharma has shifted its research from ERT to mRNA technology, the same thing used for Pfizer and Moderna’s COVID-19 vaccines, which differs from ERT in that it actually tells the body how to make the enzyme it needs. “Better to teach you to fish than give you a fish,” McConnell says. (A team at Boston Children’s Hospital is also developing a gene therapy for the disorder.) In 2023, GC Biopharma constructed a new mRNA plant that Alkek says could manufacture a drug for SSADHD within five years, though it’s still unclear when a clinical trial would happen. (GC Biopharma did not respond to interview requests.)

It will take a lot of work to get there, but meanwhile, Speragen is forging ahead with another of its goals: getting SSADHD screened for at birth. McConnell rarely gets so riled up as when discussing newborn screenings (she even started a YouTube series about them). The rules for what gets screened for were established in the sixties, and they dictate that rare genetic disorders only be tested for if they have existing treatments. Still, Speragen is spending $8.5 million to prepare an application for SSADHD’s inclusion in the national recommendations, suggesting it be listed as a “secondary condition” that could be picked up by an assay that checks for “primary” conditions that already have therapies. The company has plans for a pilot screening program in the fall.

Whether or not those efforts succeed, one thing is certain: McConnell is prepared to keep going. “Most drugs fail,” she says. “If you’re not okay failing, then this is not the thing for you to do.” Behind her tough facade, she experiences disappointment and exhaustion like anyone else, but her friends tell her she just doesn’t react to them the same way other people do. That might be true. Her life isn’t like most other people’s. She can’t let herself ride the highs and lows, she tells me, sitting at her kitchen table, where she often works while the kids eat—something Jack still has trouble with. Like any good parent, McConnell wants her kids’ lives to be as full and rich as possible. She loves them too much to give up.