Families travel long, hard road to find answers for rare diseases

Monica Coenraads had a terrible feeling something was wrong with her 14-month-old baby, Chelsea. She had not learned to walk. She had one word, "duck," and then lost it.

Coenraads was determined to find out why. It What happened upended her life. Chelsea, it turned out, had Rett syndrome.

It's one of about 7,000 rare or orphan diseases — defined as an illness that affects fewer than 200,000 people nationwide. Ninety-five percent of them have no known therapies. They are overlooked by most scientists, and some illnesses may be untreatable, even if they are understood.

Coenraads, 57, who lives in Trumbull, Conn., has encouraged research into Rett syndrome where there had been none. When frantic parents of children with other rare disorders call, Coenraads recognizes the fear in their voices. "We have no choice," she said. "We are desperate parents. We have children with horrible diseases."

What follows are the stories of the Coenraads and three people who have succeeded against the odds in promoting research on rare diseases.

The Coenraads had never heard of Rett syndrome when they received Chelsea's diagnosis at age 2. It is a neurological disorder caused by a mutated gene that destroys a child's abilities to walk, talk, eat and even breathe easily. There was no treatment, no cure.

Coenraads started the Rett syndrome Research Trust, raising $70 million. But money was not enough.

"You have to get up to speed on the science," she said. "You have to learn the basics of drug development and how to recruit scientists and companies to work on your disease."

One scientist, Sir Adrian Bird at the University of Edinburgh, described her work: "For what started as a tiny charity to inspire world-class research on a disorder that initially languished in obscurity and ignorance, and take it all the way to the brink of clinical application in less than 20 years is an amazing achievement."

The journey of Sonia Vallabh, 36, and her husband, Eric Minikel, began in December 2011. She had graduated from Harvard Law School a year after her mother died at 52 from Gerstmann-Sträussler-Scheinker syndrome, a uniformly fatal brain disease caused by misfolded prion proteins. It is estimated that no more than 10 out of every 100 million people have GSS.

Vallabh, who also will develop GSS, and her husband realized they didn't understand the disease enough to ask the right questions. So they became scientists.

She started night classes in molecular biology, biochemistry, cell biology and genetics at the Harvard Extension School and audited courses at MIT.

Then she got a job as a research technician at Massachusetts General Hospital, quitting her day job as a lawyer. Her husband, an urban planner with a degree from MIT, soon followed, starting a position there in bioinformatics.

Soon they wanted to study prion diseases, so they enrolled as Ph.D. students at Harvard.

For common diseases, companies do the preliminary work. But with rare diseases, "the burden shifts," she said.

Vallabh and Minikel had to develop a test to show the drug was working, do studies showing the treatment changed the disease's course and sign up research participants. That recruitment was suspended in March because of coronavirus.

Neena Nizar, 42, grew up in Dubai, United Arab Emirates. She was told she had rickets, then that she had polio.

What she has is Jansen's metaphyseal chondrodysplasia, a genetic disease so rare only about 30 cases have been reported since 1970. Patients have deformed bones, short limbs, small hands with clubbed fingers and dwarfism.

Her search for a diagnosis began when she realized her sons, 11 and 9, shared her affliction. "I sent X-rays around the world of my kids and myself," said Nizar, who lives in Elkhorn, Neb. "No one knew what it was."

But a pediatric geneticist in India, Dr. Sheela Nampoothiri, recognized it, remembering a slide in a medical school. The professor said he was going to skip that slide, the doctor told Nizar, explaining to students that "you will never see this."

Dr. Harald Jueppner, a pediatric nephrologist, was the researcher who first identified the mutation that caused the condition. He had been studying the mutated gene, called a PTH/PTHrP receptor, for 20 years out of scientific interest. But he had never seen a patient. She told him he could now see three.

The FDA requires preclinical data before testing in patients would be allowed. But the lab is only now slowly reopening after the coronavirus forced it to shut.

Matt Wilsey, 42, a tech entrepreneur and investor, had an array of friends in Silicon Valley. But he never thought he'd have to use his business savvy to try to save his child.

His daughter Grace did not sit up, or crawl. She did not learn to walk or talk.

When she was 3, Matt and his wife, Kristen, found out Grace had a genetic disorder so rare only one other child in the world, a boy in Utah, was known to have it. It was caused by a mutation in a gene, NGLY1.

Matt Wilsey started a foundation and raised $9 million. He contacted scientific luminaries, asking if they would work on the project. Carolyn Bertozzi, a chemist at Stanford, was one of his initial recruits. "Imagine you are a parent," she said. "No one had ever had this diagnosis before, and you have no idea what to expect."

Wilsey recruited about 150 scientists as advisers.

The scientific team finally figured out that the mutated gene controls the way other genes function. Now they hope to develop a treatment for the growing number of identified NGLY1 patients, now up to 70.

Wilsey knows the disease seems to accelerate once children hit puberty. "That's a constant reminder that the clock is ticking."