'Too Rare to Care'? A New Center in Boston Wants to Change That

Every week, a scientist named David Liu gets at least 20 desperate messages from parents. Each parent has a child with a rare and serious disease caused by a broken gene, and they want to know if Liu can help build a treatment. Liu works at the Broad Institute in Boston, and he has to give them hard news: the science to fix these genes exists, but the system to turn that science into real medicine is too slow and too expensive. A single treatment can take years and hundreds of millions of dollars to develop.

Because so few people have these rare diseases, drug companies do not think it is worth the cost to make treatments for them. The catchphrase doctors use for this problem is 'too rare to care.' Dr. Wendy Chung of Boston Children's Hospital says that phrase sums up a real and painful pattern: children suffer and die because no company sees enough profit in helping them.

Now, Liu, Chung, and their colleagues want to break that pattern. On Tuesday, they announced a new nonprofit organization called the Center for Therapeutic Genetics. It brings together scientists from the Broad Institute, Boston Children's Hospital, and the Jackson Laboratory to create gene therapies that can be used again and again for many different diseases. The idea is to treat these therapies more like a standard procedure than a brand-new drug.

Researchers would build one basic system for editing genes, then swap out just the instructions for each new disease. That way, they would not have to start from scratch every time. Liu says this approach could eventually help millions of people. Around 400 million people worldwide live with a rare disease, and about half of them are children — one-third of whom die before they turn 5.

The center is starting with $34.5 million from a federal agency called the Advanced Research Projects Agency for Health, which funds bold and high-risk medical research. Scientists will begin by focusing on rare brain diseases that cause seizures. They hope to show that one gene-editing system can work for many different brain conditions, including diseases that affect adults, like Huntington's disease.

The first disease they will target is called alternating hemiplegia of childhood, or AHC, which affects only about 400 children in the United States. One of those children is 10-year-old Annabel Frost, who lives in Washington, D.C. with her parents. When Annabel was just 2 months old, she began having seizure-like episodes and periods of paralysis where her whole body would stop moving, sometimes for a week at a time. Her parents traveled across the country looking for answers, but no doctor could explain what was wrong.

After finally getting an AHC diagnosis, the Frosts learned there was no cure. They started their own nonprofit and spent eight years raising more than $4 million. Dr. Chung says asking sick children's parents to run fundraisers and organize charity races is 'very unfair,' and even then, the money raised is almost never enough to get a company interested in building a treatment.

Instead of just asking Liu to solve the problem, the Frosts spent years funding research that built a strong scientific foundation for a possible gene therapy. Nina Frost said, 'We did not simply bring David a disease and ask him to solve it. We brought him a developed scientific opportunity.' Liu's team had already had success using gene editing to extend the lives of mice with a genetic brain disease called Niemann-Pick, which gave everyone hope.

One big challenge is getting a gene editor into a human brain. In mice, scientists can simply inject it directly. That does not work in people, because the brain is protected by something called the blood-brain barrier — a tough membrane that keeps out germs and toxins, but also keeps out many medicines. Researchers at the Broad Institute found a clever solution: they can use a carrier protein the body already uses to deliver iron to the brain, letting an engineered virus hitch a ride.

The treatment would work like this: a patient receives an injection into a vein. The engineered virus travels through the bloodstream, crosses the blood-brain barrier, and enters the brain. Once inside brain cells, the gene editor slides along the DNA until it finds the broken gene and then corrects it. Team member Dr. Timothy Yu called that discovery 'a real lightbulb moment.'

The center will also use its approach to treat Dravet syndrome, a serious form of childhood epilepsy that occurs in about 1 in every 15,700 births. Twenty percent of children with Dravet die before they turn 18, often in their sleep. Mary Anne Meskis, the CEO of the Dravet Syndrome Foundation, described the fear that parents live with every night. Her own son, Elliot, had his first seizure at 6 months old — it lasted a full hour before doctors could stop it.

Elliot was 4 years old before doctors figured out he had Dravet syndrome. He now takes several medications each day, but he functions at the level of a 3- to 5-year-old and cannot speak in full sentences. Scientists have already corrected Dravet in mice using gene editing and are now preparing to try it in humans. Doctors hope the therapy could help or even cure younger children who are treated early.

The center's founders plan to share their methods publicly so that other doctors around the world can use their tools for their own patients. Dr. Mark Kay of Stanford University praised that plan, saying sharing research is something for-profit companies rarely do, but that it is exactly what is needed to make real progress. Dr. Chung summed up the urgency: 'My patients don't have time to wait. We will lose a generation.'