A Rare Disease Is Taking His Vision as a Gene Therapy Remains Out of Reach

Judy and Courtney Stecker both worked for the Trump administration, but that did not spare them from a seven-year search for treatment. Wheeler was diagnosed as an infant, early enough to slow a disease that kills brain cells, but he has still not received the therapy. "We are caught in this no-man's-land," Judy Stecker said in an interview.

Wheeler was born with a form of Batten disease. A genetic test before his birth showed that both parents were carriers of CLN3, the most prevalent form of a disorder that prevents cells from clearing waste, causing toxic buildup in the brain. Batten disease robs children of their ability to see, speak, walk or swallow. It affects just a handful of every 100,000 children, but it is the most common form of childhood dementia.

The Steckers had wanted to grow their family. In late 2018, after years of unsuccessful IVF rounds that included two miscarriages, the Steckers unexpectedly became pregnant. Wheeler was born in May 2019 and tested positive for Batten disease at four weeks old. Most families do not learn that a child has Batten disease until about age 5, when vision begins to fail. Wheeler's early diagnosis was crucial for slowing the disease's progress. Many rare disease patients have no potential treatment on the horizon; when Wheeler was born, several drugs were being developed for his condition, including a promising gene therapy from Nationwide Children's Hospital in Ohio.

Gene therapy was then drawing intense excitement. A single infusion can fix misspellings in DNA and potentially cure a wide range of rare genetic diseases. The enthusiasm peaked in 2019 when US regulators approved Zolgensma, a gene therapy for spinal muscular atrophy. At medical meetings, neurologists had tears in their eyes watching videos of children who received the drug and were not only alive but able to walk, according to CNBC. Investors poured money into the field, and Amicus Therapeutics began pursuing multiple gene therapies for Batten disease after acquiring rights from Nationwide Children's.

At the time, no one, including the Steckers, felt comfortable giving a high-risk gene therapy to an infant who was not showing symptoms. Kathrin Meyer, who led the team at Nationwide Children's that developed the therapy, said, "We didn't know anything about the therapy. This kid had a lot to lose." Doctors were optimistic that Wheeler would receive treatment before symptoms appeared. "Unfortunately," Meyer said, "what nobody expected is that everything would stop."

As months passed, the biotech industry confronted the complexity of gene therapy. It requires infusing large quantities of modified viruses to deliver working copies of genes to cells. Some patients died from side effects. Companies struggled to raise enough money to meet the FDA's manufacturing requirements. The market opportunity was often just a few hundred patients, and investors fled.

Amicus also ran into trouble. The gene therapy for CLN3 Batten disease showed promise in the first four children who received it, but the company needed to prove it worked in more patients to win approval. Amicus proposed a late-stage trial with about two dozen children over a two-year period and comparing those results with how other children with the disease usually progress, known as a natural history study. In late 2021, the FDA sent a letter to Amicus saying that was not good enough, according to John Crowley.

Now, a company's talks with the FDA could be Wheeler's last shot at keeping his vision. His case illustrates how patients still fall through the cracks even as scientists make breakthroughs and regulators promise more flexibility. Patients are excluded from clinical trials because of their age or other drugs they are taking. Promising medicines often languish when companies run out of money trying to meet regulatory standards. And when families seek special access to unapproved treatments, they can pose an ethical dilemma for drug companies.