In a panel moderated by Charles Hart, PhD, the director of the Small Molecule Discovery Center and an adjunct professor in the Department of Pharmaceutical Chemistry at UCSF, experts gave people in the rare disease world reason for hope—along with a description of some of the steeper challenges.

Aaron Tward, MD, PhD, a head and neck surgeon at UCSF and associate vice president for gene therapy at Eli Lilly, said that genetic hearing loss has developed as a promising area for treatments. As many as 200 different genes may cause genetic hearing loss, he said, so scientists are looking to find the right delivery vehicle, such as a virus, to replace the gene and restore hearing.

Clinical trials are underway, Tward said, including at UCSF, and some patients are responding positively.

Another panelist, Fyodor Urnov, a professor of molecular therapeutics at UC Berkeley and director of therapeutic research and development at its Innovative Genomics Institute, complained about the FDA’s cumbersome rules that hinder rare disease research.

If a child is born with a new mutation, Urnov said, the treatment could be addressed with the gene-editing tool CRISPR, but federal regulators may demand an entirely new trial—even though the procedure would only require single small change from what had already been approved.

Urnov described a patient at UCSF, a 26-month-old boy, who was diagnosed with a rare disease and died 42 days later. “I can build that kid a CRISPR in 42 days to repair that mutation,” Urnov said, noting that 50 other labs in America could do the same thing. “But in the olden world, it takes three years and $50 million to do that, by which point, of course, your child died two years and 11 months ago.”

He offered a simple analogy.

“When you go to buy a pizza, when you change toppings, they don't rebuild the oven,” Urnov said. “They don't recertify the dough. They don't recertify the cheese. They just change the toppings. But the olden system means you change the topping. You recertify the oven.”

Reasons for Hope

Urnov noted that the regulators are listening to the scientists. Progress has been made. The FDA has granted permission for a “master clinical protocol” for children with HLH, hemophagocytic lymphohistiocytosis, a severe hyperinflammatory syndrome.

“It doesn’t matter which mutation in which of the six genes that cause the syndrome the child has… they are under the master protocol, which is an unprecedented development in my 26 years,” he said.

His ultimate advice to scientists seeking FDA approval: “Be aggressive. Be bold in dealing with the agency.”

Tward echoed Urnov’s sentiments, noting that “we have a model from the world of surgery.”

“If I want to do a new surgery that’s never been done before, there’s nobody to stop me,” Tward said. “I have an informed discussion with the patient. I tell the patient: ‘Here are the risks and benefits.’”

A similar model could work wonders in treating rare diseases, he said. “We need a new medical specialty of bespoke therapies,” he said.

The two offered complementary takes on one other topic. “Folks, we have to stop using the words ‘rare disease,’” Urnov said. By putting every disease into its own bucket, people are divided, when they should be coming together to advocate for their common interest—such as the need for the platform-based model he described.

Tward noted that medical science is continually drawing distinctions between different variations of the same condition. “Everything we’re calling a common disease is being divided more and more and becoming a rare disease,” he said.