Medical challenges: When a cure comes too late

By Daniela J Lamas

NEW YORK: Tyler Parish thinks of himself as “the last dinosaur.” If he had been born decades earlier with the same genes, he would not have had access to the medical care and technology that allowed him to see his 43rd birthday. But if he were born today with access to gene therapy for spinal muscular atrophy, he might have been able to walk without assistance. He might have been able to live a life without fear of impending medical catastrophe. He would likely not be in a long-term care hospital in Boston, with a team of doctors trying to decide whether he needs a tracheostomy tube and a ventilator at night for the rest of his life.

The way Parish sees it, the life he has lived will one day become something of a historical curiosity. His experience of S.M.A., with all the suffering it has entailed, will likely be rendered extinct. Gene therapy has seen remarkable and highly publicized success in recent months, from the Food and Drug Administration’s approval of what amounts to cures for sickle cell disease to the news that a boy with congenital deafness could hear for the first time in his life following gene therapy.

These stories are, unsurprisingly, the ones in the headlines. But as science moves forward, there are an increasing number of people like Parish. There are life-changing treatments available for his disease, but they seemingly cannot reverse the damage that has already been done. A growing population of patients is faced with a challenging question: What is it like for those who know that their disease could be cured or significantly managed within their lifetime but that they won’t be able to — or might choose not to — see that benefit? “When I talk as someone who is older, who is ‘missing out’ on some of these things, it’s not from a bitter place. It’s from a place of, ‘Thank God that these younger people are born at the right moment in time,’” Parish told me. “I love the idea that a kid can be born with S.M.A. and never know the desperate medical situations, the social situations they’re going to be able to avoid.”

Parish spoke to me with the aid of a “speaking valve” on his tracheotomy tube, pausing every now and again to move his head backward, which was a more comfortable position for him given the severe curve in his spine. He had initially been admitted to a hospital in Miami, where he lives part-time. Pneumonia led to the need for a breathing tube and an urgent transfer to a hospital in Boston for the tracheotomy. From there, he had been transferred to the long-term hospital, where he was briefly my patient. He had already learned to adapt to so much — the power wheelchair, the inability to turn himself in bed — but this would be something new. The possibility of a ventilator at home at night would mean eight hours without his voice. It scared him.

It is a strange time for Parish to face his most life-threatening medical catastrophe, just as modern medicine offers hope for children born with his disease. When he was growing up, in the 1980s and 1990s, there was no talk of gene therapy. The doctors had told his mother to take him home and love him. His nerve cells would die, his muscles would atrophy and he likely would not live beyond his second birthday. It was one of the first things he learned about himself: that he had a disease that would shorten his life. This knowledge made him hungry to experience all he could in whatever time he had, to feel alive and free even within the confines of his body. After a wild youth, he began to look toward the future and realize that perhaps he could live longer than he had thought. He began to hope for things like a house, maybe even a family, a career as an artist.

And then, about a decade ago, Parish’s health started to decline. Breathing became harder. He began to wonder if this was it — whether he was reaching his “final chapter.” Grasping at any hope he could find, he saved money to raise funds to take part in a gene therapy trial in China. But then he started to contemplate the plethora of unknowns that could be even worse than his known reality. And so he gave up the effort. He would focus on his health so that when doctors were able to offer a more proven treatment that could act on his faulty genes, he would be ready.

When the doctors first told him about a drug called nusinersen (marketed as Spinraza) back in 2016, he felt like he won the lottery. This is what he was waiting for. A drug, injected directly into his spinal column, to act on the nerve cells in his spine and help improve the underlying cause of his muscle weakness. The positioning would be complicated given his twisted spine, but Parish knew that his condition was worsening. His muscles were getting weaker. He found himself fatigued even when eating. This time, it was worth the risk.

The treatment wasn’t the dramatic thing that he had hoped for. He didn’t see the clouds part and the sun come through. But as the months passed, he started to realize that his arms weren’t getting so tired when he was eating. He still could not turn himself in bed. But maybe things were a little bit better — or at least had stopped getting worse. Now he takes an oral drug that spares him the spinal taps. He thinks of these treatments as a “bridge,” something that keeps him as stable as possible until the next medical advance.

This might be the story for those like Parish, who have lived their lives with genetic disease and are only now seeing the beginning of potentially transformative treatment. The sickle cell experience is remarkable, but that is not the way it will be for every disease, not right now. It might not be about a cure, but instead about slight improvement or plateau. For some, it is about participating in a trial that brings us closer to the answer but is just a step on the way. It’s about seeing the next therapy hit the market and knowing that you will not be able to benefit. But that the future generation will.

When it comes to S.M.A., a disease that causes physical suffering and can lead to an early death, whether to undergo gene therapy has little ethical ambiguity. There is now a one-time therapy that completely replaces the missing or malfunctioning gene and is approved for children under 2 years old, before much of the damage from the disease has set in. But for those who are older, with other, possibly less devastating diseases, and who have lived their entire lives within a community united by shared health challenges, there are real questions about what is lost when a disease is cured. Where is the line between pathology and human variability, and who gets to decide which diseases need fixing?