Researching New Therapies: Can We Learn to Set Broken ‘Brain Bones’?

When my son was diagnosed with Angelman syndrome 20 years ago, I believed that we would find a cure. Lou had severe developmental delays and epilepsy. In 2000, the genetic cause of those symptoms was considered an address, not a route to treatment. Few people realized that his diagnosis was the clue, the key to repairing his faulty wiring.

When Lou was 2, we attended his first individualized education program meeting where I requested teaching techniques tailored to Angelman syndrome. His preschool teacher told us, “We don’t care what his genetic diagnosis is, and neither should you. You just need to get used to the idea that he is mentally retarded. We teach all kids with mental retardation the same way.”

The term “mental retardation” was not as jarring back then as it is now. But the message that Lou’s diagnosis didn’t matter persisted for almost two decades.

The difference between compassion and acceptance

Lou struggled to learn his colors and shapes at preschool, and I struggled to learn about molecular biology and developmental psychology. I wanted to help him, and eventually I consulted experts in the field. Most of them responded with a similar message: “Why not accept your son the way he is?” They saw my son’s genetic injury as part of his identity.

Over the years, the term “mental retardation” fell into disregard. As autism has become more commonplace, society has begun to welcome all forms of diversity, including neurodiversity. Acceptance of differences and compassion for those in need are qualities of a wise person and an evolved civilization.

But compassion does not mean complacency. Acknowledging the worth and dignity of an impoverished person does not mean accepting poverty as a permanent condition. Having compassion for an injured person does not mean accepting the injury.

If someone breaks their leg, a doctor sets the bone. Casts, crutches, and wheelchairs help the injured get around until they heal. We don’t leave the bone broken and encourage acceptance of “osteodiversity.” But when it comes to neurological injuries, people confuse the brain, identity, and soul. My son’s injury is considered part of him — part of his personality, part of who he is.

Setting the broken ‘brain bone’

But with new advances in treatments, we might be able to heal this type of injury. Three upcoming clinical trials were announced at the FAST Science Summit, hosted in Chicago by the Foundation for Angelman Syndrome Therapeutics last December.

Enrollment in a Phase 1/2 clinical trial for an antisense oligonucleotide treatment for Angelman syndrome being developed by GeneTx Biotherapeutics and Ultragenyx Pharmaceutical is due to begin in the first half of 2020.

Two other clinical trials of antisense oligonucleotides also are planned to start in 2020 — one sponsored by Roche/Genentech, and the other by Biogen and Ionis Pharmaceuticals.

Other pharmaceutical companies, including Sarepta Therapeutics and StrideBio, are collaborating on the development of gene-based therapies for treating Angelman syndrome and other central nervous system and neuromuscular disorders. Things are beginning to change for genetic brain disorders.

Treatments have eased the effects of Lou’s original genetic injury for 20 years. But now, finally, we may be able to set his broken “brain bone.”

He will still need all kinds of neurological crutches and therapies and wheelchair ramps while his injury heals. Furthermore, the bone may never heal completely, or it may be permanently bent. But the gap in my son’s 15th chromosome, just like a break in a femur, may eventually regrow.

It turns out that the underlying genetic cause of Angelman syndrome wasn’t just an address in the DNA; it was a therapeutic recipe for healing, a combination for the molecular lock.

Continuing progress

Recently, we have been identifying the genetic sources of many neurodevelopmental disorders and picking an increasing number of DNA locks. We need to accept and have compassion for neurodiverse people, just as we need to build accommodations, such as cognitive ramps. But we may no longer need to accept cognitive disability as a permanent condition.

I believe that this year, 2020, could be the watershed moment.

Go science! Go brains!

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