Like many affected by Huntington’s disease, renowned British journalist Charlotte Raven longed for the chance to participate in a clinical trial of a potential treatment for the incurable disorder.
Charlotte was diagnosed with Huntington’s in 2005. She inherited the genetic mutation from her father, who, after a long battle, died from HD in 2016.
In 2019 Charlotte had her wish fulfilled in London. As part of its HD clinical trial program to evaluate the efficacy of tominersen – the historic first attempt to attack the disease at its genetic roots – the pharmaceutical giant Roche was recruiting volunteers for GEN-PEAK, a small, Phase 1 study run in tandem with the larger, main, Phase 3 study.
Charlotte became “patient 1,” the first individual in GEN-PEAK to receive tominersen. If successful, the main trial would result in all participants in the program, including GEN-PEAK volunteers, receiving the treatment.
In her keynote speech at the recent 17th Annual HD Therapeutics Conference, Charlotte recalled the immense hope she felt about tominersen, shared by HD families around the globe: “Ever since I’d been picked to be on the trial, I’d woken up every morning thinking about the drug. It was like being in love. It was what I needed, wanted, looked forward to.”
A heartrending presentation
Those hopes were dashed on March 22, 2021, with Roche’s announcement that it was halting dosing of tominersen because of unfavorable efficacy data.
“Now that pinprick of light had been blacked out,” Charlotte told the 300 researchers, biopharma executives, and advocates gathered at the conference, held in Palm Springs, CA, and sponsored by CHDI Foundation, the nonprofit virtual biotech firm dedicated to developing HD therapies. “The world ended again; it felt exactly the same as the moment of my original diagnosis.”
Struggling with HD symptoms and assisted by her twelve-year-old son John, Charlotte bravely delivered a heartrending presentation, reading from a computer screen. Because Charlotte’s speech is slurred, the audience was provided access to an online script. She received a standing ovation.
Despite the bad news of 2021, drug hunters expressed renewed optimism about potential therapies. As reported in my previous article, the ensuing three days of scientific talks focused on multiple approaches. Indeed, Roche said it would test tominersen again in an improved clinical trial.
Assisted by son John, Charlotte delivers her keynote address (photo by Gene Veritas, aka Kenneth P. Serbin).
‘Feeling your personality crumble’
Charlotte’s keynote traced her career as an ambitious and controversial journalist and social commentator, her family’s fight against HD, and her efforts to cope with the symptoms and resulting limitations on her work and life.
The speech echoed Charlotte’s book Patient 1: Forgetting and Finding Myself, published last November. CHDI gave each conference attendee a copy.
In Patient 1, Charlotte provides a detailed, hauntingly beautiful portrait of the challenges posed by HD to both her and her extended family. Writing with help from her brother Daniel, as yet untested for the mutation, Charlotte intimately describes the toll HD has taken on her, robbing her of her memories and producing crippling anxiety.
“I wanted this book to be an accurate record of what it is like to exist with HD and to feel your brain and personality crumble,” Charlotte writes.
It also includes the first published account of the Roche program from a patient perspective.
‘A new leaf of hope’
During her CHDI keynote, to rest, Charlotte took two short breaks.
In the first interlude, with Charlotte looking on, her daughter Anna, 17, took the stage to speak of the special bond she has developed with her mother because of HD.
“Growing up under the shadow of Huntington’s has meant I’m often not the only priority, and sacrifices need to be made to make sure that my mom is properly looked after,” said Anna, who helps care for her mother.
Untested, both Anna and John have a 50-50 chance of inheriting the HD mutation. HD genetic testing protocols recommend against testing before age 18.
“Seeing and hearing about all these people working and researching to find treatments amazes me every day and makes everything seem a little less bleak,” Anna said. “The future for me, my brother, and my mom is unknown, but we have a new leaf of hope, and for that I would like to say thank you from the bottom of my heart.”
In the second interlude, Charlotte’s neurologist and clinical trial physician, Ed Wild, M.D., Ph.D., described her intellectual mettle. Dr. Wild wrote the Afterword to Patient 1. At the conference, he also recalled how “injecting 120 milligrams of tominersen into Charlotte’s spine in 2019” was one of his “proudest moments” in his career of helping HD patients.
Watch the entire keynote presentation in the video
below, which includes the option of closed captioning.
The best team for defeating HD
Charlotte finished the speech with a tribute to researchers and a reflection on how confronting HD has “humbled me, and helped me connect more with the people around me, which is a new skill that I’ve been working on with commitment and persistence.”
“GEN-PEAK may have turned out to be a blind alley, but it was still a step on the journey towards a cure, and I still feel proud to have been part of it,” she said. “I’ve lived a fairly selfish life in lots of ways, so it seems oddly fitting that this last thing I did to save myself, might end up saving others instead.”
Charlotte noted an irony: she could write Patient 1, with its portrayal of HD's impact, only because the disease had mentally “compromised” her.
“I feel like I’ve finally been able to portray my family and friends as they really are instead of as I’d like them to be,” she added. “They are coming to life.”
She concluded: “Anna and I cannot get over how HD is such a rare disease, yet somehow attracts so many of the world’s brightest and best scientists. In my complicated journey with empathy, this is the most striking gift I can imagine.”
