In one of the most difficult years emotionally in the fight to conquer Huntington’s disease, advocates, scientists, and HD-affected individuals have generated hope as 2021 draws to a close.
The “heartbreaking” news in March about the disappointing results of the greatly anticipated Roche and Wave Life Sciences clinical trials was compounded by the devastating, ongoing coronavirus pandemic.
Last year at this time, leading global HD advocate Charles Sabine, a British former international correspondent for NBC-TV, launched his inspiring film Dancing at the Vatican, about Pope Francis’ embrace of the global HD community, on YouTube.
Like the pope’s 2017 special audience with the HD community in Rome, Dancing at the Vatican brought great hope and joy.
Now Sabine has just released another heartening film, Hoping Machine, a 60-minute documentary that, he says, “encapsulates many core principles” of the pope’s declaration that it is time for HD to be “hidden no more”: the “corrosive nature of denial and hidden secrets” and the “empowerment that springs from knowledge, understanding, collaboration and community.”
“I truly believe Hoping Machine offers the most important perspective that anyone involved in HD right now – researchers, clinicians or families – could hear,” Sabine wrote me by e-mail.
You can watch Hoping Machine for free by clicking on this link.
Powerful HD journeys
Hoping Machine takes its title from the song by American folk music giant Woody Guthrie, who died from HD in 1967, the year his former wife Marjorie founded the Huntington’s Disease Society of America (HDSA).
The film depicts the gripping recollections of HD family members, and also several scientists, of their experiences as keynote speakers at what I have called the “Super Bowl” of HD research, the annual Huntington’s Disease Therapeutics Conference. Beginning in 2006, the conferences are sponsored by CHDI Foundation, Inc., the abundantly funded, nonprofit virtual biotech aimed solely at developing HD therapies.
These speakers have all told powerful stories about their HD journeys, including using the keynote to go public about their HD status for the first time (my case in 2011) and exploring the most intimate and difficult aspects of life with HD.
Inspired by the scientists’ dedication
They have also sought to both inspire and thank the scientists.
“Here I am, affected by Huntington's disease, and I'm relying on all of you guys, all of the scientists, everybody working in the HD community,” keynoter Amy Merkel recalled of her talk in Palm Springs, CA, in February 2020. “I'm relying on you for life.”
Sometimes, when she has experienced symptoms, “I just kinda wanted to crawl under the covers and stop trying,” Merkel continued. “That speech and that time in Palm Springs kind of lifted me a little. You can do this.”
A licensed practical nurse, Merkel had abandoned her “dream” of becoming a registered nurse (RN) “because I knew I was gene-positive” for HD, she said. However, “the advances that all of the scientists have made in Huntington’s research” convinced her to study to become an RN.
Amy achieved her goal: "I'm a registered nurse, and I currently am working as a sexual abuse nurse examiner in southern Arizona."
Amy Merkel poses with researchers Dr. Sarah Tabrizi (far left), Leslie Thompson, Ph.D. (second from right), and Gillian Bates, Ph.D. (far right), at the 15th HD Therapeutics Conference, held in in Palm Springs, CA, February 2020 (photo by Gene Veritas, aka Kenneth P. Serbin).
Good news from the KINECT-HD trial
Another glimmer of hope – and a sign that HD science marches on – came on December 7 with the release of “positive” data from the KINECT-HD phase 3 clinical trial to test the efficacy, safety, and tolerability of Neurocrine Biosciences’ drug valbenazine. The initial trial data demonstrated that valbenazine, as intended, reduced chorea, the involuntary, dance-like movements that are the principal motor symptom of HD.
Marketed by San Diego-based Neurocrine as Ingrezza and already approved by the U.S. Food and Drug Administration (FDA) for the neurological disorder tardive dyskinesia, valbenazine is the same type of drug as the two other FDA-authorized drugs for chorea, Xenazine (2008) and Austedo (2017).
According to the Neuocrine press release, Ingrezza reduced the total motor score (a measure of the severity of chorea) by 3.2 points versus placebo in the trial participants.
This result was very close to reduction of the 2.5 points in Austedo and the 3.5 points in Xenazine.
As the release explained, the total motor score is part of the motor assessment of the research tool known as the Unified Huntington’s Disease Rating Scale (UHDRS®) and “measures chorea in seven different body parts, including the face, oral-buccal-lingual region, trunk and each limb independently.” The total motor score is the sum of the individual scores and ranges from 0 to 28.
Like Xenazine and Austedo, valbenazine is a VMAT2 inhibitor.
Initial data about Austedo (deutetrabenazine) indicated that patients “felt better” overall after taking this drug. In addition, Austedo requires only two daily doses, versus Xenazine’s three (click here to read more).
Ingrezza is even more convenient: the KINECT-HD trial used just one daily dose.
Critical: no suicidal behavior observed
Critically, and also in contrast with the other two drugs, “no suicidal behavior or worsening of suicidal ideation was observed in the valbenazine-treated subjects in this study,” the Neuocrine statement said.
Neocrine partnered in KINECT-HD with the Huntington Study Group (HSG), the leading HD clinical trial administrator and research platform. In a first for the HSG, KINECT-HD trial participants used wearable sensors for continuous monitoring of their movements and other biological functions, even at home. (Click here to read more.)
In 2022, after a complete review of the trial data, Neocrine will report its findings in greater detail at a medical conference, and it will submit the drug for FDA approval for use in HD.
“The positive results of the KINECT-HD study are very exciting for the HD community,” Jody Corey-Bloom, M.D., Ph.D., the director of the HDSA Center of Excellence at the University of California, San Diego, wrote me on e-mail. “Although valbenazine is not a disease-modifying therapy, it will clearly be a highly effective therapeutic option for one of the most common symptoms in HD – chorea.”
“Completing ANY clinical research trial successfully in the midst of the COVID-19 pandemic is cause for excitement, and a testament to the tenacity of HD patients, families, and research teams,” wrote Martha Nance, M.D., the Center of Excellence director at Hennepin Health Care in Minneapolis, MN. “The favorable results are not terribly surprising, since two other similar drugs have been approved previously – but they are certainly reassuring.”
Maintaining the commitment to patients
The “holy grail” for the HD field – and other neurological diseases – is a treatment that prevents people from ever developing symptoms.
Comparing Ingrezza’s success with this bigger challenge, Dr. Nance offered a partial explanation to what she described as a large and complex challenge.
“It only takes a few weeks or months to document that a drug reduces the severity of a symptom (chorea, depression, insomnia), but takes years to show that a drug is slowing the progression of a disease that progresses slowly over years,” she wrote. “We have not gained a toehold on slowing nerve cell loss in any of these conditions.”
However, because the scientists have advanced to attempting treatments aimed at the disease’s roots – DNA and RNA – “there is good reason to hope.”
“Building on the unsuccessful trials that were so disheartening to the global HD community earlier this year, I counted no fewer than thirteen companies moving towards clinical trials of DNA/RNA-directed treatments at our recent HSG research conference in November,” she noted.
Dr. Nance wrote that we should be “thrilled” that 2021 has ended on a favorable research result and “maintain our commitment to work together to find better treatments for the HD patients of the future.”
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