In today's newsletter: A gene therapy trial has successfully treated Huntington's for the first time - one of several recent groundbreaking medical advances bringing hope in gloomy times
Good morning. Few medical diagnoses are as brutal and devastating as Huntington's disease.
For decades, those who inherited this cruel condition faced only despair. There was no cure. Symptoms began with mood swings and depression, then progressed to a loss of movement, followed by dementia, paralysis and, ultimately, death. Some patients died within a decade of diagnosis.
Finally, a ray of light has burst through. For the first time, Huntington's disease has been treated successfully through gene therapy, slowing the progress of the disease by 75% in patients after three years in a groundbreaking trial.
It is one of several extraordinary medical advances announced in recent months, alongside new possible treatments and diagnostic tests for Alzheimer's, heart disease and stroke.
For today, I spoke with Hannah Devlin, the Guardian's science correspondent, about the exciting research behind this desperately needed good news, and why cuts to scientific research could put future progress at risk. That's after the headlines.
Huntington's disease is a genetic disease that runs through families. It is caused by a single mutation of a gene that makes a protein called huntingtin.
Huntingtin is an essential protein in the brain, but in people who have the mutation, the brain makes a toxic version of it that kills brain cells, Hannah Devlin told me. Between 6,000 and 10,000 people in the UK have the diseases, and another 20,000 are carriers of the faulty gene, which means they are likely to develop it.
"If you've got the gene, you tend to get your first symptoms in the prime of your life - in your 30s and 40s. Then you'll undergo a mental decline, which is a form of dementia, as well as motor issues; including jerky movements, losing your balance and gradually becoming paralysed," Hannah said. "It's a truly devastating condition, and one of the really awful things about it is if you're a gene carrier, your children will have a 50% chance of also having the gene."
Over the last 10 years, Hannah has reported on notable progress in the scientific community's understanding of how the mutant gene causes the disease.
She said: "There has been growing hope that a treatment was on the horizon, but practically, there hasn't been anything for patients. Until now."
A one-off injection
The successful trial used gene therapy to silence the mutant gene so the brain stops producing the toxic protein.
The challenge for researchers was overcoming the blood-brain barrier. "While drugs can flow around the body, the brain has a special barrier that stops that from happening. So getting any treatment into the brain is itself a massive hurdle," Hannah said.
The breakthrough treatment worked by delivering a small piece of genetic material attached to a harmless virus. Scientists infused the virus directly into the brain. Once inside, the virus entered neurons and delivered the genetic material that silences the mutant gene, stopping it from producing the toxic protein.
The procedure is incredibly complex and delicate, Hannah said. "You have to infuse this virus into the brain very slowly, over 12 to 20 hours, through microcatheters put into the two brain areas that are most affected by Huntington's."
She added that this gene therapy unit is remarkable because it is effectively a one-off injection. "So they had the surgery, had this treatment delivered once, and then they were followed up for three years to see whether it altered the progress of the disease."
The research shows that the gene therapy slowed the progress of the disease by 75% in patients after three years.
Ripple of activity
While political leaders appear intent on delivering doom and gloom, the scientific community seems determined to do the opposite.
The breakthrough treatment for Huntington's disease is the latest in a string of remarkable advances, including promising new therapies and diagnostic testing for Alzheimer's, heart disease and stroke.
"We have seen some really exciting developments in Alzheimer's, including the approval of a couple of exciting drugs that could slow progression of the disease. They're not currently funded by the NHS, but it's been seen as a big development," Hannah said.
She also pointed to notable breakthroughs in how Alzheimer's is diagnosed, including a £100 blood test and a three-minute brain scan, which medics hope could transform diagnosis of the devastating condition. These diagnostics could be critical to getting a much faster diagnosis, which is crucial to treating the disease.
"Often when one breakthrough happens, it prompts this ripple of activity and things can suddenly move quite fast in an area where it feels like there was very little progress for years," Hannah told me.
The other big developments recently have been in treatments for heart disease and stroke. Researchers found that a blood-thinning drug could be more effective at preventing heart attacks and stroke than aspirin, which has been the standard for decades.
"A lot of this is off the back of big investments into health research," Hannah said, but that now appears under threat in some corners of the globe.
A bright future, dimmed
The breakthrough in treating Huntington's disease would not have happened without public funding.
"This is work that has been going on for more than a decade at UCL [University College London]. This is an absolutely world-leading team that has benefited from public funding into how to study this awful disease. It's now being fast-tracked in the United States because of this incredible reputation that the FDA [Food and Drug Administration] has with speed and their links with the research community," Hannah said.
But that is now under threat. There have already been major staff layoffs at the FDA, as well as a proposed cut of more than 40% to the National Institutes of Health budget amid what has been called an "assault on science" by the Trump administration. And as I explored in my previous first edition on the impact of US cuts on vaccine research, these decisions will be felt across the world.
"If you fast forward 10 years,some ofthe researchthat'sbeencutwilltranslateintofewer treatments thatcouldhelpwithsomeofthese really awful diseases.Insomecases,researchersarejustonthecuspofbeingabletotreatsomereallydevastatingdiseasessoitdoesfeel depressingthats thesecutsarehappeninginparallel,"Hannahsaid.
Time will tell whether other countries or global institutions step in to fillthegap leftbytheUS.Untilthen,I'llbeheretodeliverthesehappyFirstEditionsonlytemperedbyabitofcautionattheend.
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Our critics' roundup of the best things to watch, read, play and listen to right now
TV
House of Guinness | ★★★★★
The family here is not a crime family: we are in Dublin in 1868, where Guinness is so ubiquitous that the unimaginably wealthy Guinness family run the city. But managing the factory that dominates the landscape is the fearsome Sean Rafferty (James Norton), an arch schemer whose currency is violence. He introduces himself by issuing a rallying call to the company workers, exhorting them to crush an anti-Guinness street protest then leading the way himself, gleefully swinging a hunk of hard factory iron.
Music
Olivia Dean: The Art of Loving | ★★★★☆
Dean’s 2023 debut album, Messy, attracted respectful but mixed reviews and did respectable, rather than remarkable, business. While you wouldn’t describe The Art of Loving as a complete reinvention, it certainly constitutes a noticeable rethink. It expunges most of the cliches of Dean’s debut - or rather quarantines them on a track called Close Up - and instead looks for inspiration to music that emanated from recording studios in 70s LA.
Film
Sane Inside Insanity: The Phenomenon of Rocky Horror | ★★★☆☆
Andreas Zerr’s unofficial documentary charts the 50-year cult of Richard O’Brien’s beloved classic, from its chaotic early days upstairs at the Royal Court theatre. With archival footage and cast, fans and producers among talking heads, it shows how a “shitty fucking movie” became an accidental phenomenon that imitators could never match.
Theatre
Measure for Measure (Royal Shakespeare theatre, Stratford-upon-Avon) | ★★★★★
Emily Burns’s razor-sharp revival cuts away the comic subplots to deliver a tense, streamlined account of Shakespeare’s play about sexual hypocrisy and power. With slick modern dress, a glass-and-chrome set evoking a political battlefield, and a montage of real-world scandals, the parallels with today are stark. Tom Mothersdale’s Angelo is both appalling and human; Isis Hainsworth’s Isabella grows from wide-eyed novice to a mighty force.