Scientists gaining ground of Huntington’s
Important new developments mark progress in fight against Huntington’s disease
A
flurry of research findings and an eagerly
anticipated clinical trial now underway suggest
scientists might be on the verge of giving
Huntington’s disease patients something to cheer
about. But while progress is being made, there is still a
long way to go.
The progressive neurodegenerative disorder is
caused by a mutant gene, called huntingtin, that is
inherited from a parent. There is a 50-50 chance of a
parent who carries the gene passing it on to the next
generation.
Symptoms of Huntington’s typically begin in
a patient’s thirties or forties, with irritability and
depression typically followed by tremors and
reduced coordination. Patients eventually lose the
ability to walk, speak, and swallow. They undergo
personality changes and withered cognitive function.
Death generally comes 15 to 20 years after the first
symptoms.
A long-awaited placebo-controlled trial has just
begun that will assess the efficacy and safety of
RG6042, an investigative antisense oligonucleotide.
The drug is designed to target and destroy all forms
of mutant huntingtin proteins, potentially delaying or
halting disease progression. Current therapies only
help manage disease symptoms.
The trial of 900 subjects in 101 global locations,
sponsored by Hoffmann-La Roche, is due for
completion in August 2022.
In the lab, findings have been coming in regularly
over the last two years, most recently with a Duke
University team identifying a new function of
huntingtin. Addressing the gene’s role in maintaining
the neural connections in the brain area involved in
controlling movement may provide a new avenue
against Huntington’s, the researchers believe.
In a separate study in New Zealand, a human brain
bank two years ago pinpointed an early biochemical
change in the brain that results in Huntington’s, raising
the potential for targeted treatment one day.
“There’s been a lot of hope and a little bit of hype,”
Dr Anthony Hannan, head of the Epigenetics and
Neural Plasticity Laboratory at the Florey Institute of
Neuroscience and Mental Health in Australia, told
Global Health Asia-Pacific.
In 2018, a team under Professor Hannan found
dramatic differences in gut bacteria between healthy
mice and mice genetically engineered to develop
Huntington’s as they age. The research points to
the urgent need for follow-up studies in humans
to validate the findings. It also provides even more
evidence that the gut plays a significant role in
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diseases of the brain.
Professor Hannan speculates that the wave of
recent findings might have been spurred on by a
combination of greater funding from philanthropy,
more governments supporting drug studies into
orphan diseases, and drug companies becoming more
interested in developing treatments for Huntington’s.
“Roche and others have been getting involved in
Huntington’s when 10 years ago they weren’t,” he
said. “They might have realised that, even though it’s
not a common disease, if they can prove themselves
through Huntington’s, they can take these therapies
into other diseases.”
Currently, only therapies that slow down the
progression of Huntington’s exist. The Roche trial
still has a way to go, as do other clinical tests that are
under way.
“I’d like to see some more phase 2 and 3 data
before wanting to give Huntington’s families false
hope,” Professor Hannan said.
MARCH 2020
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