A new drug appeared to
slash seizures up to 90% in children with a rare and devastating form of
epilepsy called Dravet syndrome by tackling the underlying genetic
mutation that causes the condition.
The
findings are in an early-stage trial not designed to show efficacy, so
it's not yet clear whether the results will hold up in a larger trial.
But if they do, it would be the first drug with the potential to alter
the trajectory of the disease, which comes with neurodevelopmental
delays and a high risk of sudden death.
"It's one of the first disease-modifying trials for early-onset complex epilepsy such as Dravet syndrome," said study leader Dr. Helen Cross,
a professor of childhood epilepsy at the Institute of Child Health at
University College London and a pediatric neurologist at Great Ormond
Street Hospital.
The results of the clinical trial, published March 4 in The New England Journal Of Medicine,
showed that the drug, called zorevunersen, can safely be given to
children with Dravet syndrome and that it reduces the number of seizures
and improves their overall quality of life.
The
main purpose of this study was to test the drug's safety and find an
optimal dose, but Cross' team also investigated whether the treatment
led to seizure reduction, neurodevelopmental improvements and quality of
life.
"We saw improvements in all those domains, particularly at the higher doses," told Live Science.
Tackling the root cause
Besides
frequent seizures, people with Dravet syndrome also have developmental
delays, coordination problems, behavioral issues and other symptoms. And
around half of the people who have Dravet's will die suddenly and
prematurely due to the disease. These symptoms are all caused by a
problem with interneurons, a type of cell that relays messages in the
central nervous system. Anti-epileptic drugs and implants can reduce the
number of seizures somewhat, but do not improve developmental delays.
A gene called SCN1A controls the
formation of sodium channels that are required for interneuron
signaling. Most people have two copies of this gene, but in many people
with Dravet syndrome, a genetic change stops one of these copies from
working properly. Zorevunersen fixes this problem by increasing the
amount of protein that the other, working copy of the SCN1A gene
produces. The drug is a type of molecule called an antisense
oligonucleotide, and it works by increasing messenger RNA that gives instructions for the working version of the SCN1A proteins.
To
ensure that zorevunersen reaches the brain, it was given as a lumbar
puncture — an injection in the spine that puts the drug into the
cerebrospinal fluid, which bathes the brain. Although treatment required
a visit to the clinic for every dose, the study showed that the effects
last a few months.
A total of 81 children ages 2 to 18 took part in this early stage study
at hospitals in the U.K. and the U.S. Cross and her colleagues were
particularly interested in finding out what dose of zorevunersen would
have the best results, so they tried a few different doses. Some got a
single treatment, while others received a series of lumbar punctures a
few months apart. After this, 75 of the study participants continued to
receive zorevunersen treatment every four months. The participants were
followed for a total of three years.
After 20 months of treatment,
children who received the highest dose at the start of the trial had
between 59% and 91% fewer seizures.
Several
children in the study had mild side effects, such as a headache or
vomiting from the lumbar puncture procedure, or increased levels of
protein in the cerebral spinal fluid. But overall the trial showed that
the drug was safe for children.
The study does have some limitations. It only studied a small group of children, and there was no placebo group.
In
a larger trial that is already underway, researchers are studying an
additional 170 children to find out if those who receive the treatment
indeed show more improvement than a control group.
"We're
targeting the actual underlying cause of the problem," Cross said, "and
therefore, not only reducing seizures but improving other aspects of
the disease."
The trial is
expected to be completed in October 2028, so even if the results are
positive, it will be a few years until this treatment is available to
all children with Dravet syndrome.