Case study, published in Nature Medicine, details improvements
in nano-rare patient, Susannah’s seizure severity, neurologic
function and quality of life
n-Lorem, a nonprofit foundation, announced today the publication
of a case study detailing the treatment and initial outcomes for a
nano-rare patient who is receiving treatment with a personalized
experimental ASO medicine discovered and developed specifically for
that patient. In this report, most outcome measures including
seizure severity, number of falls, overall speech and quality of
life improved after treatment. The study, authored by the patient’s
doctors Wendy K. Chung, M.D., Ph.D., of Boston Children’s Hospital,
and Jennifer M. Bain, M.D., Ph.D. of Columbia University Irving
Medical Center, along with n-Lorem, was published today in Nature
Medicine (Zeigler, A., et al. Nature Medicine advanced online
publication, Aug 2024).
In this study, the challenges caused by KIF1A-associated
neurological disorder (KAND), and the positive impact observed
during treatment on Susannah’s neurologic function and quality of
life were described. The case study reported that during the 50-day
period prior to treatment, Susannah’s parents described 100 and 290
seizures a day. Following her first dose of the personalized
experimental ASO medicine developed by n-Lorem, her parents
reported the number of seizures dropped to less than 30 a week,
where it remained relatively consistent. Similarly, prior to her
first dose, Susannah’s ability to walk was severely impaired with
an average of 26.2 falls a day. A month after her first dose, her
gait improved and the number of falls decreased to a maximum of
seven a day, while many days she didn’t fall at all despite being
far more active. In addition, researchers noted improvements in her
quality of speech, attention level, engagement, ability to interact
in group activities and motor function while her cognitive ability
remained stable. The patient has now been on ASO treatment for 20
months with a favorable safety and tolerability profile.
“Our goal from the outset with Susannah was to arrest the
progression of her disease, which is often fatal. This is the first
time a medicine has been able to treat the genetic cause of KAND,
halt disease progression and provide meaningful clinical benefit,”
said Wendy Chung, M.D., Ph.D., Chair of Pediatrics at Boston
Children’s Hospital. “While Susannah’s medicine was designed to
work on her specific genetic sequence, we are hopeful that more
KAND patients will potentially benefit from this medicine. Our
KOALA study is important in this endeavor, as it allows us to
evaluate each patient’s clinical status and genetic sequence to
identify which patients may potentially be candidates for this
medicine.”
“n-Lorem’s approach is truly personalized medicine, where an
individual patient’s genetic profile is used to guide treatment of
that patient’s disease. In this case, n-Lorem’s ASO was designed to
target Susannah’s specific genetic cause of disease in hopes of
halting the progression of her neurodegenerative disease,” said
Jennifer M. Bain, M.D., Ph.D. Associate Professor of Neurology and
Pediatrics at Columbia University Vagelos College of Physicians and
Surgeons. “Since starting the treatment, Susannah has made
improvements far beyond what we expected. We have been able to
track how she has advanced from using a wheelchair much of the day
to walking, climbing stairs and even playing basketball with her
brother. We are hopeful that what we are learning from Susannah can
apply to other KAND patients.”
KAND is a severe neurodevelopmental and neurodegenerative
disorder that is often fatal and can cause irreversible brain and
optical nerve atrophy, epilepsy, cognitive impairment and
peripheral neuropathy. The disorder is caused by more than 100
mutations in KIF1A, and KAND will require multiple ASOs to treat
all KAND patients. In an effort to understand how KAND symptoms
develop and change over time, Dr. Wendy Chung’s team is conducting
the KOALA study (KIF1A Outcome measures, Assessments, Longitudinal
And endpoints study) to advance KAND research by performing
longitudinal standardized assessments with KAND patients.
“We are beyond thrilled with the improvements that we have
observed in Susannah. Prior to treatment, Susannah’s disease had
progressed to her being mostly in a wheelchair, approaching
nonverbal with debilitating seizures that limited her and her
family’s quality of life. Susannah has now been on treatment for
more than 20 months and we continue to observe improvements in her
mobility, neurological function and quality of life,” said Stanley
T. Crooke, M.D., Ph.D., Founder, Chairman and CEO, n-Lorem
Foundation.
“Because the KIF1A protein serves a vital function in the body,
our approach required the design of an ASO medicine that would
target the copy of the gene that had the mutation, while allowing
the other copy of the gene that does not contain the mutation to
produce normal KIF1A protein. This selective gene targeting of the
ASO allows the functional KIF1A protein to be expressed and
available for normal cellular function, while removing the toxic
KIF1A protein. There is no other technology that is capable of this
gene selectivity, only ASO technology,” continued Dr. Crooke.
“While we hope to see such dramatic improvements in all of our
patients, we understand that may not be the case given the broad
diversity of target genes, disease progression and disease severity
in our patients.”
n-Lorem discovered and developed a personalized, experimental
ASO medicine specific to Susannah’s needs. The first dose was
administered in October 2022 by Drs Chung and Bain at Columbia
University Irving Medical Center. Susannah remains on treatment at
Columbia Medical Center and continues to see increased clinical
benefit from this medication.
“Personalized ASO medicines can be incredibly selective and
offer significant therapeutic hope for many nano-rare patients. At
n-Lorem, we believe that each patient deserves the very best ASO
that we can discover, and we have the expertise, knowledge,
automation and experience to do just that for our nano-rare
patients,” concluded Dr. Crooke. “While we are treating one
nano-rare patient at a time, what we are learning from a single
patient will help entire patient communities and broaden our
understanding of how a single gene mutation can cause devastating
diseases. We built n-Lorem knowing that one day we might be
treating thousands of nano-rare patients.”
To learn more about Susannah’s story see n-Lorem website, watch
this video created after she started receiving treatment or listen
to Susannah’s Journey podcast on the n-Lorem Patient Empowerment
Program.
About n-Lorem
n-Lorem Foundation is a non-profit organization established to
apply the efficiency, versatility and specificity of antisense
technology to charitably provide experimental antisense
oligonucleotide (ASO) medicines to treat nano-rare patients
diagnosed with diseases that are the result of a single genetic
defect unique to only one or very few individuals. Nano-rare
patients describe a very small group of patients (1-30 worldwide)
who, because of their small numbers, have few if any treatment
options. n-Lorem Foundation was created to provide hope to these
nano-rare patients by developing individualized ASO medicines,
which are short strands of modified DNA that can specifically
target the transcripts of a defective gene to correct the
abnormality. The advantage of experimental ASO medicines is that
they can be developed rapidly, inexpensively and are highly
specific. To date, n-Lorem received over 280 applications for
treatment with more than 130 nano-rare patients approved. n-Lorem
was founded by Stanley T. Crooke, M.D., Ph.D., former chairman and
CEO of Ionis Pharmaceuticals, who founded Ionis Pharmaceuticals in
1989 and, through his vision and leadership, established the
company as the leader in RNA-targeted therapeutics. Follow us on
Twitter, Facebook, LinkedIn and YouTube.
To learn more about n-Lorem’s mission at www.nlorem.org, and
please consider giving to n-Lorem to bring hope, possibility and
treatment options to these patients and families in need.
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version on businesswire.com: https://www.businesswire.com/news/home/20240808946685/en/
n-Lorem: Amy Williford, Ph.D. Sr. Director of
Communications amy.williford@nlorem.org