A family in Phoenix is desperately seeking help to afford a
special treatment overseas after two of their daughters were diagnosed with an
aggressive and debilitating brain disease that could ultimately kill them both
Earlier this year, Dave and Kendra Riley's world was flipped
upside down when they discovered that their 2-year-old daughter, Olivia, had a
"highly progressive and rare genetic brain disease" called
Metachromatic Leukodystrophy (MLD), according to a GoFundMe page set up on the
Months later, as Olivia's condition worsened to the point
where she can no longer walk or talk, things became even more heartbreaking for
the family after they welcomed their third daughter, Keira, and learned that
she also has MLD.
As their days with Olivia become "limited," Dave,
Kendra and their eldest daughter Eva, 5, now find themselves in a race against
time to raise enough money by the end of July so that they can afford a special
gene therapy treatment — only available in Milan, Italy — that could
potentially save Keira's life.
"We have so much hope for Keira because of this
treatment and want to do everything we can to give Eva (and ourselves) as many
happy memories as we can with her sisters," the parents wrote on the
GoFundMe. "Please help us raise enough funds to give our Keira the chance
at a normal life; to save her life from the horrible disease that is MLD."
Dave and Kendra Riley. Two of their three daughters, Olivia
(2 years old) and Keira (5 months old), have been diagnosed with Metachromatic
Dave and Kendra first noticed something seemed wrong with
Olivia in November 2019, according to the GoFundMe.
"Olivia began having difficulties walking, would tilt
her head and we then noticed a vibration in the irises of her eye," Kendra
explained. "Concerned, we took her to our pediatrician who suggested
starting PT and going to an ophthalmologist."
The ophthalmologist ordered an MRI, and in the meantime, the
Phoenix parents welcomed their third daughter, whom Kendra said was
"perfectly healthy" at birth on Jan. 9.
But Olivia's condition continued to get worse, and Dave and
Kendra were faced with even more of a challenge in getting her adequate medical
attention due to the coronavirus pandemic.
After finally getting an MRI, which showed "vanishing
white matter in her brain," and seeking out multiple opinions from
neurologists, a genetic test confirmed that Olivia had MLD.
According to the U.S. National Library of Medicine, MLD is a
genetic disorder that affects cells in the nervous system which produce myelin,
the substance that insulates and protects nerves.
The disease causes a progressive loss of brain functions and
motor skills, such as the ability to walk and speak. It also can lead to loss
of sensation in the hands and feet, seizures, paralysis, blindness and hearing
loss and eventually cause one to become unresponsive due to a "lost
awareness of their surroundings."
In Olivia's case, because it presented so early, doctors
have said she is not expected to live past 4 to 6-years-old, according to the
"Dave and I were devastated. How could this happen to
our sweet Livvy?" Kendra wrote, noting that she and Dave even had genetic
testing done before they started having kids and were cleared from MLD.
"Unfortunately, our form of MLD is so rare that they don’t even test for
it, they only test for the five most common mutations."
Kendra and Dave eventually learned that they both carry the
genetic mutation, which presents their kids with a 25 percent chance of
developing MLD, so they immediately had testing done on Keira and Eva.
As they awaited the girls' results, the parents continued to
take weekly trips with Olivia to Iowa, where she has been receiving treatment
and medicine through a port.
"So far, we have not seen a difference but we are
hopeful that it will slow the disease down so we have more time with her,"
Kendra wrote. "Olivia has lost her vocabulary, cannot pronounce most
words, and experiences some form of pain (from moderate to severe) on a daily
By June 19, results confirmed that Eva was a carrier for the
disease like her parents, and will be unaffected by it, but her little sister
had both mutated copies of the gene and MLD, according to the GoFundMe.
"Hearing that not one but two of my daughters’ lives
will be cut short from this awful disease is too much to bare," Kendra
The parents said they immediately reached out to resources
for MLD-affected families after the heartbreaking news and learned of "a
cutting edge treatment option" called gene therapy, which could
potentially give Keira the chance for "a normal life."
Unfortunately, the treatment is only available in Milan, and
because the clinical trial was fully enrolled, Dave and Kendra said they would
have to pay out of pocket for the family to move to Italy for five months.
Additionally, Dave and Kendra explained that if they were to
temporarily move to Europe, they would also have to transfer Olivia's
treatments there and make sure that their insurance will cover them.
"It will cost upwards of $500,000 for the treatment,
lodging, travel and expenses for our girls’ day to day care," Kendra
explained. "This does not include the trips we will need to take back to
Italy every 6 months for Keira’s check-ups. Dave and I will also not be able to
sustain a stable income while we spend this time with our girls."
With no other options, Dave's sister Nina Riley set up the
GoFundMe on behalf of the family on June 25. Since then, they have raised over
$171,000. A tax-deductible fundraising page was also set up on the Armer
Foundation for Kids website.
"Your support will not only help save our daughter’s
life but further the advancement of gene therapy, which has the potential to cure
hundreds of rare diseases," Kendra wrote on the GoFundMe. "We could
not thank you enough for any help or support during this time."
My advocacy for gene therapy dates back to July 5, 2012.
That was the day a neurologist at Children’s Hospital of Philadelphia explained
how my 2-year-old daughter, Cal, had late infantile-onset metachromatic
leukodystrophy (MLD). It is caused by a single faulty gene that she inherited
from both my husband and me. The genetics counselor explained that Cal had won
the worst sort of lottery: MLD affects 1 in 100,000 children.
This genetic error causes fats known as sulfatides to
accumulate in Cal’s cells. As they build up in cells that make myelin, the
substance that insulates and protects nerves, they destroy tissue throughout
the brain, spinal cord, and other parts of the nervous system.
At the time, there was no cure for MLD, and Cal was not
expected to live beyond the age of 6.
A few days after the one-year anniversary of Cal’s
diagnosis, Dr. Alessandra Biffi and her colleagues at the San Raffaele
Scientific Institute in Milan, Italy, published a report in Science magazine
about a revolutionary gene therapy for MLD. Biffi’s team had hoped the therapy
would lead to a milder form of the disease. But some of the children who
underwent the treatment were not developing MLD at all — a miracle to them and
Cal once ran and read books and ate macaroni on her own. By
the time we learned of the Italians’ breakthrough, she had stopped talking,
could not see, and was essentially paralyzed. She gets nourishment through a
feeding tube, and receives hospice care.
To help us cope with our grief, friends and neighbors
started hosting bake sales to raise funds for fighting MLD. The first event
raised $9,000. We weren’t sure what to do with it. Dr. Amy Waldman, Cal’s
neurologist at Children’s Hospital of Philadelphia, made a suggestion that
would change all of our lives. After reading the report by Biffi and her
colleagues, she recommended that we help families get to Milan for the ongoing
MLD gene therapy trial there.
Gene therapy works only to prevent the disease. Once
symptoms appear, it can’t reverse the damage to the brain and central nervous
system. “So how can we help other people’s children when Cal couldn’t be
saved?” I asked Waldman. She explained that, since there is no newborn
screening test for MLD, the birth of a child with the condition is a signal to
test any other children the parents have later. So every child eligible for the
gene therapy trial is a younger sibling of a child living with MLD.
A year later, when Cecelia Price from Omaha, Neb., was diagnosed
with MLD because of her older sister’s diagnosis, the foundation we started was
able to help send her to Milan to take part in the trial. Since then, we have
sent 10 children to Italy: five from the U.S., two from the United Kingdom, one
from Australia, one from Ireland, and one from Switzerland. Some of them now
play baseball and soccer, attend school, and lead remarkably healthy lives.
These children, who have outlived their siblings with MLD, became our
investments in a miracle.
Sessa M, Lorioli L, Fumagalli F, et al. Lentiviral
haemopoietic stem-cell gene therapy in early-onset metachromatic
leukodystrophy: an ad-hoc analysis of a non-randomised, open-label, phase 1/2
trial. Lancet. 2016;388(10043):476-487. doi:10.1016/S0140-6736(16)30374-9
Background: Metachromatic leukodystrophy (a deficiency of
arylsulfatase A [ARSA]) is a fatal demyelinating lysosomal disease with no
approved treatment. We aimed to assess the long-term outcomes in a cohort of
patients with early-onset metachromatic leukodystrophy who underwent
haemopoietic stem-cell gene therapy (HSC-GT).
Methods: This is an ad-hoc analysis of data from an ongoing,
non-randomised, open-label, single-arm phase 1/2 trial, in which we enrolled
patients with a molecular and biochemical diagnosis of metachromatic
leukodystrophy (presymptomatic late-infantile or early-juvenile disease or
early-symptomatic early-juvenile disease) at the Paediatric Clinical Research
Unit, Ospedale San Raffaele, in Milan. Trial participants received HSC-GT,
which consisted of the infusion of autologous HSCs transduced with a lentiviral
vector encoding ARSA cDNA, after exposure-targeted busulfan conditioning. The
primary endpoints of the trial are safety (toxicity, absence of engraftment
failure or delayed haematological reconstitution, and safety of lentiviral
vector-tranduced cell infusion) and efficacy (improvement in Gross Motor
Function Measure [GMFM] score relative to untreated historical controls, and
ARSA activity, 24 months post-treatment) of HSC-GT. For this ad-hoc analysis,
we assessed safety and efficacy outcomes in all patients who had received
treatment and been followed up for at least 18 months post-treatment on June 1,
2015. This trial is registered with ClinicalTrials.gov, number NCT01560182.
Findings: Between April, 2010, and February, 2013, we had
enrolled nine children with a diagnosis of early-onset disease (six had
late-infantile disease, two had early-juvenile disease, and one had early-onset
disease that could not be definitively classified). At the time of analysis all
children had survived, with a median follow-up of 36 months (range 18-54). The
most commonly reported adverse events were cytopenia (reported in all patients)
and mucositis of different grades of severity (in five of nine patients [grade
3 in four of five patients]). No serious adverse events related to the
medicinal product were reported. Stable, sustained engraftment of
gene-corrected HSCs was observed (a median of 60·4% [range 14·0-95·6]
lentiviral vector-positive colony-forming cells across follow-up) and the
engraftment level was stable during follow-up; engraftment determinants included
the duration of absolute neutropenia and the vector copy number of the
medicinal product. A progressive reconstitution of ARSA activity in circulating
haemopoietic cells and in the cerebrospinal fluid was documented in all
patients in association with a reduction of the storage material in peripheral
nerve samples in six of seven patients. Eight patients, seven of whom received
treatment when presymptomatic, had prevention of disease onset or halted
disease progression as per clinical and instrumental assessment, compared with
historical untreated control patients with early-onset disease. GMFM scores for
six patients up to the last follow-up showed that gross motor performance was
similar to that of normally developing children. The extent of benefit appeared
to be influenced by the interval between HSC-GT and the expected time of
disease onset. Treatment resulted in protection from CNS demyelination in eight
patients and, in at least three patients, amelioration of peripheral nervous
system abnormalities, with signs of remyelination at both sites.
Interpretation: Our ad-hoc findings provide preliminary
evidence of safety and therapeutic benefit of HSC-GT in patients with
early-onset metachromatic leukodystrophy who received treatment in the
presymptomatic or very early-symptomatic stage. The results of this trial will
be reported when all 20 patients have achieved 3 years of follow-up.