After 17 years of estrangement
because of disagreements over family caregiving, in July I visited my hometown
in Lake County, Ohio, to reconnect with my younger sister Donna. She began having Huntington’s disease symptoms
in 2020.
In early 2023, Donna told me, via Facebook,
that she had tested positive for HD but did not mention whether she had
symptoms. I did not respond at that time because of unforeseen circumstances
unrelated to HD that led me to step back from HD advocacy, including this blog.
In March of this year, I finally
responded to my sister, my only sibling. We then spoke on the phone. Donna
explained that she had HD symptoms. Despite her HD, we had an understandable
conversation. She also revealed that one of her three sons, 37-year-old Greg,
had also tested positive for the HD gene.
At the end of this emotional phone
call, we expressed our love for each other and our respective families. I felt
an enormous relief at having reconnected with my sister. Since then, we have
texted each other regularly.
As an advocate, brother, and gene
carrier who has luckily hit 65 without apparent symptoms, I felt duty-bound to check up on my
younger sister. She is 63. Our mother Carol died of HD at age 68 in 2006.
On July 15 Donna, her husband Barry,
my nephew Greg, my wife Regina, and I had a three-hour dinner at a restaurant
in Painesville. Though it was, potentially, a very awkward reunion, we
reconnected in a most cordial manner.
We were family, and we knew we had
to reunite to offer mutual support and understanding in the fight against HD. I
thanked Donna, Barry, and Greg for forming a team in the annual Huntington’s Disease Society of America Hope Walk (HDSA) fundraiser.
I have their permission to write
this article.
Left to right,
Gene Veritas (aka Kenneth P. Serbin), Donna, Barry, Greg, and Regina. Barry is wearing an HDSA Team Hope t-shirt (personal photo).
A
family reunion – and wonderful news!
We all caught up on one another’s
lives.
I squeezed Donna’s hand firmly
several times and looked into her eyes. Because of HD, she had to retire from
her job, and recently she stopped driving.
Barry, always the dedicated husband
and now a caregiver, detailed the adaptations he had made in their ranch house
because of Donna’s involuntary movements and instability in walking. She had five falls in their previous, two-story home.
As I had remembered him as a child
and young adult, Greg was ebullient, enthusiastically speaking of his work as a
computer programmer, his car, and his fiancé. He does not have HD symptoms.
We also discussed potential HD
disease-modifying treatments – slowing, halting, or reversing the progression
of symptoms.
I especially had in mind uniQure’s AMT-130, about which I had seen a presentation at the 20th Annual HD
Therapeutics Conference in February in February. The uniQure program seemed the closest to
seeking approval for its drug from the U.S. Food and Drug and Administration
(FDA).
Since our dinner, we have stayed in
touch.
On September 24, when uniQure
announced that AMT-130 had successfully slowed the progression of HD, I texted Donna and Greg with the news.
“Wonderful news!” Donna and Greg
both responded, echoing the elation of HD scientists and HD families.
I hope that we can continue to
rebuild our lost family ties and support one another in the fight against HD,
as we once did at the start of our HD journey with my mother’s diagnosis in
1995.
Rescuing
neurons from death
HD occurs because of the massive
death of brain cells (neurons).
AMT-130 is the first successful
disease-modifying HD drug. In the uniQure clinical trial, it achieved its main
goal and demonstrated a 75 percent slowing in the progression of the disease
over a three-year period.
On September 25, Ed Wild, M.D.,Ph.D.,
a professor of neurology at University College London and an investigator on
the uniQure program and senior advisor to the company, gave a podcast interview
to HD gene carrier Lauren Holder of Help4HD International.
Dr. Wild pointed out that “AMT”
refers to uniQure’s original name: Amsterdam Molecular Therapeutics. The Dutch
and American company was founded in 1998.
Because it is a gene therapy,
AMT-130 remains in the body permanently, thus allowing for the running of long
clinical trials and without the drawback of a possible placebo effect, Dr. Wild
explained. The effect of the drug “appears to be growing” over time, he added.
The 75-percent improvement went
“dramatically beyond what any one of us could have dreamed of,” he said, adding
that cognitive decline also slowed substantially.
AMT-130’s effectiveness lies in its
reduction of the abnormal huntingtin protein in the brain.
Dr. Wild observed that the slowing
of the disease has resulted from AMT-130’s “rescuing neurons” from death.
Because AMT-130 mainly targets the
striatum (deep in the brain), other areas such as the cortex might still need
treatment, perhaps done with another type of drug in a combination therapy, Dr.
Wild observed.
He added that additional studies of
the drug might be needed. “We’re up for all of that,” he said. “It’s putting
flesh on the bones of what is already a winning recipe.”
Important
details to be resolved
Many important details must be
resolved before AMT-130 reaches HD patients.
In early 2026, uniQure plans to
apply to the FDA for drug approval. Pending approval, the drug would be
launched in the U.S. later in 2026. uniQure would need to gear up its AMT-130
operations to coordinate with HDSA and other patient and clinical organizations
to inform the HD community about the drug and its availability.
Administering AMT-130 is far more
complex than the pills or spinal injections used in other clinical trial
programs: it involves 12 to 18 hours of brain surgery.
Dr. Wild noted that the treatment
will be “expensive.” “The drug is made from a virus and so it has to be
manufactured in specialized facilities,” he explained.
Dr. Wild estimated that, based on
previous gene therapies, AMT-130 will cost $2 million per person.
“It’s obviously a lot of money, but
we’re already spending a lot of money to keep people with Huntington’s cared
for, to manage the symptoms, to provide assistance to their families,” he
noted. The insurance industry, he said, also will need to agree to pay for the
treatment.
Waiting
for news of who can be treated
While the AMT-130 clinical trial
included people in stages 2 and 3 of the disease (stage 4 being the worst),
“it’s difficult to predict” who would get the treatment of an approved drug,
Dr. Wild explained. He said the community needs to have the FDA permit as broad
a label as possible: simply “Huntington’s disease.”
That label would allow people (like
Greg and me) who have tested positive for the HD gene but lack visible symptoms
to obtain the treatment. HD research has determined the disease process begins
at birth, with the damage building over life, Dr. Wild observed. Gene therapy,
a one-and-done treatment, is most potent when done early in life, he added.
Because of the conditions of accelerated approval granted by the FDA, uniQure would need to continue monitoring the drug, Dr.
Wild said. If the drug does not work, approval can be removed.
A
critique of AMT-130 and a call for accurate communication
Not everyone shares the same
enthusiasm for AMT-130. Ignacio Muñoz-Sanjuán, Ph.D., the CEO of Rumi Scientific, a drug discovery company focused on genetic and
neurological diseases, published a critique of uniQure’s AMT-130 data (click here to read more).
A native of Spain, Dr. Muñoz
co-founded Factor-H, a charitable organization seeking to assist poor HD
families in Latin America and raise awareness about their plight. He is the former vice president of translational biology
for CHDI Foundation, Inc., the largest
private funder of HD research and the sponsor of the annual HD Therapeutics
Conference.
Dr. Muñoz agrees that the AMT-130
results are “a turning point for the field of HD and, more broadly, for the
treatment of neurodegenerative conditions at large.”
However, Dr. Muñoz raised caveats
about AMT-130. He wrote, for instance, that the study “only showed the results
derived from 12 patients who have completed the full 36-month period” of the
trial and they were “in the early stages” of the disease.
Dr. Muñoz urged uniQure to analyze
data from “all individuals in the study.” With the “small number of individuals
receiving the therapy, one or two people could be disproportionately
contributing to the signals of protection demonstrated for the group average.”
Twenty-nine volunteers took part.
“Families deserve a realistic sense
of the commercial path ahead,” Dr. Muñoz added, advising “careful
communication” with HD families. Access will “dominate the conversation,” he
added, noting that “costs, geography, and the need for specialized neurosurgical
centers will slow availability, creating disparities that will frustrate many
families worldwide. The path to broad applicability will be slow and
difficult.”
‘Day
one of a new world’
I wish my parents, Paul and Carol
Serbin, were still alive to witness this moment in the HD journey! An “HD warrior,” my father was my mother’s HD caregiver for over ten years.
Paul and Carol
Serbin (family photo)
Although it is unclear whether
Donna, Greg, and I will even have access to AMT-130, the news of its efficacy
still brings us immense hope.
As my blog has documented the past
20-plus years, HD families face enormous stigma and tensions. I am overjoyed at
my family’s rapprochement at this promising moment.
As Dr. Wild noted, before AMT-130
more than HD 100 clinical trials had been run, without disease modification.
“It’s day one of a new world, but
it’s up to us to define the characteristics of that world and make sure that
it’s capable of delivering the benefit to everyone who needs it,” including, he
said, poor HD families in Venezuela who contributed blood samples in the search
for the huntingtin gene.
“No one is free until everyone is free,” he
said.
