Novartis is offering US insurers pay-as-you-go plans,
as well as refunds if the treatments stop working.
But while medical miracles are taking place
because of gene therapy, that hasn’t been the case
for the Donnell children. In part because they are too
old; Abeona trials show that children are most likely
to benefit from gene therapy if it is administered in
infancy. Once brain damage has begun, it’s difficult to
reverse.
Furthermore, in order to qualify for gene therapy
trials, children have to be free of antibodies to the
viruses that act as ferries for the gene – and one of the
Donnell children did carry antibodies.
When I caught up with Megan in September
2019, nine-year-old Isla was back to nappies and
Megan was sporting a black eye from her frustrated
daughter. But she was far, far from beaten. The
Sanfilippo Children’s Foundation is moving ahead
on multiple fronts. And once again, I was stunned by
what she had to tell me. She was funding a research
scientist who was making organoids of her children’s
brains in order to test drugs that could slow the
progress of their disease.BRAIN ORGANOIDS proved their value during the
2015 Zika virus outbreak in Brazil. Babies were
being born with abnormally small heads, a condition
known as microcephaly. But there was debate as to
whether the virus was responsible. Researchers used
human brain organoids to show that
the virus infected and delayed the
development of certain types of brain
cells.
Megan was now commandeering
this technology to make braintreatment for children born with spinal muscular
atrophy (SMA). Until a couple of years ago, there
was no hope for babies born with this condition; they
became paralysed and died by the age of two. But
babies treated with the gene therapy Zolgensma,
marketed by Novartis, have reached the age of four- with many of them walking and some dancing. At
a cost of more than US$2 million per treatment, it is
the most expensive drug in history.
Spectacular results have also been seen for
children suffering from a form of retinal blindness
that begins months after birth. A gene therapy called
Luxturna, marketed by Roche at a cost of US$850,000
per patient, has restored sight to blind children.
With the lame walking and the blind seeing,
paediatrician researcher Ian Alexander at Children’s
Medical Research Institute in Westmead, Sydney,
has dubbed these “biblical results”. And for the first
time that I can recall, medical researchers are using a
four-letter word:cure.
Governments and health insurers around the
world are now confronted with the dilemma of
how to pay these exorbitant prices. Gene therapy
advocates argue that one-shot cures end up saving
money because most genetic diseases incur costs of
tens of millions of dollars through ongoing treatment
and hospitalisation. But that calculation depends on
whether or not single shot cures such as Zolgensma
do indeed last a lifetime, which remains to be seen.
The remarkable ability to make a facsimile of a
person’s brain to study their disease relies on the
braiding together of two streams of epic research.Brain organoids are artificially
grown organs which can mimic
brain structure (opposite).
To make an organoid, start
with a patient’s skin cells and
transform them into induced
pluripotent stem cells. Culture
them in a brew that includes
pattern-forming genes to
induce them to become
progenitors of brain tissue –
neuroectoderm. Then grow
them in a gel droplet and
rotate them in a bioreactor.
Human pluripotent stem cellsSpin cerebral organoids in bioreactorInduce neuroectodermGrow in gel droplet Cerebral organoid readyCultivate embryoid bodiesKEVAL TILVA80 – COSMOS Issue 86BRAIN ORGANOID