their parents, they acquire mitochondria only from
their mothers because the sperm mitochondria don’t
make it into the female egg during fertilisation. As
a result, the fertilised egg develops into an embryo
carrying only its original female mitochondria.
“A woman with mitochondrial disease can pass it
on to her offspring, but it’s not a sure thing,” Dr Marni
Falk, executive director of the mitochondrial medicine
frontier program at Children’s Hospital of Philadelphia,
told Global Health Asia-Pacific. “It depends on the
percentage of mitochondrial DNA with the mutation.”
This is because there are about 250,000
mitochondria in an egg cell, and each one of them
stores hundreds of mitochondrial DNA copies. If a
significant percentage of these copies are abnormally
mutated, say 80 percent, then women are likely to
have severe symptoms of mitochondrial disease and
to pass the condition on to their babies. However,
when the figure doesn’t exceed 10 percent, the
disease is unlikely to be passed on.
Some women with mitochondrial DNA mutations
may never know they have them because they’re
healthy and show no symptoms, but this doesn’t mean
their kids are protected from transmission. While
symptomatic women have up to a 50 percent chance
of conceiving a child with mitochondrial disease,
the likelihood is one in 25 for women without any
symptoms.
Although next-generation sequencing for genetic
testing can work out the mutation level a woman
carries, it’s still a matter of chance whether babies will
be affected.
“It’s like a jar of red and green jellybeans, with the
red being the mutated genes and the green being
the normal ones. If you put your hand in the jar, it’s
impossible to predict with certainty how many reds
you’ll pull out,” explained Dr Falk. “If there’s only one
red among thousands, it’s very unlikely you’ll get it,
but if there are 99 out of 100, you’re very likely to pull
them out.”
“They’re an important part of the human genome
and are potentially involved not only in mitochondrial
disease but also other conditions,” he said.
In addition, the energy-producing structures have
a special relationship with their corresponding nuclear
genes. “A very important part of mitochondrial DNA
regulation occurs at the hands of nuclear genes.
Therefore, it’s crucial to keep intact this interaction
between nuclear and mitochondrial genomes,” he
added.
One potential problem is that, if not all donated
mitochondria can provide a suitable match for the
mother’s nuclear genes, nuclear genome transfer
could then lead to unknown complications. “A
mismatch between nuclear and mitochondrial genes is
a potential source of risk. We just don’t know to what
degree,” said Dr Falk.
According to Dr Keefe, some animal experiments
suggest nuclear genome transfer could even lead
to neuropsychiatric symptoms, like depression, and
sterility.
Potential risks must be considered in light of the
availability of alternative ways to have an unaffected
child. “There’s no strictly medical justification [to
perform the procedure] as the main purpose is to have
genetically-related babies,” pointed out Darnovsky.
“Understandably, this is something important to
some people, but it’s not a medical issue, it’s a social
benefit. If you accept that understanding of the
technique, you’ll want a very high level of assurance
that you’re not putting babies at risk for future
problems.”
Efficacy, risks, and alternatives to nuclear
genome transfer
One way of viewing mitochondrial replacement
therapy (MRT), another more common name for the
controversial procedure, is to consider it as a slight
upgrade to improve the body’s efficiency.
This idea is often supported by the argument that
the donated mitochondria make up just a tiny bit of the
engineered embryo while their key function is simply
to provide energy for biological processes.
Supporters of MRT often downplay the significance
of the cellular changes, comparing them to replacing
the batteries in a camera, said Marcy Darnovsky,
executive director of the not-for-profit Centre for
Genetics and Society, noting that this was a big
oversimplification.
Dr Keefe agrees that characterising mitochondria
as simple power plants is widely incorrect because
they also play metabolic and immune functions.
GlobalHealthAndTravel.com
MARCH 2020
53