Researchers have
shown that it could be possible to modify the mitochondrial genome, paving the
way for new treatments for incurable mitochondrial diseases.
Researchers from the University of Cambridge, UK
have shown it is possible to repair defective mitochondria using gene-editing
techniques in live mice. The breakthrough, which was recently published in
Nature Communications, is a step toward new treatments for incurable
mitochondrial diseases.
Faults in mitochondrial DNA can affect how well the
mitochondria operate, leading to mitochondrial diseases, serious and often
fatal conditions that affect around one in 5,000 people. Usually, more than 60
percent of the mitochondria in a cell need to be faulty for the disease to
emerge and the more defective mitochondria a person has, the more severe their
disease will be. If the percentage of defective DNA could be reduced, the
disease could potentially be treated. A cell that contains a mixture of healthy
and faulty mitochondrial DNA is described as ‘heteroplasmic’. If a cell
contains no healthy mitochondrial DNA, it is ‘homoplasmic’.
In 2018, a team from the MRC Mitochondrial Biology
Unit at the University of Cambridge used an experimental gene therapy treatment
in mice and were able to successfully target and eliminate the damaged
mitochondria DNA in heteroplasmic cells, allowing mitochondria with healthy DNA
to take their place. Although this research was promising, the technique would
only work in cells with enough healthy mitochondrial DNA to copy themselves and
replace the faulty ones that had been removed. Furthermore, it would not work
in cells whose entire mitochondria had faulty DNA. In their latest research, the team used a
biological tool known as a mitochondrial base editor to edit the mitochondrial
DNA of live mice. The treatment was delivered into the bloodstream of the mouse
using a modified virus, which was then taken up by its cells. The tool looked
for a unique sequence of base pairs: combinations of the A, C, G and T
molecules that make up DNA. It then changed the DNA base (in this case,
changing a C to a T), highlighting the tool could correct certain combinations
that cause the mitochondria to malfunction.
There are currently no suitable mouse models of
mitochondrial DNA diseases, so the researchers used healthy mice to test the
mitochondrial base editors. However, the research shows that it is possible to
edit mitochondrial DNA genes in a live animal.
“There is clearly a long way to go before our work
could lead to a treatment for mitochondrial diseases. However, it shows that
there is the potential for a future treatment that removes the complexity of
mitochondrial replacement therapy and would allow for defective mitochondria to
be repaired in children and adults,” concluded Dr Michal Minczuk, an author of
the study.
World Journal of Case Reports and Clinical Images (ISSN 2835-1568)
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