Genetic
disorders are
abnormalities that exist at birth or from
new mutations in the genome. Until recent
decades, genetic disorders were not well
understood, but gene therapy, which aims
to restore the normal sequence of DNA
after a mutation, has helped significantly. Prof.
Adrian Bird, 2016 Shaw Laureate in Life Science
and Medicine, shared the Shaw Prize with Prof.
Huda Y. Zoghbi, in making substantial advances
in treating a particular genetic disorder known as
Rett syndrome, which affects the grey matter in
the brain. They discovered the encoded proteins
that recognise a chemical modification of the DNA
which influences gene control as the basis of the
developmental disorder.
Rett syndrome is brought about by mutations in
the gene MeCP2 on the X chromosome and can
cause developmental problems in babies such
as small hands and feet as well as microcephaly
in some cases (slowed rate of head growth). Prof.
Bird found that mice with MeCP2 mutations also
displayed similar clinical features of Rett syndrome.
In both humans and mice, the syndrome causes
neurons to be smaller and less active. Prof. Bird
attempted to correct the mutation by replacing
the missing MeCP2 protein in mice, yielding positive
results after gene restoration. The experiment
establ ished that Ret t syndrome is, at least in
principle, a treatable condition.
This elegant solution has been predicted to be
adapted for human treatment in the near future.
Prof. Bird and his collaboration with scientists from
the U. S. have recently attempted to engineer
gene therapy in mice. The MeCP2 gene would be
delivered using a virus as a vector, an approach
that would in theory be adaptable to humans.
Mice treated with this therapy showed marked
improvement in symptoms. However, there is still
a long way to go before their experiment can be
applied to human clinical trials.
Wh i le ground-break i ng and undoubtedl y
exciting, gene therapy has historically encountered
numerous setbacks. Prof. Bird said:
Perseverance, imaginative and
patience are some of the prerequisites
for being a scientist.
He discovered the MeCP2 protein back in
1992 but many of its functions are still shrouded in
mystery to be unraveled. He believes that the best
way of conducting research is to test hypotheses
rather than to continuously collect biological data
as a means to gain real knowledge. Thus, he insists
on bold experiments and is not afraid of destroying
hypotheses that he holds dear.
My dream is that I am still
doing science when this distressing
disorder is finally cured.
Prof. Bird’s laborator y remains interested in
genome organization and, in particular, in how
epigenetic markers are laid down to assist and
manage gene activity. Part of his group works on
CpG islands and DNA methylation. Their research
on Rett syndrome is ongoing and they have plans
to test new hypotheses about MeCP2 and its
correlation to Rett syndrome. The ultimate goal is
aimed at making Rett syndrome gene therapy a
reality.
with
Structure of the
MeCP2 protein
(Image credits:
Emw)
Gene
Therapy
2016 Shaw Laureate in
Life Science and Medicine
2016年度邵逸夫生命科學與醫學獎得主
