Page 24 - ScienceFocus_issue11_flipbook

Genetic diseases, caused by abnormalities in a

person? genome, are typically extremely difficult to treat, and many
are incurable. Spinocerebellar ataxia (SCA) is one of them. It is a
degenerative disease that eventually strips patients of their ability
to coordinate movement. There are numerous types of SCA, with
each type affecting a different gene and manifesting into a specific
set of symptoms. Physiotherapy is often prescribed but only relieves
symptoms to a certain degree. SCA40 was discovered by Prof. Edwin
Ho-yin Chan during a three-year study of the genetic sequence of SCA
patients in Hong Kong. He is Professor of Life Sciences at The Chinese
University of Hong Kong and Director of the Laboratory of Drosophila
Research.

In the latter part of the 90s, it was nigh impossible to identify genes
that caused genetic diseases. The gene mutation responsible for
causing cystic fibrosis, for instance, was not discovered until 1988 by
Francis Collins, Lap-Chee Tsui and John R. Riordan. As a high school
student and college freshman, Prof. Chan aspired to follow in their
footsteps. In his junior year in college, Prof. Chan met his mentor, Dr.
Sandy Luk, who urged him to first understand the biology of normal
individuals before investigating pathological conditions. Equipped
with his mentor? sage advice, he began studying developmental
biology on the fruit fly, Drosophila melanogaster and conducting
research which helped explain how genes control
an organism? egg development, as many genetic
diseases unfold from young. Thus began his
commitment to biomedical research.

Prof. Chan? life? work began in 20 02 after
he had returned to Hong Kong from University
of Pennsylvania, bringing with him the dream
to dedicate himself to the SCA patient society.
Together with the Hong Kong Spinocerebellar Ataxia
Association, scientists, neurologists and genetic
counsellors, they created a spinocerebellar ataxia
patient registry that compiled patient data. It was
during this period that they came across the SCA40
family ??where five individuals were diagnosed with
adult-onset spinocerebellar ataxia. Using genetic
and biochemical analyses, Prof. Chan and his team
were able to isolate the mutation in a gene called
CCDC88C in these patients. Carriers of this gene
mutation will develop SCA40.

Identification of the mutation is pivotal to
developing better treatment and a potential cure
to SCA40. ?e take a structure-based drug design
approach to develop inhibitors that can neutralise
RNA-toxicity in SCAs. Based on the toxic RNA
structure, we virtually fit molecules to the RNA and
attempt to find one that binds tightly to the toxic RNA,??said Prof. Chan, ?fter we identify such molecule(s),
we then synthesise these compounds in the lab and then test them in our disease models, including iPSC,
Drosophila and mice??

Parallel to the research on SCA40, Prof. Chan and his team also investigate other neuromuscular
diseases, including myotonic dystrophy and amyotrophic lateral sclerosis (ALS). The latter garnered viral
attention in 2014 in an activity called ?he ALS Ice Bucket Challenge?? aiming to bring awareness and
donation toward ALS research.