CUHK Passions and Pursuits

3 P rof. Edwin Chan is a champion for sufferers of spinocerebellar ataxia (SCA). He has identified a specific gene that causes one version of the disease. And he and a partner in Denmark are working on drugs to prevent the onset of the disease altogether. SCA patients have fully clear and functioning minds, but often have blurred speech and vision. They cannot walk freely due to tremors, because their cerebellum, the part of the brain that governs motor control, is not functioning normally. They demonstrate many of the same symptoms as people with motor- neuron disease. But SCA kills cells in the brain, while motor-neuron disease targets cells in the limbs. It normally takes a MRI scan and a series of physical tests to diagnose SCA. SCA is just one of around 6,000 conditions in the world that are classified as ‘rare diseases’, defined in Europe as those that affect one in 2,000 people. They are so rare that Hong Kong—well behind the West in treating them—doesn’t even have a definition, and has no system in place for supporting patients. They are normally hereditary diseases—80% of them are genetic. They are frequently disabling, affecting the patient’s entire life, and occasionally degenerative and life-threatening. But there is often no treatment, or even ways to alleviate the symptoms. There are more than 40 subtypes of SCA. Professor Chan has concentrated on the polyglutamine subgroup of six SCAs, in which stress within the nucleolus, a small part of the nucleus, causes cell death in the neurons of the brain. The main agent in the process is nucleolin, a protein that causes stress in the brain if it malfunctions. Professor Chan tracked the process to its origin. He identified that nucleolin gets ‘hijacked’ by a certain form of toxic ribonucleic acid (RNA). The nucleolin does not function properly c c From left: Prof. Edwin Chan, Dr. Stephen Chen, SCA patients Mr. Cheng and Mr. Fung as a result, ultimately resulting in the death of the cell. Having identified the process, Professor Chan set about designing a drug to prevent the cell hijack from occurring in the first place. He set about a systematic screening of peptide sequences, and made an educated guess that one of a family of six peptides might work. The peptide acts as a decoy, getting sucked up and hijacked by the RNA instead. By introducing the peptides into animal cells, Professor Chan tested whether or not they halted the cell death. Two of them proved to be very promising. He then turned to a partner in Denmark, Knud Jensen , a professor of peptide engineering at the University of Copenhagen, to synthesize them. With Chan designing the peptide and Jensen manufacturing it, they are developing therapeutics that can block that nuclear pathway, and hold the potential for drugs. A Rare Talent for a Rare Disease Edwin Chan takes on Spinocerebella Ataxia