Solving Schizophrenia

For Schizophrenia Awareness Week (starting 17th May) we caught up with Professor Huang to find out if he was any closer to finding the cause of and a cure for schizophrenia. He also shares interesting discussions he's had with colleagues around COVID-19 symptoms in schizophrenia patients.

“In terms of the cause of schizophrenia, we know a lot more now than we did five years ago. Our group at UOW has contributed to this advancement but we are very much part of a large collaborative effort. So five years ago we thought it's the genetics, it's a gene that plays a big role in having schizophrenia. We’ve since found that the environment also plays a big role particularly in early brain development. Now on top of that, we know more in terms of the immunology and the areas of the brain affected. And gradually we are down to two critical areas: the neural connectivity and immunology.
That is what we really want to focus on to understand what it is in the brain that causes schizophrenia.”  

Professor Huang has important connections in Chinese research institutes and hospitals and other research groups in the US and Indonesia. He believes that the challenge of understanding the cause of schizophrenia cannot be achieved in one group or even by one country – it must be an international effort. 

“I'll give you one example. We have just published a new publication (in the journal Frontiers in Psychiatry) about a new way to treat schizophrenia in terms of linking to the pathology, focusing on the neural connectivity specifically. The trial conducted in China involved 200 schizophrenia patients.”

“The trial involved applying a new method to the patients: rTMS which stands for repetitive transcranial magnetic stimulation. Basically you'll use a stimulation to generate a small magnetic environment in the brain. We'll give that to the patients. This method has been used to previously treat Parkinson's disease and we now use this method to improve neural connectivity. The results are really great, very significant improvement in terms of cognitive function.”

“The downside of the rTMS is low resolution in precision. Along the same line of a non-pharmacotherapy approach, we are working with another research group at UOW led by Professor Gordon Wallace. The collaborative project with the ARC Centre of Excellence for Electromaterials Science (ACES) has shown that the use of electrical stimulation can improve connectivity and now we are developing a device for a wireless electrical system. While it is at the early stage of development, it has generated some promising results.”

The research involves Professor Xiangyang Zhang at the University of Texas Health Science Center and Department of Psychiatry and Behavioural Sciences (USA) for the clinical study, Professor Robert Foster at Dublin City University in Ireland who using an emerging technology ‘bipolar electrochemistry’, and in a parallel project, Associate Professor Mario Romero-Ortega at the University of Texas, Austin USA who is working on wireless stimulation systems using graphene fibre sutrodes. 

Another line of investigation by Prof. Huang’s team is improving drug treatments. Currently drugs used to treat schizophrenia can induce side effects such as obesity and cardiovascular disease, which significantly reduces the lifespan of patients. The team is looking at developing a new line of drugs and Prof. Huang is particularly excited about 2 candidate drugs that could be used in human clinical trials soon. 

“It is actually the main focus of the neuropharmacology work of our group. There are three lines of research: modifying current drugs, developing new drugs and initiating molecular nutrition for the brain.

“Firstly, we're going to modify an old drug by changing specific sites of the compound, by using computer modelling, drug binding affinity assay, in vitro and in vivo studies.  In the beginning we had over 10 candidate compounds. After careful screening, we now have 2 good candidate drugs. They have very much passed most of our preclinical trials. Now it needs to do the very last thing called pharmacokinetic and pharmacodynamic study. We will make sure there's no toxicity prior to any human clinical trials.”

The modified drug compound line of research is close to completion, and could see a clinical trial in 3- or 4-years’ time but the new drug compound research, of which they have 3 types they are currently investigating, will take significantly longer before any trials can begin.

Prof. Huang describes drug development as very complex and involving many critical steps such as safety and therapeutic efficacy.

“One drug can take 10 years of development and testing before it can be used to treat patients. However molecular nutrition has no toxic effects and can be administered to patients immediately, with the aim of enabling the cells to grow and expand their connectivity in a particular area of the brain.” 

His research team is at an early stage of screening a number of nutritional molecules. 

Now, with the outbreak of COVID-19 Prof. Huang is looking to initiate a research project which may help with finding a drug target for the disease. He is collaborating with a psychiatric hospital in China where the comparison could be made of COVID-19 infection severity between schizophrenia patients and other vulnerable populations, especially the elderly.

“Schizophrenia patients have a very different immune system and can quite often go through life without developing cancer or even the common cold for example. If we look at the antibodies they develop once infected with COVID-19 and compare that to another COVID-19 patient group it could reveal some very important information for the drug that needs to be developed.”

“Scientists know a lot of the biology of Covid-19 now and that's great, but it's very important that we know what type of people are more vulnerable to infection while others are resistant. We need to know what is different with their immune system.”  

However, his main focus remains clear – to find the cause of schizophrenia and a cure. When asked how much longer he’ll be leading his team in this research area, Prof. Huang says he is not quite ready to finish up. 

“I think I should find a better cure. I suppose as long as that takes. I've been working for so long in this research area, the whole program set up took nearly 20 years to get to this level. But I feel we have some light at the other side of the tunnel. I really think we will get patients to benefit from our research. When you come to the hospital, you see these patients, they do not deserve to suffer for the rest of their lives. We need some cure and we need this cure urgently. Anything that can help them, to whatever degree, if not a complete cure. That is a help and that's what they need. That's why we should keep working on it and never give up. I will continue to work in this area particularly now we have the support of the NHMRC and our international collaboration. I hope in the next four to five years we really can produce something to help those patients.”

* Data is from Scopus and Google Scholar. Numbers are based on Articles, reviews, conference papers, books and book chapters.