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20 September 2024 | Story André Damons | Photo Supplied
zebrafish-blue-in-aquarium
Zebrafish blue in an aquarium.

A researcher from the University of the Free State (UFS) hopes to make living with epilepsy and other diseases of the central nervous system (CNS) easier by using South African plants extracts which may have anti-epileptic properties and testing them on zebrafish larvae.

Prof Anke Wilhelm, Associate Professor and Divisional Head of Organic Chemistry in the UFS Department of Chemistry, focuses her research on the isolation of active GABAergic compounds (substances that affect the brain’s GABA system, which helps control nervous system activity) by using a test that measures the movement of zebrafish larvae.

Even though obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process, Prof Wilhelm hopes to contribute to the better pain management of people suffering from epilepsy and diseases of the CNS through an affordable alternative drug with less side effects.

The tests are done in a zebrafish bioassay (an analytical method to determine the potency of a substance by its effect on living animals) housed at the UFS’ Chemistry Department.

Why zebrafish larvae?

Prof Wilhelm, who is a National Research Foundation Y2-rated synthetic organic chemist, says zebrafish share about 70% of their genes with humans, and about 84% of human genes known to be associated with diseases have a counterpart in zebrafish. This makes them a valuable model for studying human biology and disease.

“Zebrafish are powerful tools for modelling a wide range of CNS diseases, contributing significantly to the understanding of disease mechanisms and the development of potential treatments,” she says. “Mood disorders, anxiety, insomnia, and attention deficit hyperactivity disorder (ADHD) are all diseases which may be studied through this bioassay.”

She explains that the zebrafish larvae are studied seven days after fertilisation in their bioassay. The larvae are incubated with the specific plant extract at a certain (non-toxic) concentration for three hours. Pentylenetetrazol (PTZ), a GABAA receptor antagonist that has been extensively used in rodent models for acute seizure and anxiety, is then administered to induce concentration-dependent seizures in the zebrafish larvae.

“GABA receptor antagonists are drugs that inhibit the action of gamma-aminobutyric acid, the chief inhibitory neurotransmitter in the mammalian central nervous system,” Prof Wilhelm says. “A specialised infrared camera is then used to track the movement of the larvae inside a chamber. The data is then converted into a graph which shows the movement of each larva over 30 minutes.

“If lowering of movement is observed at a specific concentration it means that the plant extract may have the potential to be used as an epileptic drug, since it has the ability to counteract the induced seizure in the larvae. This bioassay is extremely useful in drug discovery and toxicity screening of plant extracts.”

Zebrafish embryos, she says, develop quickly, with major organs forming within 36 hours of fertilisation. This rapid development allows researchers to observe the effects of experiments in a short period. The maintenance of a zebrafish model is less costly and labour-intensive than using a rodent model. “The use of zebrafish larvae allows for high-throughput screening due to their small size and transparency, which facilitates observation of CNS-related effects. Their genetic and physiological similarities to humans make them a valuable model for early-stage drug discovery.”

Potential uses

The next step in the research, according to Prof Wilhelm, is to identify a single compound from a natural source which may have potential anti-epileptic activity while causing less side effects than current drugs on the market. Researchers would then investigate the possibility of synthesising such a compound on a large scale, to eliminate the use of a natural resource and promote sustainability.

“Many plant extracts which I have screened show a synergistic effect in the zebrafish bioassay, meaning that the extract or the combination of compounds shows potential, but the isolated compounds are inactive. Even if a plant extract shows promise in preclinical and early clinical studies, obtaining regulatory approval for use as a treatment for epilepsy is a long and complex process.

“This includes demonstrating consistent efficacy, safety, and quality in large-scale clinical trials. One of the major challenges in using plant extracts is the lack of standardisation. The concentration of active compounds in plant extracts can vary depending on factors like the plant's growing conditions, harvest time, and extraction methods. This variability makes it difficult to ensure consistent efficacy and safety, therefore this is a time-consuming process.”

Green chemistry

After being approached by Dr Glen Taylor, Senior Director of the UFS Directorate Research Development (DRD), in 2017, regarding funding for Noldus Daniovision equipment, Prof Wilhelm received training from Prof Matthias Hamburger of the University of Basel in Switzerland on how to use such equipment. The larval zebrafish locomotive bioassay was established at the UFS Chemistry Department during 2017 and 2018 and now provides a third-stream income for the department, in conjunction with the Department of Genetics, where the adult zebrafish are housed.

Prof Wilhelm’s other research interests include green chemistry, food sustainability, and recycling. She is looking into green extraction techniques using non-conventional extraction methods to recover valuable bioactive compounds from agricultural and food residues. “Techniques like ultrasound, microwave-assisted extraction, and the use of deep eutectic solvents are becoming popular for their efficiency and alignment with circular economy principles.”

News Archive

Juan Odendaal on his way to World Champs
2015-03-23

Juan Odendaal
Photo: BOOGS Photography, Andrew McFadden

UFS’s athletes with disabilities are currently excelling in cycling and athletics.

The UFS Para-cyclist, Juan Odendaal, will soon make his debut for South Africa at the 2015 Union Cyclist International (UCI) Para-cycling Track World Championships in Apeldoorn, The Netherlands, from 26-29 March 2015.

The Championship event will provide an excellent foundation for re-building the international competitiveness of South Africa’s Para-cycling track team in the build-up to Rio 2016. In a situation where the UCI has hosted relatively few international track competitions over the past three years, the 2015 World Championships will serve as a stepping-stone to the 2016 grand season, when it is expected that the country’s top riders will reach their peak competitive condition.

As the youngest member of the South African team, Odendaal will use the opportunity of competing in the individual time trial and team sprint events to build a platform for an international career will certainly span many years to come.

Another UFS student, Musa Simelane, are excelling and was chosen for the SA Wheelchair Rugby tean, known as the "Wheelboks". They will compete in the 2015 World Wheelchair Rugby Challenge in London in October and after that head to Japan to compete in the 2015 Asia Oceania Championships.

On a local level, earlier in March this year, other UFS athletes with disabilities also performed well on the athletics track.

Blind athlete and member of the Bloemfontein Campus Student Representative Council (SRC), Louzanne Coetzee, also had a good 1500m race in the beginning of March when she qualified easily for the World Championships, which will take place in Toronto, Canada, later this year. Coetzee and her guide, Rouxné Jacobs, set up a time of 5:45.86, which is well under the required standard of 6 minutes.

The other blind UFS athlete, Danie Breitenbach, alongside his guide Marius Wessels, broke his own national record for the 800m again on Friday 6 March 2015. In November 2014, Breitenbach’s record stood at 2:15.17. This record now stands at 2:13.57. Chances now are that Breitenbach will reach his goal of running the 800m under 2:10 at the Nedbank National Championship for the Physically Disabled at the end of March 2015.

The other Kovsie stars who will be participating at the Nedbank National Championship for the Physically Disabled are as follows:

Athletes:
• Dineo Mokhosoa
• Louzanne Coetzee
• Danie Breitenbach
• Juanré Jenkinson
• Diederich Kleynhans
• Jacques de Bruyn

Swimmer:
• Johann van Heerden

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