March Celebrating the Sucess of Dr Isma Liza Mohd Isa for IWD

While still a PhD candidate, Dr Isma Liza Mohd Isa invented a therapeutic biomaterial as an interventional strategy for low back pain treatment in degenerative disc disease. Recently awarded a research grant from the Health Research Board, Ireland, under the Emerging Investigator Award for Health 2022, Isma will now be working to develop disc-on-a-chip for the modelling of patient-specific disease development of intervertebral disc degeneration and underlying inflammatory pain. She sat down with us recently to talk about her career to date, and the potential impact her work will have on patients in future.

What inspired you to become a researcher? Do you have any specific memories that set off a spark?

My enthusiasm for medical science and love to explore new things. It started during my PhD study in CÚRAM and Anatomy, at the University of Galway, Ireland. With the success of my PhD research, I was most inspired to pursue my career as a researcher and lecturer in academia. I invented a therapeutic biomaterial as an interventional strategy for low back pain treatment in degenerative disc disease, which was my major achievement during my PhD study. This was a huge motivation for me to keep going contributing to research. I am involved in research to develop new treatment strategies through the current advancement of medical technology for chronic diseases. I believe bench to bedside, which is translating science from the lab to the clinic, could save people's lives or at least improve the lives of patients.

Can you tell us about the research you’re currently working on? 

I am expanding my research field in the intervertebral disc from my PhD. My research focuses on intervertebral disc degeneration (damage), specifically employing therapeutic biomaterials and stem cells for tissue repair targeting low back pain and disease modelling. The intervertebral disc is a pad of cartilage between our backbones. I am developing a biomaterial in a hydrogel format to mimic the nucleus pulposus (NP), a jelly-like core region in the intervertebral disc. The hydrogel technology is designed as an injection system or medical device implant for minimally invasive procedures or surgical implantation for the spine application. I collaborate with Prof Datuk Dr Sabarul Afian Mokhtar, a senior spine consultant at Orthopaedics and Traumatology UKM to gain clinical input in the project.

Under the young researcher grant UKM, I lead a project on hydrogel’s biocompatibility and immuno-modulatory effect in the organ culture model. I collaborate with Bioserasi Lab, UKM, for the safety testing of hydrogel formulation in accordance with the ISO standard of medical devices, Dr Fairus Ahmad in Anatomy UKM and Dr Sibylle Grad of AO Research Institute, Davos, Switzerland to grow the intervertebral disc organ in the lab for hydrogel testing.

In collaboration with Assoc Prof Dr Mohd Fauzi Busra from the Centre for Tissue Engineering and Regenerative Medicine (CTERM) UKM, we also grow stem cells in the lab. We incorporated them within the 3D hydrogel system to guide them to become disc-like cells before implanting them within the hydrogel in a pre-clinical pain model in intervertebral disc injury. We aim to see the efficacy of this technology in promoting tissue healing and relieving pain in the intervertebral disc. I am the principal investigator in this project received funding from the Malaysian Ministry of Higher Education under the fundamental research scheme, which is a collaborative project between the Department of Anatomy, CTERM, the Department of Orthopaedics and Traumatology UKM as well as Pharmacology and Therapeutics, School of Medicine, University of Galway, Ireland.

My current research has evolved from developing hydrogel technology with stem cells for regenerative therapy towards precision medicine for disease modelling in intervertebral discs. I recently secured a research grant from the Health Research Board, Ireland, under the Emerging Investigator Award for Health 2022 to develop disc-on-a-chip for the modelling of patient-specific pathogenesis of intervertebral disc degeneration underlying inflammatory pain. In this project, I will employ a precision medicine approach to prospectively study transcriptomic profiling of neuroinflammation markers in degenerative disc disease patients at multi-centre. The information from this study will lead to the developing a disc-on-a-chip model using 3D (bio)printing for disease modelling and pharmacological modulation. This is a multidisciplinary project in CÚRAM under the mentorship of Prof Abhay Pandit, the director of CÚRAM and co-mentor Prof David P Finn in Pharmacology and Therapeutics, University of Galway, involving cross-country research collaboration with Prof Aiden Devitt (Orthopaedic Surgery Galway University Hospital), Dr Patrick Kelly (Paediatrics Orthopaedic Surgery, Children Health Ireland Crumlin Dublin), Prof Datuk Dr Sabarul Afian Mokhtar (Orthopaedics and Traumatology UKM, Malaysia), Assoc Prof Dr Elvy Suhana Mohd Ramli (Anatomy UKM, Malaysia), and Prof Sulayman Dib-Hajj (Center for Neuroscience & Regeneration Research, Yale School of Medicine, USA).

Tell us why is your research important?

Lower back pain is an unmet medical need; estimating that 42% of those who experience lower back pain are associated with degenerative disc disease. It is a leading cause of disability worldwide, causing a huge socio-economic burden to the country. Current treatments include medication, rehabilitation and surgical interventions that aim to reduce pain. Nevertheless, none of the treatments could restore intervertebral disc anatomy and functions. My goal is to find better solutions to relieve pain in patients and promote disc repair anatomically while maintaining mechanical functions without removing damaged discs.

My research is also advanced towards the current trend of research. I employ a precision medicine approach in developing patient-specific disease models. Transcriptomic profiling in the subgroup of degenerative disc disease patients will explain the mechanism and key markers underlying painful disc degeneration at defined disease severity. The disc-on-a-chip model will provide a disease platform to investigate the patient-specific pathogenesis of painful disc degeneration, allowing for rapid prototyping through a 3D (bio)printing method and a high-precision drug testing system before clinical trials.

What commercial applications do you foresee for your research?  

The hydrogel could be designed in an injectable format as an early intervention via minimally invasive injection. The hydrogel could also be designed as an advanced cell delivery system for stem cells via minimally invasive injection or surgical implantation at an advanced stage of the disease. Both strategies aim for tissue healing and relieving pain.

The disc-on-a-chip could be a platform for in vitro diagnostic medical devices (IVDR)in testing new drugs for painful intervertebral disc degeneration.

What are some of the biggest challenges you face as a researcher in your field?

We might see positive findings in the lab-based studies. A concern might be that we cannot see similar findings in humans. Only clinical trials could determine the efficacy and safety of the technology. Therefore, we must perform extensive lab-based studies, before testing it in humans.

The disc-on-a-chip is a disease prototype that may not 100% replicate the pathologic features of painful disc degeneration.

What are some of the areas of research you’d like to see tackled in the years ahead?

I would like to design the technology (treatment) tailored to the severity of the disease in the sub-group of patients, which could help prevent disease progression and enhance the efficacy of the treatment without complications. The technology could be minimally invasive and cost-effective.

Dr Isma Liza Mohd Isa is an emerging Principal Investigator at CURAM, Honorary Senior Lecturer in Pharmacology, in the School of Medicine at the University of Galway and Senior Lecturer in the Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan in Malaysia.