Changes in the immune system following AHSCT

dr-malini-visweswaran

Dr Malini Visweswaran

St Vincent's Centre of Applied Medical Research, NSW

| Better treatments | Immunology | Fellowship | 2021 | Investigator Led Research |
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Summary

There has been significant interest in the potential of autologous haematopoietic stem cell transplantation (AHSCT) to improve clinical outcomes for people living with MS. AHSCT has been shown in previous research, including studies conducted by scientists at St Vincent’s Hospital in Sydney, to “re-set” the immune system, possibly leading to disease remission and better outcomes for people living with MS. However, the type of individual most likely to benefit from AHSCT is still being determined.

St Vincent’s Hospital in Sydney is one of the leading hospitals performing AHSCT in MS in Australia and has a strategic partnership with MS Australia to advance cellular therapies such as AHSCT. St Vincent’s Hospital also has a biobank of blood samples collected from people living with MS over time, both before and after the AHSCT procedure.

Dr Visweswaran and her team hope to shed light on how AHSCT induces the beneficial effects seen in MS. Current thinking is that changes to the metabolic state of immune cells may be important in this process. This concept will be investigated in this study by closely examining the metabolic profile of immune cells to see how the transplant affects their metabolism.

The research team has access to the biobank of blood samples and clinical progress reports of past patients and can match the laboratory results to clinical outcomes to gain an even deeper understanding of the procedure.

By understanding these underlying mechanisms, it is hoped that safer and more effective transplant options may be developed. Furthermore, it will enhance our understanding of the processes contributing to a successful AHSCT outcome and the best candidates for the procedure in people living with MS.

Progress to Date

Dr Visweswaran has successfully designed metabolic flow cytometry panels, and optimised antibodies and experiment conditions for these flow cytometry panels. Additionally, she has designed flow cytometry panels to measure mitochondrial activity, mitochondrial superoxide generation and glucose uptake rates. These methodologies will determine any changes to the metabolic profile of immune cells in MS before and after AHSCT and compare them to a non-autoimmune cohort of people with non-Hodgkin’s lymphoma who have also undergone AHSCT, and people who do not have either condition.

In preliminary work, Dr Visweswaran has found that people living with MS had high metabolic activity in some immune cells early after AHSCT treatment. This may be due to the large growth and expansion of immune cells because of the reduction in white blood cells, which occurs after treatment.

She next plans to look at the link between increased metabolic activity and long-term clinical outcomes to determine if the high metabolic state early after treatment could predict subsequent clinical outcomes.

Dr Visweswaran also found major differences in the level of metabolic markers across various immune cells, which may play a role in regulating their fate and function.

Dr Visweswaran is currently preparing several review and scientific articles to be published in scientific journals and has presented this work at national conferences.

Updated 31 March 2023

Updated: 19 January, 2021

Stages of the research process

Fundamental laboratory
Research

Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.

Lab to clinic timeline: 10+ years
Translational
Research

Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.

Lab to clinic timeline: 5+ years
Clinical Studies
and Clinical Trials

Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.

Lab to clinic timeline: 1-5 years

Investigator

Grant Awarded

  • Post-Doctoral Fellowship

Total Funding

  • $165,000

Duration

  • 3 years

Funding Partner

  • The Neil and Norma Hill Foundation
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Changes in the immune system following AHSCT