MRV-funded research is uncovering new strategies to encourage reverted bone marrow cells to grow and replace defective ones

For most patients with inherited Bone Marrow Failure Syndromes, the condition is incurable. Without treatment, their bone marrow cannot make the blood and platelet cells their body needs.

However, a small number of inherited Bone Marrow Failure Syndrome patients experience a natural reversal of their symptoms, which is called spontaneous revertant mosaicism.

Dr Parvathy Venugopal, a Maddie’s Vision Fellowship recipient and member of our Centre of Research Excellence, is investigating this phenomenon in patients to find strategies to encourage reverted bone marrow cells to grow and replace defective ones.

A second stream of this study describes a mouse model for bone marrow failure that can be used to research the potential for transplantation of corrected cells as a therapy for Bone Marrow Failure Syndromes.

“In my research, supported by the Maddie Riewoldt’s Vision Research Fellowship, we detected spontaneous revertant mosaicism in 25% of individuals with MECOM-associated syndrome – an inherited Bone Marrow Failure Syndrome with varied presentation usually characterised by platelet deficiency and bone abnormalities,” Dr Venugopal said.

“Through detailed analysis of our patient cohort, we also found clinical features that were previously under-recognised in these individuals.

“We also established and characterised a mouse model for GATA2-deficiency syndrome, another inherited bone marrow failure where patients often present with immunodeficiency and/or leukaemia,” she continued.

“The model we developed showed similar features to human disease and revealed additional clinical features that were likely overlooked in patients due to the severity of immunity/leukaemia-associated symptoms.

“We are now using this model to test various conditions to help maximise disease correction while minimising transplant-related toxicity for patients,” Dr Venugopal added.

In work recently published in Nature, the team also discovered that PROX1, a gene regulated by GATA2, previously known to control lymphatic vessel development, also influences blood cell production.

The findings of their study suggest that lymphatic vessels may serve as an unexpected source of blood cells during both normal development and disease.

The following steps for this research involve trying to understand what causes lymphatic vessels to produce blood cell types and whether this process can be manipulated to benefit patients.

The research that Maddie’s Vision has supported has resulted in Dr Venugopal acquiring an incredible $5 million of leveraged funding as part of a national team working towards further research into rare inherited disorders.

Maddie’s Vision is thrilled that Dr. Venugopal has been able to leverage her initial Maddie’s Vision fellowship to gain additional grant funds to help her and her team shed further light on developmental and disease processes.