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HomemifeatureAccelerating Knowledge MDFA Research Grants

Accelerating Knowledge MDFA Research Grants

This month, Macular Disease Foundation Australia (MDFA) will announce funding for several deserving research projects. These grants are made possible through the generous contributions of the Australian macular disease community.

MDFA has a proud track record supporting innovative clinical research programs. Between 2011 and 2021, the not-for-profit organisation has supported 29 separate projects with a total funding pool of $5.1 million.

These exciting research grant awards… support innovative and ground-breaking research that will bring significant benefit to the many people with macular disease

In this article, Chris James, MDFA’s Research and Policy Manager, reviews research projects that have recently come to fruition with MDFA grant support.

The impact of MDFA’s research program can perhaps best be illustrated by the work of Professor Alice Pébay, University of Melbourne, who was awarded funding from the 2017 grants round. In a recent publication,1 Professor Pébay and her extensive team uncovered novel genes and pathways most likely involved in geographic atrophy and provided a new experimental model that can be applied to the study and treatment of other complex diseases.

Professor Pébay said without funding from MDFA’s Research Grants Program, the cross-disciplinary project would never have commenced.

“MDFA understands the fundamental importance of investing in national grassroot research for supporting innovative and impactful research,” she observed.

The early funding also positioned the researchers to secure additional grants, including from the Ophthalmic Research Institute of Australia, the National Health and Medical Research Council, and the Medical Research Future Fund.

Supporting Blue Sky Research

Another MDFA-funded research program to reach fruition in 2022 was led by Dr Anai Gonzales Cordero, from the Children’s Medical Research Institute, University of Sydney. Dr Gonzales Cordero was one of the first researchers to receive financial support from the Grant Family Fund, which supports innovative ‘blue sky’ research into macular disease by early career researchers.

Dr Gonzalez Cordero spent over a year diligently preparing for a single experiment, a “brief moment” of research gold. Her goal was to create a macula-containing organoid, or ‘mini organ’, in half a day. The ‘macula in a dish’ could then be translated into a source of cells for replacement therapies and to test the efficacy of potential treatments in the future.

One of the exciting potential outcomes of this research is the possibility of creating a ‘macular patch’ for people with age-related macular degeneration (AMD). Such a transplant could replace the photoreceptor cells lost from the retina and effectively restore macular function and sight.

Dr Gonzalez Cordero says with this, research scientists could generate a macular patch over the next five to 10 years.

The newly-developed technique will also give researchers the opportunity to work with actual human eye cells. Vision has been successfully rescued in blind mice in the past. With this new mini organ, researchers now have an opportunity to aim for the same in humans.

“The Grant family has vision. They want to fund novel ideas. This sort of creativity and new ideas and research wouldn’t be funded otherwise,” Dr Gonzalez Cordero noted.

Novel Treatment Approaches

Two additional projects recently concluded, with significant progress made on the theme of novel treatment approaches.

Dr Yvette Wooff and colleagues from the Australian National University investigated extracellular vesicles – bubble-like structures containing messenger molecules – that cells use to exchange information about their wellbeing and health. In diseases such as AMD, these extracellular vesicles, and the cellular messages within, can become lost or miscommunicated, leading to pathological levels of cellular stress and eventual cell death.

“My work, funded by the MDFA, has focussed on understanding what these essential messages are supposed to say and to harness them as a novel therapy for the treatment of AMD,” explained Dr Wooff.

“My research uncovered important molecules within these vesicles and showed that by delivering them to the retina we can prevent retinal cell death. By harnessing the molecular messages of retinal health, I aim to restore communication between cells and slow the progression of disease.”

This work has contributed to three industry partnerships with manufacturing/ therapeutic companies, two provisional patents (one filed, one underway) and a successful Cooperative Research Centres Projects grant with VivaZome Therapeutics (Melbourne) to enable the translational development of this work.

Dr Ting Zhang and colleagues from the Save Sight Institute, University of Sydney, recognised that metabolic dysfunction plays an essential role in the development and progression of photoreceptor degeneration in AMD.

Disruptions in the de novo serine synthesis pathway impact mitochondrial function in Müller cells, rendering the macula more susceptible to oxidative and mitochondrial stress than cells from the peripheral retina.

Dr Zhang explained how she “established a lipid nanoparticle-based drug delivery system that delivers RNA encoding for the key enzyme – phosphoglycerate dehydrogenase – into Müller cells and raised the level of this protein with the help of a CRISPR gene activation system”. Further testing has demonstrated the protective effects of this intervention in macular cells in vitro, pointing towards a therapeutic benefit of the approach.

These two exciting research projects by Dr Wooff and Dr Zhang have laid the groundwork for progressing these treatment approaches toward future human clinical trials in macular disease.

2023 Grant Awards

Submissions for the 2023 Macular Disease Foundation Research grants and Grant Family Fund grants are currently being reviewed.

New to the 2023 Research Grants program is the inclusion of macular disease community members in the review process. Their effort is expected to complement and support rigorous peer review.

Additionally, it is expected to increase engagement of the macular disease community in MDFA’s research program, bringing perspectives into the decision to fund research that reflects the long-term needs of people afflicted by macular conditions.

Dr Kathy Chapman, MDFA CEO, highlighted the importance of this work. “These exciting research grant awards represent Macular Disease Foundation Australia’s ongoing commitment, with the generous support of our community, to support innovative and ground-breaking research that will bring significant benefit to the many people with macular disease.”

The 2023 grant recipients will be announced at a ceremony on Friday 16 June 2023 at Admiralty House, Sydney – the official residence of the Governor-General.

For more information visit: mdfoundation.com.au/research/mdfa-funded-research/funded-projects.

Chris James is the Research and Policy Manager at Macular Disease Foundation Australia. He has a Masters in Immunology and 16 years’ pharmaceutical experience, including nine years in ophthalmology.

Reference
1. Senabouth A., Daniszewski M., Lidgerwood G.E. et al.Transcriptomic and proteomic retinal pigment epithelium signatures of age-related macular degeneration. Nature Communications 2022; 13: 4233. doi: 10.1038/s41467-022-31707-4.