Fast Tracking A Novel Therapy To Prevent Mito-Related Blindness

The Problem

Mitochondria are the power houses of the cell providing the body with over 90% of the energy it needs to sustain life. In a person with mitochondrial disease (mito), the mitochondria do not work properly due to defects in genes controlling mitochondrial function. Impaired mitochondrial energy supply causes multiple organs to malfunction or fail.

Mitochondrial Optic Neuropathies (MONs) are a group of mitochondrial diseases causing degeneration of specialised cells in the retina, known as retinal ganglion cells, leading to vision impairment and eventual blindness. Currently, there are no cures for MONs or any form of mito and only limited therapeutic strategies are available.

One of the most promising therapeutic avenues for inherited diseases, including mito, is gene therapy whereby defective genes are replaced with ‘correct’ gene copies, reinstating proper mitochondrial function. Given the vastly complex nature of mitochondrial genetics and biology however, the application of gene-dependant therapies in mito is currently very limited. As such, therapeutic strategies that provide alternate or complementary approaches to gene therapy are highly desirable in the fight against mito.

Alessia Indrieri pic
Our Solution

Dr Alessia Indrieri and her team are developing a novel strategy for treating MONs that does not rely on targeting a specific MONs-related gene or mutation. Instead, they have identified two ‘master controllers’ of mitochondrial function and survival in retinal cells, known as microRNAs (miRNAs) ‘miR-181a and b’. They can increase or decrease the expression of other critical genes required for normal mitochondrial processes in the retina.

Dr Indrieri and her team hypothesise that reducing the activity of these miRNAs may prevent mitochondrial decline in retinal ganglion cells, thereby preventing retinal cell degeneration and reducing vision loss. The team will test this therapeutic strategy in a mouse model and a patient-derived retinal cell ‘organoid’ that model two of the most common forms of MONs, Leber Hereditary Optic Neuropathy (LHON) and Dominant Optic Atrophy (DOA).

If successful, this research will provide a novel, geneindependent therapeutic product that may ultimately prevent or significantly delay the onset of blindness in individuals affected by MONs.

The Next Step

Therapeutic strategies using microRNAs are becoming a promising reality as shown by several ongoing clinical trials around the world currently investigating their efficacy and safety.

This ground-breaking project will test the efficacy of miR-181a/b as a new therapeutic strategy for MONs and for the development of an RNA-based therapeutic product to translate into human clinical trials.

To proceed, we seek funding to the value of $300,000 (or $150,00 per year over two years) to facilitate:

Personnel fees - $162,000 or $81,000/year
• Salary of a postdoctoral researcher: $45,000/year
• Salary of a technician: $36,000/year

Supplies - $138,000 to cover:
• Animal costs: $20,000
• Consumables: $100,000
• Equipment: $18,000

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The Outcome

Life-limiting symptoms such as blindness may be greatly reduced in patients that currently have extremely limited treatment options.

If proven successful, this therapy has potential for far broader impact and application across many forms of mito, and other common neurodegenerative diseases such as Parkinson’s Disease and Glaucoma, where mitochondrial dysfunction plays a critical role.

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Become A Mito Research Partner

As a Mito Research Partner, you will enable world class research to get off the ground with your full donation going towards the project you choose to support. Give hope to the mito community by fast-tracking the medical advancements they so desperately need.

You will receive regular updates on how your
research project is breaking new ground and, where possible, have the opportunity to meet the researchers and clinical experts.

For more information on how you can contribute to this exciting project, contact: Michel Zwecker, Development Manager   P: 02 8033 4113 or 0411 883 213     E: michel.zwecker@mito.org.au 

Dr. Alessia Indrieri
Principal Investigator at the Telethon Institute of Genetics Medicine (TIGEM), Pozzuoli, Italy.

Dr. Indrieri has focused her studies on mitochondrial disorders and has acquired a strong expertise in the biology of non-coding RNA and in their application in disease therapy. Her current focus is to develop and validate new therapeutic strategies to treat mitochondrial-associated neurodegeneration in a mutation-independent manner.

“If successful, miRNA therapy might be available as a valid treatment option to patients within a few years."