Michael Huang, the NHMRC Peter Doherty Postdoctoral Fellow in the department of pathology, Bosch Institute, at the University of Sydney, Australia, was awarded an MDA development grant totaling $177,100 over a period of three years to explore how deficiency of the frataxin protein in Friedreich’s ataxia (FA) may alter the function of cellular power supplies called mitochondria.
The work could lead to novel and accessible therapeutic strategies in FA.
A short description of Michael Huang’s current research:
Friedreich’s ataxia is a rare but severe childhood condition that is characterized by the death of vital cells of the central nervous system and heart. This renders patients (often still in childhood or at puberty) wheelchair-bound, with many succumbing to heart failure in their 30s. Patients require lifelong medical support, and unfortunately, there is currently no cure.
FA is caused by a severely reduced amount of a protein called frataxin. Frataxin performs vital tasks in the cellular “powerhouse,” the mitochondrion, which produces energy for cells.
My studies identified mitochondrial defects in tissues lacking frataxin. As the heart and the nervous system rely heavily on mitochondria to fulfill their energy demands, they are most affected by mitochondrial dysfunction. I will examine the extent that frataxin deficiency disrupts mitochondrial homeostasis and the possibility of targeting this process as a therapy.
Mitochondria constantly undergo fusion or division according to energy demands. As previous studies have shown proliferation of damaged mitochondria in frataxin-deficient cells, I will explore alterations in the ability for mitochondria to fuse or divide in our cardiac- and neural-specific mice models of FA. Further, I will assess the pathological changes in the synthesis and maintenance of mitochondria in FA.
Importantly, based on my recent exciting results, I will investigate the mechanism of how vitamin B3 can boost mitochondrial health to prevent the pathology in FA through its ability to affect mitochondrial dynamics, biogenesis and clearance.
Degeneration of tissues highly dependent on the mitochondrion as an energy source (e.g., neurons, cardiomyocytes) is a feature shared by FA and other neuromuscular disorders caused by defective mitochondrial proteins. Thus, a clear understanding of alterations in mitochondrial homeostasis is vital for elucidating the pathogenesis of these diseases. The potential of vitamin B3 to boost mitochondrial function could lead to novel and accessible therapeutic strategies.
Is this your first MDA grant?
This is the first MDA grant that I have received as the principal investigator. This Development Grant will be fundamental to my development and transition into an independent researcher in Friedreich’s ataxia and neuromuscular diseases. Importantly, this grant provides the critical funding to conduct my independent research and develop my area of specialty.
What inspired you to study FA?
Friedreich’s ataxia is a serious disorder that progressively robs people of their way of life. I am passionate about making a difference to the lives of people affected by Friedreich’s ataxia, as I have seen first-hand the terrible consequences of the disease. I believe my research will make a substantial, long-term difference to the future lives of children and adults.
What is your area of focus within the FA field, and why is it important?
While studying the pathogenesis of Friedreich’s ataxia, I have developed a strong interest in the involvement of the mitochondrion. This is because of its multifaceted involvement in aging and development of diseases. Therefore, insights gained from understanding the mitochondrial biology will be beneficial to understanding not only Friedreich’s ataxia but also other important human disorders.
The mitochondrion is a vital part of life, where its dysfunction or damage has widespread ramifications on the health of an organism. This is clearly demonstrated in not just Friedreich’s ataxia but also other devastating human genetic disorders that are caused by mitochondrial dysfunction. Indeed, striking similarities can be drawn between these different disorders, with mitochondrial dysfunction being the common denominator. Therefore, it is imperative to increase our understanding of the mitochondrial biology and its role in causing human conditions.
What is the expected outcome of this research — what will we learn, or what will be accomplished?
This research aims to comprehensively elucidate the effects of Friedreich’s ataxia in terms of mitochondrial biology. This aspect is vastly overlooked and insufficiently investigated in FA, where greater understanding can lead to novel therapeutic strategies. Using our advanced mouse models of Friedreich’s ataxia, a new and rationalized therapy involving vitamin B3 that targets mitochondrial biology will be examined in detail.
Why is it important that MDA continue to fund research in FA?
Friedreich’s ataxia is a devastating disorder that currently has no cure. MDA funding received by my advisor’s (Des Richardson) laboratory in the past culminated in seminal findings that significantly increased our understanding of the pathogenesis of Friedreich’s ataxia. Continual support from MDA will undoubtedly lead to further important findings that will benefit the scientific community and the patients directly.
To learn more about how MDA research is accelerating treatments and cures for FA, please visit mda.org.
Help MDA continue to fund groundbreaking research to fight Friedreich’s ataxia and other muscle debilitating diseases.
