The research of Margherita Milone, M.D., Ph.D., focuses on muscular dystrophies and mitochondrial disorders causing muscle weakness. Mitochondrial disorders can affect muscles alone or muscles and other organs. These disorders are due to dysfunction of the mitochondria, organelles that produce energy.

Mitochondria have their own DNA, which is inherited from the mother, but their correct function also depends on nuclear genes located outside the mitochondria. Therefore, mitochondrial diseases can be due to primary defects of the mitochondrial DNA or defects in genes of the nuclear DNA.

The main goal of Dr. Milone's research activity is to identify the genetic defect responsible for the disease of individual patients, especially when patients present with unusual clinical features. By correlating clinical, electromyography (EMG) and muscle biopsy findings, and genetic defects of different patients, one can learn more about these disorders and have a better understanding of the disease mechanisms, which in turn can open avenues to future treatments.

Focus areas

• Characterization of a specific muscular dystrophy due a gene called ANO5, which causes proximal leg and arm weakness and/or inability to stand on toes
• Search of the nuclear gene defects causing mitochondrial disease in patients with mitochondrial disorders who have no primary mutations of the mitochondrial DNA, but have a defect in genes essential for mitochondrial DNA proper function
• Characterization of muscle diseases associated with abnormal muscle irritability causing involuntary muscle twitching or rippling

Significance to patient care

The results of Dr. Milone's research, to which patients are major contributors, translate into clinical practice. For example, the identification of amyloid deposits (accumulation of abnormal protein that stains red) in the muscle of some patients with ANO5-muscular dystrophy led to the correct diagnosis in patients with muscle disease of unknown type.

The identification of a nuclear gene defect in a woman with mitochondrial disease allows reliable estimation of the risk of inheritance of the disease, relieving the unnecessary stress that all her children will be at risk of developing disease.