Researchers successfully attenuated the import defect and subsequent neuronal death, as well as significantly restored mitochondrial activity, by overexpression of TIM23 subunits. This work carries significant implications for protein import-based therapies in the treatment of Huntington’s Disease.
Description
Mitochondrial dysfunction has been highlighted as a critical driver of Huntingdon’s Disease (HD) pathophysiology. Though the genetic cause of HD is known, the pathogenic mechanism is still unclear. At present, there is no treatment that slows the progression of HD. Restoration of the mitochondrial function is a promising therapeutic approach. University of Pittsburgh researchers have identified an interaction between mutant huntingtin (muHtt) protein and a mitochondrial transport protein complex TIM23. The investigators demonstrated that binding of muHtt to TIM23 inhibits mitochondrial protein import. This results in mitochondrial dysfunction, which leads to neuronal dysfunction and cell death, driving disease progression. The mitochondrial protein import malfunction occurs very early in the development of Huntington’s Disease, making it an attractive therapeutic target.
Applications
• Gene therapy to treat Huntington’s Disease
• Development of therapies to treat other diseases caused by mitochondrial protein import defects
• Research tool to study mitochondrial transport
Advantages
• Therapeutic target represents an early stage in disease development, allowing an early intervention before symptoms worsen
• Significant increase in mitochondrial activity of neuronal cells with mutant Htt gene
• Inhibition of mutant Htt-mediated neuronal death
Invention Readiness
Proof of principle was demonstrated in-vitro in neuronal cells isolated from transgenic HD mice.
IP Status
https://patents.google.com/patent/US10525108B2
