KineMed, Inc. and CHDI Foundation, Inc. have announced a collaboration to use KineMed’s isotopic labeling and dynamic proteomics platform to investigate the turnover rates of huntingtin protein, a mutant form of which plays a central role in the pathogenesis of Huntington’s disease (HD).
There are currently no therapeutics approved that can slow the progression of HD, an inherited neurodegenerative disorder that affects about 30,000 people in the United States, with up to 150,000 additionally at risk of developing the disease.
HD patients have a genetic variation that causes the production of a mutant huntingtin protein with an expanded region of polyglutamine (polyQ) amino acids.
The expanded huntingtin protein leads to the degeneration of brain cells, with disease severity related to the size of the expansion.
The clinical signs of disease are behavioral, cognitive, and motor impairments that, over the course of the disease, significantly reduce the individual's quality of life and ultimately cause death within 15 to 25 years of overt motor symptom onset.
KineMed’s uniquely sensitive tandem mass spectrometric technology will be used in this collaboration to measure in vivo dynamics of the huntingtin protein, including protein half-life and synthesis rate.
This proprietary measurement approach will allow assessment of the rate of metabolism of huntingtin protein as a function of polyQ length and whether investigational drugs are affecting its production and clearance.
“The application of KineMed’s technology will provide us with unique insights into central nervous system disease pathophysiology,” said Seung Kwak, PhD, Director, Target Biology at CHDI.
Kwak continued, “We are excited and hopeful that this collaboration will help define the dynamics of the mutant protein in disease-relevant tissues, and ultimately help measure therapeutic efficacy for Huntington’s disease.”
“We are delighted to continue our collaboration with CHDI in an area that leverages our capabilities to understand the biology of neurodegenerative diseases with complex phenotypes,” said Scott Turner, PhD, Executive Vice President of Research and Development at KineMed.
Turner continued, “This deeper understanding ultimately contributes towards targeting mechanisms at the core of the disease pathway, accelerating the development of therapeutics that can provide real hope for Huntington’s patients.”
KineMed’s techniques have also been applied to investigate other pathways such as microtubule dynamics, mitochondrial turnover and axonal transport which are involved in HD and other neurodegenerative diseases.