New biomarkers for Huntington’s disease hint at disease progression
Researchers at Stanford University School of Medicine have identified several new biological markers to measure the progression of the inherited neurodegenerative disorder Huntington’s disease.
The genetics underlying Huntington’s disease are well-understood. A rogue sequence in the gene that encodes for huntingtin protein results in the production of a mutant form that aggregates and damages cells. Patients display a progressive loss of voluntary and involuntary movements, as well as psychiatric and cognitive disturbances, and usually die 10-15 years after its onset.
But knowing the genetics is not enough. While genetic testing can diagnose the condition before symptoms appear, there are still no pharmacological treatments that can prevent or ameliorate the disease. A few drugs have shown promise in cell culture or animal models, but clinical trials in humans are time consuming because of the slow onset and progression of the disorder’s clinical symptoms. Moreover, researchers are unable to take biopsies of the brain to assess the effects of potential therapeutic compounds.
“We have identified several biomarkers that correlate with disease progression and treatment in mice,” says research leader Daria Mochly-Rosen, of Stanford University. Her team looked at one of the early events in Huntington’s progression, where the mutant protein aggregates disrut the function of cell mitochondria, lowering cellular energy levels and causing oxidative damage.
The team found that the levels of mitochondrial DNA, presumably released from dying neurons, were increased in the blood plasma of mice that were starting to develop the symptoms of the disease. In contrast, mitochondrial DNA levels decreased at later stages of the disease.
“We hope that our work will provide the basis for a larger study of patient samples that may ultimately identify biomarkers that can be used as surrogate markers to determine the benefit of therapeutic interventions in diagnosed but asymptomatic HD patients to prevent or delay disease onset,” says Mochly-Rosen.