The updated development of blood-based biomarkers for Huntington’s disease

Abstract

Huntington’s disease is a progressive neurodegenerative disease caused by mutation of the huntingtin ( HTT ) gene. The identification of mutation carriers before symptom onset provides an opportunity to intervene in the early stage of the disease course. Optimal biomarkers are of great value to reflect neuropathological and clinical progression and are sensitive to potential disease-modifying treatments. Blood-based biomarkers have the merits of minimal invasiveness, low cost, easy accessibility and safety. In this review, we summarized the updated development of blood-based biomarkers for HD from six aspects, including neuronal injuries, oxidative stress, endocrine functions, immune reactions, metabolism and differentially expressed miRNAs. The blood-based biomarkers presented and discussed in this review were close to clinical applicability and might facilitate clinical design as surrogate endpoints. Exploration and validation of robust blood-based biomarkers require further standard and systemic study design in the future.

Perinatal Tissue-Derived Stem Cells: An Emerging Therapeutic Strategy for Challenging Neurodegenerative Diseases

“…Zuccato and colleagues found no difference in the BDNF levels in serum and plasma in a large cohort of patients [129]. Other studies with plasma samples have confirmed this finding [130,131] and further detected no significant associations between the plasma BDNF and clinical signs of HD [132,133]. Overall, the current evidence does not support the value of BDNF as a robust biomarker of HD.…”

Validation of remote collection and quantification of blood Neurofilament light in neurological diseases

“…NfL could have several applications in therapeutic development and clinical management in neurology. NfL has been proposed as a potential surrogate endpoint indicating neuroprotection for multiple neurological disorders (e.g., MS (48)(49)(50), ALS (51)(52)(53), and HD (10,54,55)); its utility as a safety biomarker for neurotoxicity is also being considered (56,57); and in the future NfL might be used for enrichment and stratification of presymptomatic populations to facilitate the design of prevention trials (10,54,55). However, before NfL measurements can be validated for either intended use, there needs to be deep characterisation of its natural fluctuations throughout the progression of each disease.…”

The characteristic and prognostic role of blood inflammatory markers in patients with Huntington’s disease from China

“…It usually begins to manifest in mid-adulthood and lasts for about 15–20 years ( 2 , 3 ). To date, there are no effective disease-modifying therapies, imposing a heavy economic burden on families and society which increases as the disease progresses ( 4 ). Although the complete pathogenesis of HD is not yet fully understood, several potential mechanisms have been proposed, such as excitotoxicity, dopaminergic imbalance, mitochondrial dysfunction, metabolic defects, disruption of proteostasis, transcriptional dysregulation, and neuroinflammation ( 5 ).…”