Novel Imaging Biomarkers for Huntington’s Disease and Other Hereditary Choreas

Abstract

Purpose of the ReviewImaging biomarkers for neurodegenerative disorders are primarily developed with the goal to aid diagnosis, to monitor disease progression, and to assess the efficacy of disease-modifying therapies in support to clinical outcomes that may either show limited sensitivity or need extended time for their evaluation. This article will review the most recent concepts and findings in the field of neuroimaging applied to Huntington’s disease and Huntington-like syndromes. Emphasis will be given to the discussion of potential pharmacodynamic biomarkers for clinical trials in Huntington’s disease (HD) and of neuroimaging tools that can be used as diagnostic biomarkers in HD-like syndromes.Recent FindingsSeveral magnetic resonance (MR) and positron emission tomography (PET) molecular imaging tools have been identified as potential pharmacodynamic biomarkers and others are in the pipeline after preclinical validation. MRI and 18F-fluorodeoxyglucose PET can be considered useful supportive diagnostic tools for the differentiation of other HD-like syndromes.SummaryNew trials in HD have the primary goal to lower mutant huntingtin (mHTT) protein levels in the brain in order to reduce or alter the progression of the disease. MR and PET molecular imaging markers have been developed as tools to monitor disease progression and to evaluate treatment outcomes of disease-modifying trials in HD. These markers could be used alone or in combination for detecting structural and pharmacodynamic changes potentially associated with the lowering of mHTT.

Drug-Resistant Epilepsy in Children with Juvenile Huntington's Disease: A Challenging Case and Brief Review

“… 21 Spectroscopy and brain positron emission tomography scans might provide a promising biomarker by enabling the early detection of abnormal striatal glucose metabolism. 22 Studies demonstrated that these neuroimaging changes occurred before the emergence of clinical symptoms. 23 Nevertheless, not much is known about typical MRI findings in JHD.…”

Huntington’s Disease: A Review of the Known PET Imaging Biomarkers and Targeting Radiotracers

“…Although considerable progress has been made towards identifying some of the mechanisms involved in the HD pathogenesis, there are currently no disease-modifying strategies available [6]. The uncovering of the huntingtin (htt) mutation in 1993 has enabled intensified research efforts with the hope to slow down or stop progressive neuronal damage [4]. HD is an autosomal dominant disease of the central nervous system (CNS) caused by an expansion of the CAG sequence in the huntingtin gene (HTT), located on chromosome 4 [3,7].…”

“…It has been proposed that a flawed proteostasis network results from the aggregation of mHTT, initiating a cascade of devastating consequences for synchronised neuroreceptors [8]. Individuals with 7-12 CAG tracts are usually considered healthy, whilst those with 35 suffer from HD [4]. Additionally, full penetrance and consequently, rapid progression of the disease, is associated with more than 40 repeats [9].…”

“…It progresses with fatal and devastating psychiatric, cognitive and motor impairments, caused by mutant huntingtin (mHTT) protein expression. Some excellent reviews on the molecular imaging of HD have been published, however focusing primarily on clinical data [2][3][4][5]. This review is divided according to HD biomarkers thought to be most affected by the pathology.…”

Kinfitr — an open-source tool for reproducible PET modelling: validation and evaluation of test-retest reliability

“…Positron emission tomography (PET) is an imaging modality with high sensitivity and specificity for biochemical markers and metabolic processes in vivo [ 1 ]. It is an important tool in the study of psychiatric and neurological diseases, as well as for evaluating novel and established pharmacological treatments [ 2 – 4 ]. In PET imaging, study participants receive an intravenous injection of a radioligand, which binds specifically to a target molecule [ 5 ].…”