A biological classification of Huntington's disease: the Integrated Staging System

Tabrizi, Sarah J.; Schobel, Scott; Gantman, Emily Conn; Mansbach, Alexandra; Borowsky, Beth; Konstantinova, Pavlina; Mestre, Tiago; Panagoulias, Jennifer; Ross, Christopher A.; Zauderer, Maurice; Mullin, Ariana P.; Romero, Klaus; Sivakumaran, Sudhir; Turner, Emily C.; Long, Jeffrey D.; Sampaio, Cristina

doi:10.1016/s1474-4422(22)00120-x

Cited by 100 publications

(68 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Irrespective of the mechanism(s) possibly linking mHTT to SNORD13 and the source of this snoRNA (currently unknown), we can speculate that the increase in the plasma level of SNORD13 in patients with HD may peripherally report a ‘tipping point’ in the pathogenic cascade at the neuronal level, while normal levels may mark a ‘molecular pre-manifest status’ in disease evolution. In fact, when we used published data [ 2 ] on CSF mHTT and plasma or CSF NfL as benchmarks to compare the performance of plasma SNORD13, we found that it outperformed both CSF mHTT and plasma or intrathecal NfL as a reporter of overt HD, supporting its potential value as a peripheral cue of central pathogenic processes ( Table 3 ) In a clinical context circulating SNORD13 does not have a predictive value, being absent in pre-HD; however, this easily measurable, inexpensive and reliably quantifiable test (it is consistent, accurate, sensitive, specific, and reproducible) [ 9 ] may be useful to better catch, on a laboratory basis, the shift from prodromal to overt HD [ 30 ]. This may be useful to stratify and select candidate patients for clinical trials and to aim at disease-specific pathophysiological cascades.…”

Section: Discussionmentioning

confidence: 99%

Circulating U13 Small Nucleolar RNA as a Potential Biomarker in Huntington’s Disease: A Pilot Study

Romano

Peconi

et al. 2022

IJMS

View full text Add to dashboard Cite

Plasma small RNAs have been recently explored as biomarkers in Huntington’s disease (HD). We performed an exploratory study on nine HD patients, eight healthy subjects (HS), and five psychiatric patients (PP; to control for iatrogenic confounder effects) through an Affymetrix-Gene-Chip-miRNA-Array. We validated the results in an independent population of 23 HD, 15 pre-HD, 24 PP, 28 Alzheimer’s disease (AD) patients (to control the disease-specificity) and 22 HS through real-time PCR. The microarray results showed higher levels of U13 small nucleolar RNA (SNORD13) in HD patients than controls (fold change 1.54, p = 0.003 HD vs. HS, and 1.44, p = 0.0026 HD vs. PP). In the validation population, a significant increase emerged with respect to both pre-HD and the control groups (p < 0.0001). SNORD13 correlated with the status of the mutant huntingtin carrier (r = 0.73; p < 0.001) and the disease duration (r = 0.59; p = 0.003). The receiver operating characteristic (ROC) curve analysis showed the high accuracy of SNORD13 in discriminating HD patients from other groups (AUC = 0.963). An interactome and pathway analysis on SNORD13 revealed enrichments for factors relevant to HD pathogenesis. We report the unprecedented finding of a potential disease-specific role of SNORD13 in HD. It seems to peripherally report a ‘tipping point’ in the pathogenic cascade at the neuronal level.

show abstract

Section: Discussionmentioning

confidence: 99%

Circulating U13 Small Nucleolar RNA as a Potential Biomarker in Huntington’s Disease: A Pilot Study

Romano

Peconi

et al. 2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Stage 1 is verified with measurable indicators of underlying pathophysiology (biomarkers) but still asymptomatic. Stage 2 adds any sign or symptom to stage 1 and stage 3 includes symptomatic patients with loss of functionality in their activities of daily living [42].…”

Section: Prodromal Hdmentioning

confidence: 99%

Review of Huntington’s Disease: From Basics to Advances in Diagnosis and Treatment

et al. 2022

View full text Add to dashboard Cite

We conducted the present review facing the enormous growth of scientific knowledge in Huntington's disease (HD) and the need for a practical update for general neurologists. HD is a devastating neurodegenerative disease of autosomal dominant inheritance and full penetrance, caused by an expansion of the cytosine-adenine-guanine (CAG) trinucleotide in the huntingtin gene located on chromosome 4. The clinical phenotype varies according to the age of presentation, but it is mainly characterized by cognitive, motor and psychiatric disturbances. Many mechanisms were raised trying to explain the path to neurodegeneration, including disruption of proteostasis, transcription and mitochondrial dysfunction as well as direct toxicity. There has been tremendous progress regarding disease pathogenesis, clinical management and promising new therapeutic avenues including disease-modifying treatments that pose a challenge and a need for a practical approach to be taken by movement disorders specialists and general neurologists.

show abstract

“…The use of disease onset as an endpoint in clinical trials would therefore require a large premanifest study population. However, an updated system, i.e., the Integrated Staging System (HD-ISS), has recently been introduced, which combines information from imaging with clinical signs and decline in daily function and better tracks disease progression, including pre-symptomatic and premanifest stages [ 19 ].…”

Section: Huntington Disease: An Opportunity To Seek Early Predictive ...mentioning

confidence: 99%

Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington’s Disease

Pellegrini

Bergonzoni

Perrone

et al. 2022

Genes

View full text Add to dashboard Cite

Whether as a cause or a symptom, RNA transcription is recurrently altered in pathologic conditions. This is also true for non-coding RNAs, with regulatory functions in a variety of processes such as differentiation, cell identity and metabolism. In line with their increasingly recognized roles in cellular pathways, RNAs are also currently evaluated as possible disease biomarkers. They could be informative not only to follow disease progression and assess treatment efficacy in clinics, but also to aid in the development of new therapeutic approaches. This is especially important for neurological and genetic disorders, where the administration of appropriate treatment during the disease prodromal stage could significantly delay, if not halt, disease progression. In this review we focus on the current status of biomarkers in Huntington’s Disease (HD), a fatal hereditary and degenerative disease condition. First, we revise the sources and type of wet biomarkers currently in use. Then, we explore the feasibility of different RNA types (miRNA, ncRNA, circRNA) as possible biomarker candidates, discussing potential advantages, disadvantages, sources of origin and the ongoing investigations on this topic.

show abstract

A biological classification of Huntington's disease: the Integrated Staging System

Cited by 100 publications

References 82 publications

Circulating U13 Small Nucleolar RNA as a Potential Biomarker in Huntington’s Disease: A Pilot Study

Circulating U13 Small Nucleolar RNA as a Potential Biomarker in Huntington’s Disease: A Pilot Study

Review of Huntington’s Disease: From Basics to Advances in Diagnosis and Treatment

Current Diagnostic Methods and Non-Coding RNAs as Possible Biomarkers in Huntington’s Disease

Contact Info

Product

Resources

About