Summary of Study ST002442
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001573. The data can be accessed directly via it's Project DOI: 10.21228/M8CD9V This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST002442 |
| Study Title | Alterations in CSF Urea Occur in Late Manifest Stage Huntington Disease |
| Study Type | untargeted metabolomics analysis |
| Study Summary | Huntington Disease (HD) is a neurodegenerative disorder caused by expanded cytosine-adenine-guanine (CAG) repeats in the Huntingtin gene, resulting in the production of mutant huntingtin proteins (mHTT). Previous research has identified urea as a key metabolite elevated in HD animal models and post-mortem tissues of HD patients. The exact timing of these elevations in urea and the molecular mechanism(s) responsible for these disturbances remain unknown. To better understand the pathophysiologic mechanisms responsible for elevations in urea in HD, we completed a global metabolomic profile of cerebrospinal fluid (CSF) from individuals who were at several stages of disease: pre-manifest (PRE), manifest (MAN), and late-manifest (LATE) HD participants compared to controls. We found approximately 500 metabolites were significantly altered in pre-manifest participants compared to controls, although no significant difference in CSF urea or urea metabolites. Interestingly, CSF urea was only significantly elevated in LATE participants compared to controls. There were no changes in the urea metabolites, citrulline, ornithine and arginine throughout disease; however, we did observe changes in acetate, creatinine, 4-acetamidobutanoate and 4-aminobutyraldehyde which are indirect modifiers of urea. Overall, our study confirms that elevations in urea do occur in HD, albeit later in disease and that these changes may reflect more central impairments to cellular energy metabolism yet to be explored. |
| Institute | Vanderbilt University |
| Department | Chemistry |
| Laboratory | Center for Innovative Technology |
| Last Name | CODREANU |
| First Name | SIMONA |
| Address | 1234 STEVENSON CENTER LANE |
| SIMONA.CODREANU@VANDERBILT.EDU | |
| Phone | 6158758422 |
| Submit Date | 2023-01-12 |
| Num Groups | 4 |
| Total Subjects | 60 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Thermo) |
| Analysis Type Detail | LC-MS |
| Release Date | 2023-01-25 |
| Release Version | 1 |
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Collection:
| Collection ID: | CO002524 |
| Collection Summary: | CSF samples were collected from 60 participants as part of the CHDI HD-Clarity study. There were 16 PRE, 16 MAN, 16 LATE HD participants and 12 control participants. Disease stage was determined using the diagnostic confidence level (DCL), length of CAG expansion and burden of pathology calculated from (CAG expansion – 35.5) x Age. Control participants were individuals without a known history of Huntington Disease (HD). All HD participants have a CAG expansion of > 40. PRE participants were not motor manifest as indicated by a DCL of <4 and a burden of pathology of > 250. MAN participants had a DCL =4 and a total functional capacity (TFC) between 7-13. The LATE group had all the above criteria for MAN and a TFC score between 0-6. Repeat CSF and blood samples collected 4-8 weeks after a baseline (BL) visit are provided for all control and PRE participants. Participants’ age and gender are reported here. Three participants (2 PRE, 1 MAN) were taking supplemental vitamins; however, their metal levels were similar to those in their corresponding participant group and thus, the data from these participants are included. Basic demographics like age and gender were reported previously in addition to participants' scores on a battery of cognitive, behavioral and motor assessments including the symbol digit modality test (SDMT), Stroop Word Reading (SWR), total functional capacity (TFC), total motor score (TMS) and the recently developed cUHDRS. |
| Collection Protocol Filename: | Sample_Collection.pdf |
| Sample Type: | CSF |
| Storage Conditions: | -80℃ |
