scholarly journals Is TGF-β1 a Biomarker of Huntington’s Disease Progression?

2021 ◽  
Vol 10 (13) ◽  
pp. 3001
Author(s):  
Klaudia Plinta ◽  
Andrzej Plewka ◽  
Magdalena Wójcik-Pędziwiatr ◽  
Nikola Zmarzły ◽  
Marcin Rudziński ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Plasma Levels ◽  
Motor Dysfunction ◽  
Disease Stage ◽  
Control Group ◽  
Early Disease ◽  
Positive Correlations ◽  
Early Disease Stage ◽  
Tgf Β1

Huntington’s disease (HD) is an autosomal dominant genetic disease that can be divided into preclinical and symptomatic stages. Due to the diverse HD phenotype, there is an urgent need to identify markers that would independently assess its severity. The aim of this study was to evaluate the use of plasma levels of TGF-β1 in the assessment of HD severity. One hundred HD patients and 40 healthy volunteers were included in the study. All HD patients underwent neurological and cognitive function assessment. TGF-β1 levels were determined in the plasma of all patients. The correlations between TGF-β1 levels and clinical profile and HD severity were also investigated. In symptomatic patients, cognitive decline was demonstrated, while in preclinical patients, no symptoms were found. Plasma levels of TGF-β1 in HD patients did not differ significantly from the control group and did not change with the progression of the disease. In addition, TGF-β1 levels also did not correlate with the severity of motor dysfunction. Positive correlations between plasma TGF-β1 concentration and intensity of cognitive impairment were found, but only in the early disease stage. There was no clear benefit in assessing plasma TGF-β1 levels in HD patients as a marker of disease severity.

Disease stage and plasma levels of cytokines in Huntington's disease: A 2-year follow-up study

2017 ◽  
Vol 32 (7) ◽  
pp. 1103-1104 ◽  
Author(s):  
J.A. Bouwens ◽  
E. van Duijn ◽  
C.M. Cobbaert ◽  
R.A.C. Roos ◽  
R.C. van der Mast ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Plasma Levels ◽  
Disease Stage ◽  
Follow Up Study

scholarly journals The sleep and circadian problems of Huntington’s disease: when, why and their importance

2020 ◽  
Author(s):  
Z. Voysey ◽  
S. V. Fazal ◽  
A. S. Lazar ◽  
R. A. Barker
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Transgenic Animal ◽  
Disease Stage ◽  
Disease Manifestation ◽  
Slow Progression ◽  
Transgenic Animal Models ◽  
Sleep Abnormalities ◽  
Early Disease Stage ◽  
Rare Opportunity

Abstract Introduction Mounting evidence supports the existence of an important feedforward cycle between sleep and neurodegeneration, wherein neurodegenerative diseases cause sleep and circadian abnormalities, which in turn exacerbate and accelerate neurodegeneration. If so, sleep therapies bear important potential to slow progression in these diseases. Findings This cycle is challenging to study, as its bidirectional nature renders cause difficult to disentangle from effect. Likewise, well-controlled intervention studies are often impractical in the setting of established neurodegenerative disease. It is this that makes understanding sleep and circadian abnormalities in Huntington’s disease (HD) important: as a monogenic fully penetrant neurodegenerative condition presenting in midlife, it provides a rare opportunity to study sleep and circadian abnormalities longitudinally, prior to and throughout disease manifestation, and in the absence of confounds rendered by age and comorbidities. It also provides potential to trial sleep therapies at a preclinical or early disease stage. Moreover, its monogenic nature facilitates the development of transgenic animal models through which to run parallel pre-clinical studies. HD, therefore, provides a key model condition through which to gain new insights into the sleep-neurodegeneration interface. Conclusions Here, we begin by summarising contemporary knowledge of sleep abnormalities in HD, and consider how well these parallel those of Alzheimer’s and Parkinson’s as more common neurodegenerative conditions. We then discuss what is currently known of the sleep-neurodegeneration cyclical relationship in HD. We conclude by outlining key directions of current and future investigation by which to advance the sleep-neurodegeneration field via studies in HD.

scholarly journals Transplantation of human embryonic stem cells alleviates motor dysfunction in AAV2-Htt171-82Q transfected rat model of Huntington’s disease

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jaisan Islam ◽  
Kyoung Ha So ◽  
Elina KC ◽  
Hyeong Cheol Moon ◽  
Aryun Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Human Embryonic Stem Cells ◽  
Rat Model ◽  
Sham Group ◽  
Embryonic Stem ◽  
Motor Dysfunction ◽  
Control Group

Abstract Background Human embryonic stem cells (hESCs) transplantation had shown to provide a potential source of cells in neurodegenerative disease studies and lead to behavioral recovery in lentivirus transfected or, toxin-induced Huntington's disease (HD) rodent model. Here, we aimed to observe if transplantation of superparamagnetic iron oxide nanoparticle (SPION)-labeled hESCs could migrate in the neural degenerated area and improve motor dysfunction in an AAV2-Htt171-82Q transfected Huntington rat model. Methods All animals were randomly allocated into three groups at first: HD group, sham group, and control group. After six weeks, the animals of the HD group and sham group were again divided into two subgroups depending on animals receiving either ipsilateral or contralateral hESCs transplantation. We performed cylinder test and stepping test every two weeks after AAV2-Htt171-82Q injection and hESCs transplantation. Stem cell tracking was performed once per two weeks using T2 and T2*-weighted images at 4.7 Tesla MRI. We also performed immunohistochemistry and immunofluorescence staining to detect the presence of hESCs markers, huntingtin protein aggregations, and iron in the striatum. Results After hESCs transplantation, the Htt virus-injected rats exhibited significant behavioral improvement in behavioral tests. SPION labeled hESCs showed migration with hypointense signal in MRI. The cells were positive with βIII-tubulin, GABA, and DARPP32. Conclusion Collectively, our results suggested that hESCs transplantation can be a potential treatment for motor dysfunction of Huntington's disease.

scholarly journals Significant Association Between Huntingtin Gene Mutation and Prevalence of Hopelessness, Depression and Anxiety Symptoms

2021 ◽  
Vol 28 (1) ◽  
pp. 4
Author(s):  
Adelė Butėnaitė ◽  
Robertas Strumila ◽  
Aistė Lengvenytė ◽  
Indrė Kotryna Pakutkaitė ◽  
Aušra Morkūnienė ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Gene Mutation ◽  
Psychiatric Symptoms ◽  
Depression Scale ◽  
Anxiety Symptoms ◽  
Motor Dysfunction ◽  
Cag Repeats ◽  
Control Group ◽  
P Value

Background: In Huntington’s disease psychiatric symptoms may manifest prior to motor dysfunction. Such symptoms negatively impact people’s quality of life and can worsen the course of the primary disease. The aim of the present study was to assess and compare depression, anxiety and hopelessness rates in individuals with and without an abnormal expansion of CAG repeats in the huntingtin (HTT) gene and healthy controls.Materials and methods: Study involved 31 individuals referred for genetic testing for Huntington’s disease and a control group of 41. Depressive and anxiety symptoms were assessed using Beck Hopelessness Scale (BHS) and Hospital Anxiety and Depression Scale (HADS). Results between groups were compared using the Mann–Whitney U test. Two-sided Bonferroni corrected p-value was set at ≤0.017.Results: Individuals with HTT gene mutation (“gene mutation positive”, GMP) (N=20) scored higher on the HADS depression subscale (5.90 ± 4.52 vs 1.36 ± 1.91; p ≤ 0.017) than those without HTT gene mutation (“gene mutation negative”, GMN) (N=11). GMP and control groups scored higher than the GMN group on the BHS (5.65 ± 3.91 vs 2.09 ± 1.64 and 5.27 ± 4.11 vs 2.09 ± 1.64, respectively; p ≤ 0.017). No differences in anxiety levels were found.Conclusions: Depressive symptoms and hopelessness were more prevalent in individuals with HTT gene mutation than in individuals who were tested but had no said mutation. Such results emphasise the importance of timely diagnosis and treatment of psychiatric comorbidities in individuals affected by Huntington’s disease.

scholarly journals Long-Term Efficacy and Safety of Deutetrabenazine for Chorea in Huntington’s Disease: Results From the ARC-HD Open-label Study

CNS Spectrums ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 164-165
Author(s):  
Samuel Frank ◽  
Claudia M. Testa ◽  
David Stamler ◽  
Elise Kayson ◽  
David Oakes ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rating Scale ◽  
Study Drug ◽  
Motor Dysfunction ◽  
Open Label ◽  
Entire Treatment Period ◽  
End Of Treatment ◽  
Pharmaceutical Industries

AbstractBackgroundChorea is a prominent motor dysfunction in Huntington’s disease (HD). Deutetrabenazine, a vesicular monoamine transporter 2 (VMAT2) inhibitor, is FDA-approved for the treatment of chorea in HD. In the pivotal, 12-week First-HD trial, deutetrabenazine treatment reduced the Unified Huntington’s Disease Rating Scale (UHDRS) total maximal chorea (TMC) score versus placebo. ARC-HD, an open-label extension study, evaluated long-term safety and efficacy of deutetrabenazine dosed in a response-driven manner for treatment of HD chorea.MethodsPatients who completed First-HD (Rollover) and patients who converted overnight from a stable dose of tetrabenazine (Switch) were included. Safety was assessed over the entire treatment period; exposure-adjusted incidence rates (EAIRs; adverse events [AEs] per person-year) were calculated. A stable, post-titration time point of 8 weeks was chosen for efficacy analyses.ResultsOf 119 patients enrolled (Rollover, n=82; Switch, n=37), 100 (84%) completed ≥1 year of treatment (mean [SD] follow-up, 119 [48] weeks). End of study EAIRs for patients in the Rollover and Switch cohorts, respectively, were: any AE, 2.6 and 4.3; serious AEs, 0.13 and 0.14; AEs leading to dose suspension, 0.05 and 0.04. Overall, 68% and 73% of patients in Rollover and Switch, respectively, experienced a study drug–related AE. Most common AEs possibly related to study drug were somnolence (17% Rollover; 27% Switch), depression (23%; 19%), anxiety (9%; 11%), insomnia (10%; 8%), and akathisia (9%; 14%). Rates of AEs of interest include suicidality (9%; 3%) and parkinsonism (6%; 11%). In both cohorts, mean UHDRS TMC score and total motor score (TMS) decreased from baseline to Week 8; mean (SD) change in TMC score (units) was –4.4 (3.1) and –2.1 (3.3) and change in TMS was –7.1 (7.3) and –2.4 (8.7) in Rollover and Switch, respectively. While receiving stable dosing from Week 8 to 132 (or end of treatment), patients showed minimal change in TMC score (0.9 [5.0]), but TMS increased compared to Week 8 (9.0 [11.3]). Upon drug withdrawal, there were no remarkable AEs and TMC scores increased 4.4 (3.7) units compared to end of treatment.ConclusionsThe type and severity of AEs observed in long-term deutetrabenazine exposure are consistent with the previous study. Efficacy in reducing chorea persisted over time. There was no unexpected worsening of HD or chorea associated with HD upon deutetrabenazine withdrawal.FundingTeva Pharmaceutical Industries Ltd., Petach Tikva, Israel

Colchicine in Behçet Syndrome: A Longterm Survey of Patients in a Controlled Trial

2014 ◽  
Vol 41 (4) ◽  
pp. 735-738 ◽  
Author(s):  
Vedat Hamuryudan ◽  
Gulen Hatemi ◽  
Koray Tascilar ◽  
Sebahattin Yurdakul ◽  
Cem Mat ◽  
...  
Keyword(s):  
Controlled Trial ◽  
Disease Stage ◽  
Early Disease ◽  
Double Blind ◽  
Behçet Syndrome ◽  
Behcet Syndrome ◽  
Cumulative Duration ◽  
Continuous Use ◽  
Early Disease Stage

Objective.To test the hypothesis that colchicine use during early disease decreases immunosuppressive use in Behçet syndrome (BS) in the long term.Methods.Patients with BS who participated in a double-blind, placebo-controlled trial of colchicine 16.6 ± 1.1 years ago were evaluated for immunosuppressive use during the posttrial period.Results.We could contact 90/116 patients; 28 (31%) received immunosuppressives during the posttrial period, 14 being from the colchicine arm. Posttrial colchicine use and cumulative duration were similar between patients who received immunosuppressives and those who did not.Conclusion.Continuous use of colchicine, even when initiated at an early disease stage, does not seem to decrease the use of immunosuppressives in the long term.

scholarly journals Early Motor Dysfunction and Striosomal Distribution of Huntingtin Microaggregates in Huntington's Disease Knock-In Mice

2002 ◽  
Vol 22 (18) ◽  
pp. 8266-8276 ◽  
Author(s):  
Liliana B. Menalled ◽  
Jessica D. Sison ◽  
Ying Wu ◽  
Melisa Olivieri ◽  
Xiao-Jiang Li ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Motor Dysfunction

scholarly journals The Utility of BDNF Detection in Assessing Severity of Huntington’s Disease

2021 ◽  
Vol 10 (21) ◽  
pp. 5181
Author(s):  
Klaudia Plinta ◽  
Andrzej Plewka ◽  
Krzysztof Pawlicki ◽  
Nikola Zmarzły ◽  
Magdalena Wójcik-Pędziwiatr ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Enzyme Linked Immunosorbent Assay ◽  
Functional Evaluation ◽  
Early Disease ◽  
Bdnf Level ◽  
Clinical Profiles ◽  
Clinical Pictures ◽  
Disease Stages ◽  
The Relationship

Brain-derived neurotrophic factor (BDNF) is involved in the survival and maturation of neurons, and also promotes and controls neurogenesis. Its levels are lowered in many neurodegenerative diseases, including Huntington’s disease (HD). Clinical pictures of HD can be very diverse, which makes it difficult to assess its severity; however, molecular markers may be helpful. The aim of the study was to determine the relationship between HD severity and the plasma BDNF concentration in HD patients. The study recruited 42 patients with diagnosed and genetically confirmed HD and 40 healthy volunteers. BDNF levels were determined in plasma with the enzyme-linked immunosorbent assay (ELISA). Correlations between BDNF levels and clinical profiles and HD severity were also investigated. The BDNF level was significantly lower in HD patients compared to the control. There was no correlation between the BDNF level and motor symptoms and cognitive impairment. In the early disease stages, BDNF levels were associated with a better neurological examination, independence, and functional evaluation, in contrast to later HD stages, where the correlations were inverse. Multidirectional correlations between parameters of saccadic disorders and the BDNF level do not allow for drawing a conclusion, whether or not there is a relationship between the severity of saccadic disorders and the BDNF concentration.

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