F32 Exploring the feasibility of a novel and efficient trial design for the evaluation of long-term physical activity and exercise outcomes in people with huntington’s disease

2021 ◽  
Author(s):  
Monica Busse ◽  
Rebecca Playle ◽  
Cheney JG Drew ◽  
Katie Taiyari ◽  
Rhys Williams-Thomas ◽  
...  
Keyword(s):  
Physical Activity ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Trial Design ◽  
Physical Activity And Exercise

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

scholarly journals The development of PAT‐HD: A co‐designed tool to promote physical activity in people with Huntington’s disease

2021 ◽  
Vol 24 (2) ◽  
pp. 638-647
Author(s):  
Una Jones ◽  
Katy Hamana ◽  
Fran O’Hara ◽  
Monica Busse
Keyword(s):  
Physical Activity ◽  
Huntington's Disease ◽  
Huntington’S Disease

scholarly journals Direct assessment of presynaptic modulation of cortico-striatal glutamate release in a Huntington’s disease mouse model

2018 ◽  
Vol 120 (6) ◽  
pp. 3077-3084 ◽  
Author(s):  
Ellen T. Koch ◽  
Cameron L. Woodard ◽  
Lynn A. Raymond
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
High Frequency ◽  
Glutamate Release ◽  
Presynaptic Receptors ◽  
High Frequency Stimulation ◽  
Presynaptic Modulation ◽  
Frequency Stimulation

Glutamate is the main excitatory neurotransmitter in the brain, and impairments in its signaling are associated with many neurological disorders, including Huntington’s disease (HD). Previous studies in HD mouse models demonstrate altered glutamate receptor distribution and signaling at cortico-striatal synapses, and some studies suggest that glutamate release is altered; however, traditional methods to study synaptic glutamate release are indirect or have poor temporal resolution. Here we utilize iGluSnFR, a modified green fluorescent protein reporter for real-time imaging of glutamate transmission, to study presynaptic modulation of cortical glutamate release in the striatum of the YAC128 HD mouse model. We determined that iGluSnFR can be used to accurately measure short- and long-term changes in glutamate release caused by modulation of extracellular Ca2+ levels, activation of presynaptic receptors, and high-frequency stimulation (HFS) protocols. We also confirmed a difference in the expression of HFS-induced long-term depression in YAC128. Together, this research demonstrates the utility of iGluSnFR in studying presynaptic modulation of glutamate release in healthy mice and disease models that display impairments in glutamate signaling. NEW & NOTEWORTHY We use iGluSnFR to directly assess presynaptic modulation of cortico-striatal glutamate release in brain slice and compare changes in glutamate release between wild type and a Huntington’s disease mouse model, YAC128. We observed reductions in glutamate release after low extracellular Ca2+ and activation of various presynaptic receptors. We also demonstrate a presynaptic mechanism of reduced glutamate release in high-frequency stimulation-induced long-term depression and show this to be altered in YAC128.

K28 Experiences of patients with huntington’s disease on home cooked hot meals in a long term care facility

2016 ◽  
Vol 87 (Suppl 1) ◽  
pp. A88.3-A89
Author(s):  
Lia van Gelder ◽  
Femke Drost ◽  
Ria de Bruin ◽  
Jonieke Bredewold ◽  
Tineke Bredewold ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Long Term Care ◽  
Care Facility ◽  
Term Care ◽  
Term Care Facility ◽  
Long Term Care Facility

“She Is So Fidgety”

2016 ◽  
Author(s):  
Robertus M. A. de Bie ◽  
Susanne E. M. Ten Holter
Keyword(s):  
Physical Activity ◽  
Genetic Testing ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mental Activity ◽  
Adult Onset ◽  
Involuntary Movements ◽  
Writing Movements

Chorea manifests as involuntary, often contnuous, unpredictable, and involuntary dance-like movements. Patients with chorea are often unaware that they have involuntary movements. Others may try to incorporate the movement into a semipurposeful action (parakinesia). Chorea is usually worse with mental activity or emotion. Physical activity may also exacerbate chorea. The presence of “motor impersistence” is typical of chorea. Sometimes patients can also make unintentional sounds referred to as hyperkinetic dysarthria. Chorea disappears during sleep. Ballism is considered a type of chorea with a more proximal distribution and larger movements. Athetosis is a term formally used for chorea with slow writing movements in the distal limbs, but it is not considered a specific entity of chorea anymore. The most important genetic cause of chorea in adulthood is Huntington’s disease, and genetic testing should be considered as a first step in all patients with adult-onset chorea if no secondary cause is found.

Ethical aspects of a predictive test for Huntington’s Disease

2016 ◽  
Vol 23 (5) ◽  
pp. 565-575 ◽  
Author(s):  
Petra Lilja Andersson ◽  
Åsa Petersén ◽  
Caroline Graff ◽  
Anna-Karin Edberg
Keyword(s):  
Moral Responsibility ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Suicide Attempts ◽  
Genetic Test ◽  
Predictive Test ◽  
The Family ◽  
Long Term Consequences ◽  
Test Result

Background: A predictive genetic test for Huntington’s disease can be used before any symptoms are apparent, but there is only sparse knowledge about the long-term consequences of a positive test result. Such knowledge is important in order to gain a deeper understanding of families’ experiences. Objectives: The aim of the study was to describe a young couple’s long-term experiences and the consequences of a predictive test for Huntington’s disease. Research design: A descriptive case study design was used with a longitudinal narrative life history approach. Participants and research context: The study was based on 18 interviews with a young couple, covering a period of 2.5 years; starting 6 months after the disclosure of the test results showing the woman to be a carrier of the gene causing Huntington’s disease. Ethical considerations: Even though the study was extremely sensitive, where potential harm constantly had to be balanced against the benefits, the couple had a strong wish to contribute to increased knowledge about people in their situation. The study was approved by the ethics committee. Findings: The results show that the long-term consequences were devastating for the family. This 3-year period was characterized by anxiety, repeated suicide attempts, financial difficulties and eventually divorce. Discussion: By offering a predictive test, the healthcare system has an ethical and moral responsibility. Once the test result is disclosed, the individual and the family cannot live without the knowledge it brings. Support is needed in a long-term perspective and should involve counselling concerning the families’ everyday life involving important decision-making, reorientation towards a new outlook of the future and the meaning of life. Conclusion: As health professionals, our ethical and moral responsibility thus embraces not only the phase in direct connection to the actual genetic test but also a commitment to provide support to help the family deal with the long-term consequences of the test.

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