scholarly journals Patient-Specific iPSC-Based Models of Huntington’s Disease as a Tool to Study Store-Operated Calcium Entry Drug Targeting

2018 ◽  
Vol 9 ◽  
Author(s):  
Vladimir Vigont ◽  
Evgeny Nekrasov ◽  
Alexey Shalygin ◽  
Konstantin Gusev ◽  
Sergey Klushnikov ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Drug Targeting ◽  
Calcium Entry ◽  
Patient Specific ◽  
Store Operated Calcium Entry

scholarly journals Enhanced Store-Operated Calcium Entry Leads to Striatal Synaptic Loss in a Huntington's Disease Mouse Model

2016 ◽  
Vol 36 (1) ◽  
pp. 125-141 ◽  
Author(s):  
J. Wu ◽  
D. A. Ryskamp ◽  
X. Liang ◽  
P. Egorova ◽  
O. Zakharova ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Calcium Entry ◽  
Synaptic Loss ◽  
Store Operated Calcium Entry

scholarly journals Drug targeting of dysregulated transcription in Huntington's disease

2007 ◽  
Vol 83 (4) ◽  
pp. 249-259 ◽  
Author(s):  
Aleksey G. Kazantsev ◽  
Steven M. Hersch
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Drug Targeting

Improving Patient Outreach by Defining Telehealth Suitability in a Tertiary Huntington’s Disease Clinic

2021 ◽  
pp. 1-6
Author(s):  
Sean J. Lee ◽  
Lisa M. Hale ◽  
Elizabeth Huitz ◽  
Daniel O. Claassen ◽  
Katherine E. McDonell
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Screening Tool ◽  
Selection Process ◽  
Clinical Care ◽  
Patient Specific ◽  
Patient Centeredness ◽  
Remote Healthcare ◽  
Specific Factors ◽  
Patient Outreach

Background: The COVID-19 pandemic has increased the need for remote healthcare options among patients with Huntington’s disease (HD). However, since not every HD patient is suitable for telehealth, it is important to differentiate who can be seen virtually from who should remain as in-person. Unfortunately, there are no clinical guidelines on how to evaluate HD patients for telehealth eligibility. Objective: To standardize the teleneurology selection process in HD by implementing a screening tool that accounts for patient-specific factors. Methods: We organized various indications and contraindications to teleneurology into a flowchart. If any indications or contraindications were met, patients were assigned to telehealth or maintained as in-person, respectively. If no indications or contraindications were met, patients were given the option of telehealth or in-person for their upcoming appointments. In two implementation cycles, we tested this screening tool among all HD patients scheduled for clinic visits, aided by chart review and phone interview. Results: In a cohort of 81 patients, telehealth acceptance among eligible patients increased from 45.0%to 83.3%. Frequency of telehealth visits increased from a pre-intervention baseline of 12.8%to 28.2%. Conclusion: Teleneurology utilization among HD patients more than doubled across our study. Our intervention promotes consistency and patient-centeredness in HD clinical care and streamlines the overall telehealth selection process. Future studies can seek to reduce telehealth no-shows and also evaluate the utility of the motor and psychiatric criteria included in our screening tool.

scholarly journals STIM2 Mediates Excessive Store-Operated Calcium Entry in Patient-Specific iPSC-Derived Neurons Modeling a Juvenile Form of Huntington's Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Vladimir A. Vigont ◽  
Dmitriy A. Grekhnev ◽  
Olga S. Lebedeva ◽  
Konstantin O. Gusev ◽  
Egor A. Volovikov ◽  
...  
Keyword(s):  
Calcium Channels ◽  
Huntington's Disease ◽  
Calcium Signaling ◽  
Huntington’S Disease ◽  
Calcium Uptake ◽  
Neurodegenerative Disorder ◽  
Neuroprotective Effect ◽  
Induced Pluripotent Stem Cell ◽  
Patient Specific ◽  
Juvenile Form

Huntington's disease (HD) is a severe autosomal-dominant neurodegenerative disorder caused by a mutation within a gene, encoding huntingtin protein. Here we have used the induced pluripotent stem cell technology to produce patient-specific terminally differentiated GABA-ergic medium spiny neurons modeling a juvenile form of HD (HD76). We have shown that calcium signaling is dramatically disturbed in HD76 neurons, specifically demonstrating higher levels of store-operated and voltage-gated calcium uptakes. However, comparing the HD76 neurons with the previously described low-repeat HD models, we have demonstrated that the severity of calcium signaling alterations does not depend on the length of the polyglutamine tract of the mutant huntingtin. Here we have also observed greater expression of huntingtin and an activator of store-operated calcium channels STIM2 in HD76 neurons. Since shRNA-mediated suppression of STIM2 decreased store-operated calcium uptake, we have speculated that high expression of STIM2 underlies the excessive entry through store-operated calcium channels in HD pathology. Moreover, a previously described potential anti-HD drug EVP4593 has been found to attenuate high levels of both huntingtin and STIM2 that may contribute to its neuroprotective effect. Our results are fully supportive in favor of the crucial role of calcium signaling deregulation in the HD pathogenesis and indicate that the cornerstone of excessive calcium uptake in HD-specific neurons is a calcium sensor and store-operated calcium channels activator STIM2, which should become a molecular target for medical treatment and novel neuroprotective drug development.

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