Cell-based technologies for Huntington's disease

Haddad, Mônica Santoro; Wenceslau, Cristiane Valverde; Pompéia, Celine; Kerkis, Irina

doi:10.1590/s1980-5764-2016dn1004006

Cited by 8 publications

(7 citation statements)

References 91 publications

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“…They are self-renewing, can release neuroprotective factors like BDNF and can differentiate into multiple cell types, potentially including neural cells. 217,218 No teratomas or overgrowths have been found in MSC animal model studies. 217 Striatal injection of mice UC-derived MSCs in R6/2 HD mice improved spatial memory and reduced neuropathological deficits, but did not change motor impairments.…”

Section: Stem Cell Therapiesmentioning

confidence: 99%

Current and Possible Future Therapeutic Options for Huntington’s Disease

Ferguson

Kennedy

Palpagama

et al. 2022

J Cent Nerv Syst Dis

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Huntington’s disease (HD) is an autosomal neurodegenerative disease that is characterized by an excessive number of CAG trinucleotide repeats within the huntingtin gene ( HTT). HD patients can present with a variety of symptoms including chorea, behavioural and psychiatric abnormalities and cognitive decline. Each patient has a unique combination of symptoms, and although these can be managed using a range of medications and non-drug treatments there is currently no cure for the disease. Current therapies prescribed for HD can be categorized by the symptom they treat. These categories include chorea medication, antipsychotic medication, antidepressants, mood stabilizing medication as well as non-drug therapies. Fortunately, there are also many new HD therapeutics currently undergoing clinical trials that target the disease at its origin; lowering the levels of mutant huntingtin protein (mHTT). Currently, much attention is being directed to antisense oligonucleotide (ASO) therapies, which bind to pre-RNA or mRNA and can alter protein expression via RNA degradation, blocking translation or splice modulation. Other potential therapies in clinical development include RNA interference (RNAi) therapies, RNA targeting small molecule therapies, stem cell therapies, antibody therapies, non-RNA targeting small molecule therapies and neuroinflammation targeted therapies. Potential therapies in pre-clinical development include Zinc-Finger Protein (ZFP) therapies, transcription activator-like effector nuclease (TALEN) therapies and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated system (Cas) therapies. This comprehensive review aims to discuss the efficacy of current HD treatments and explore the clinical trial progress of emerging potential HD therapeutics.

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Section: Stem Cell Therapiesmentioning

confidence: 99%

Current and Possible Future Therapeutic Options for Huntington’s Disease

Ferguson

Kennedy

Palpagama

et al. 2022

J Cent Nerv Syst Dis

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“…Huntington's disease (HD, OMIM #143100) is an autosomal dominant progressive and incurable neurodegenerative disease caused by an increase of CAG repeats of the huntingtin gene ( HTT locus 4p16.3), which leads to the progressive death of medium spiny neurons in the striatum [ 1 ]. The main goal of cell-based therapies is to repair the mechanisms underlying disease initiation and progression through the trophic effect [ 2 ]. Different cell types can be used for this purpose.…”

Section: Introductionmentioning

confidence: 99%

Human Immature Dental Pulp Stem Cells Did Not Graft into a Preexisting Human Lung Adenocarcinoma

Silva¹,

Araldi

Colozza‐Gama

et al. 2022

Case Rep Oncol

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Mesenchymal stem cell (MSC)-based therapies have been considered an attractive approach for treating Huntington’s disease (HD). However, due to the pulmonary first-passage effect associated with intravenous infusion (the most commonly used route of MSC administration), there is a rising concern that the cells could be entrapped in the lungs and grafted (homing) into preexisting lung cancer. Herein, we report the case of a patient with HD enrolled in a cell therapy phase I clinical trial for HD treatment having a preexisting pulmonary nodule. The nodule was found at the trial screening. The patient was referred to a pulmonologist who considered the nodule non-cancer and authorized enrollment. The patient received four intravenous administrations of human immature dental pulp stem cells (hIDPSCs) at the dose of 1 × 10<sup>6</sup> cells/kg of body weight within 2 years. One month after the last dose, a computerized tomography scan showed nodule growth. A bronchoscopy biopsy showed primary lung adenocarcinoma. The neoplasm was surgically excised (lung superior right lobectomy). The patient is cured of the neoplasm. The tumor was sectioned into six fragments, which were subjected to RNA-seq. The transcriptome of each tumor section was compared with the transcriptome of infused hIDPSCs using two statistical approaches: principal component analysis and NOIseq. Both results demonstrated a linear distance between the hIDPSCs and the lung adenocarcinoma. These results suggest that the infused hIDPSCs neither home nor graft within the pulmonary nodule.

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“…Existing therapeutic approaches are only able to alleviate symptoms, and therapies that slow or reverse disease progression have yet to be implemented. Preliminary clinical trials using fetal neural grafts have shown long-lasting functional benefits; however, these grafts were efficient only in limited cases [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

Csöbönyeiová

Polák

Danišovič

2020

IJMS

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Huntington’s disease (HD) is an inherited, autosomal dominant, degenerative disease characterized by involuntary movements, cognitive decline, and behavioral impairment ending in death. HD is caused by an expansion in the number of CAG repeats in the huntingtin gene on chromosome 4. To date, no effective therapy for preventing the onset or progression of the disease has been found, and many symptoms do not respond to pharmacologic treatment. However, recent results of pre-clinical trials suggest a beneficial effect of stem-cell-based therapy. Induced pluripotent stem cells (iPSCs) represent an unlimited cell source and are the most suitable among the various types of autologous stem cells due to their patient specificity and ability to differentiate into a variety of cell types both in vitro and in vivo. Furthermore, the cultivation of iPSC-derived neural cells offers the possibility of studying the etiopathology of neurodegenerative diseases, such as HD. Moreover, differentiated neural cells can organize into three-dimensional (3D) organoids, mimicking the complex architecture of the brain. In this article, we present a comprehensive review of recent HD models, the methods for differentiating HD–iPSCs into the desired neural cell types, and the progress in gene editing techniques leading toward stem-cell-based therapy.

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Cell-based technologies for Huntington's disease

Cited by 8 publications

References 91 publications

Current and Possible Future Therapeutic Options for Huntington’s Disease

Current and Possible Future Therapeutic Options for Huntington’s Disease

Human Immature Dental Pulp Stem Cells Did Not Graft into a Preexisting Human Lung Adenocarcinoma

Recent Overview of the Use of iPSCs Huntington’s Disease Modeling and Therapy

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