Cell Replacement Therapy for Huntington’s Disease

2020 ◽  
pp. 57-69
Author(s):  
Ruth Monk ◽  
Bronwen Connor
Keyword(s):  
Huntington's Disease ◽  
Replacement Therapy ◽  
Huntington’S Disease ◽  
Cell Replacement Therapy ◽  
Cell Replacement

Medium spiny neurons for transplantation in Huntington's disease

2009 ◽  
Vol 37 (1) ◽  
pp. 323-328 ◽  
Author(s):  
Claire M. Kelly ◽  
Stephen B. Dunnett ◽  
Anne E. Rosser
Keyword(s):  
Huntington's Disease ◽  
Replacement Therapy ◽  
Huntington’S Disease ◽  
Ethical Issues ◽  
Medium Spiny Neuron ◽  
Cell Replacement Therapy ◽  
Potential Donor ◽  
Cell Replacement ◽  
And Function

Cell-replacement therapy for Huntington's disease is one of very few therapies that has reported positive outcomes in clinical trials. However, for cell transplantation to be made more readily available, logistical, standardization and ethical issues associated with the current methodology need to be resolved. To achieve these goals, it is imperative that an alternative cell source be identified. One of the key requirements of the cells is that they are capable of acquiring an MSN (medium spiny neuron) morphology, express MSN markers such as DARPP-32 (dopamine- and cAMP-regulated phosphoprotein of 32 kDa), and function in vivo in a manner that replicates those that have been lost to the disease. Developmental biology has progressed in recent years to provide a vast array of information with regard to the key signalling events involved in the proliferation, specification and differentiation of striatal-specific neurons. In the present paper, we review the rationale for cell-replacement therapy in Huntington's disease, discuss some potential donor sources and consider the value of developmental markers in the identification of cells with the potential to develop an MSN phenotype.

scholarly journals Neural stem cells for cell replacement therapy for Huntington's disease

2006 ◽  
Vol 198 (2) ◽  
pp. 573-574 ◽  
Author(s):  
C.M. Kelly ◽  
A. Battersby ◽  
S.V. Precious ◽  
N.D. Allen ◽  
S.B. Dunnett ◽  
...  
Keyword(s):  
Stem Cells ◽  
Neural Stem Cells ◽  
Huntington's Disease ◽  
Replacement Therapy ◽  
Huntington’S Disease ◽  
Cell Replacement Therapy ◽  
Cell Replacement

scholarly journals Is there a place for human fetal-derived stem cells for cell replacement therapy in Huntington's disease?

2017 ◽  
Vol 106 ◽  
pp. 114-121 ◽  
Author(s):  
Sophie V. Precious ◽  
Rike Zietlow ◽  
Stephen B. Dunnett ◽  
Claire M. Kelly ◽  
Anne E. Rosser
Keyword(s):  
Stem Cells ◽  
Huntington's Disease ◽  
Replacement Therapy ◽  
Huntington’S Disease ◽  
Cell Replacement Therapy ◽  
Cell Replacement

scholarly journals Protocol for an open label: phase I trial within a cohort of foetal cell transplants in people with Huntington’s disease

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Cheney J G Drew ◽  
Feras Sharouf ◽  
Elizabeth Randell ◽  
Lucy Brookes-Howell ◽  
Kim Smallman ◽  
...  
Keyword(s):  
Phase I ◽  
Huntington's Disease ◽  
Replacement Therapy ◽  
Huntington’S Disease ◽  
Phase I Trial ◽  
Novel Therapies ◽  
Cell Replacement Therapy ◽  
Cell Replacement ◽  
Cell Transplants ◽  
Foetal Cell

Abstract Huntington’s disease is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington’s disease is characterized by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell-replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration is a phase I Trial Within a Cohort designed to assess safety and feasibility of transplanting human foetal striatal cells into the striatum of people with Huntington’s disease. A minimum of 18 participants will be enrolled in the study cohort, and up to five eligible participants will be randomly selected to undergo transplantation of 12–22 million foetal cells in a dose escalation paradigm. Independent reviewers will assess safety outcomes (lack of significant infection, bleeding or new neurological deficit) 4 weeks after surgery, and ongoing safety will be established before conducting each subsequent surgery. All participants will undergo detailed clinical and functional assessment at baseline (6 and 12 months). Surgery will be performed 1 month after baseline, and transplant participants will undergo regular clinical follow-up for at least 12 months. Evaluation of trial processes will also be undertaken. Transplant participants and their carers will be interviewed ∼1 month before and after surgery. Interviews will also be conducted with non-transplanted participants and healthcare staff delivering the intervention and involved in the clinical care of participants. Evaluation of clinical and functional efficacy outcomes and intervention costs will be carried out to explore plausible trial designs for subsequent randomized controlled trials aimed at evaluating efficacy and cost-effectiveness of cell-replacement therapy. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration will enable the assessment of the safety, feasibility, acceptability and cost of foetal cell transplants in people with Huntington’s disease. The data collected will inform trial designs for complex intra-cranial interventions in a range of neurodegenerative conditions and facilitate the development of stable surgical pipelines for delivery of future stem cell trials. Trial Registration: ISRCTN52651778

A microfluidic platform enables comprehensive gene expression profiling of mouse retinal stem cells

Lab on a Chip ◽  
2021 ◽  
Author(s):  
Shana O Kelley ◽  
Mahmoud Labib ◽  
Brenda Coles ◽  
Mahla Poudineh ◽  
Brendan Innes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Stem Cell ◽  
Visual Impairment ◽  
Gene Expression Profiling ◽  
Replacement Therapy ◽  
Retinal Degeneration ◽  
Expression Profiling ◽  
Cell Replacement Therapy ◽  
Cell Replacement

Loss of photoreceptors due to retinal degeneration is a major cause of untreatable visual impairment and blindness. Cell replacement therapy, using retinal stem cell (RSC)-derived photoreceptors, holds promise for reconstituting...

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