Neural Transplantation for the Treatment of Huntington’s Disease

2010 ◽  
Vol 5 (2) ◽  
pp. 41
Author(s):  
Roger A Barker ◽  
Rachel A Swain ◽  
◽  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neural Transplantation ◽  
Rodent Models ◽  
Complete Knowledge ◽  
Grafting Technique ◽  
Optimal Protocol ◽  
The Future ◽  
Successes And Failures

Neural transplantation studies where foetal striatal tissue is grafted into the striatum of patients with Huntington’s disease have taken place at several sites worldwide in recent years, following success in rodent models of the disease. Studies have for the most part been safe but have had various degrees of effectiveness. This article looks at the successes and failures of these studies and considers what has been learnt in terms of safety, techniques and methodology. While knowledge of the optimal protocol is advancing, there are still many aspects that need refining, such as immunosuppression and grafting technique. Although advances in this field are hampered by the need for more complete knowledge of the disease itself, the future of neural transplantation has a great deal of potential.

Huntington’s Disease and Neural Transplantation

1996 ◽  
pp. 445-454
Author(s):  
R. L. M. Faull ◽  
H. J. Waldvogel ◽  
L. F. B. Nicholson ◽  
M. N. Williams ◽  
M. Dragunow
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neural Transplantation

Neural Transplantation for Huntington's Disease: Experimental Rationale and Recommendations for Clinical Trials

1996 ◽  
Vol 5 (2) ◽  
pp. 339-352 ◽  
Author(s):  
Kathleen M. Shannon ◽  
Jeffrey H. Kordower
Keyword(s):  
Clinical Trials ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Treatment Strategies ◽  
Neural Transplantation ◽  
Trophic Factors ◽  
Trophic Factor ◽  
Striatal Neurons ◽  
Variable Parameters

Huntington's disease (HD) is a neurodegenerative disorder affecting motor function, personality, and cognition. This paper reviews the experimental data that demonstrate the potential for transplantation of fetal striatum and trophic factor secreting cells to serve as innovative treatment strategies for HD. Transplantation strategies have been effective in replacing lost neurons or preventing the degeneration of neurons destined to die in both rodent and nonhuman primate models of HD. In this regard, a logical series of investigations has proven that grafts of fetal striatum survive, reinnervate the host, and restore function impaired following excitotoxic lesions of the striatum. Furthermore, transplants of cells genetically modified to secrete trophic factors such as nerve growth factor protect striatal neurons from degeneration due to excitotoxicity or mitochondrial dysfunction. Given the disabling and progressive nature of HD, coupled with the absence of any meaningful medical therapy, it is reasonable to consider clinical trials of neural transplantation for this disease. Fetal striatal implants will most likely be the first transplant strategy attempted for HD. This paper describes the variable parameters we believe to be critical for consideration for the design of clinical trials using fetal striatal implants for the treatment of HD.

scholarly journals Large Animal Models of Huntington’s Disease: What We Have Learned and Where We Need to Go Next

2020 ◽  
Vol 9 (3) ◽  
pp. 201-216
Author(s):  
David Howland ◽  
Zdenka Ellederova ◽  
Neil Aronin ◽  
Deborah Fernau ◽  
Jill Gallagher ◽  
...  
Keyword(s):  
Animal Models ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Single Species ◽  
Research Community ◽  
Response To Treatment ◽  
Large Animal ◽  
Rodent Models ◽  
Large Animal Models ◽  
Translational Studies

Genetically modified rodent models of Huntington’s disease (HD) have been especially valuable to our understanding of HD pathology and the mechanisms by which the mutant HTT gene alters physiology. However, due to inherent differences in genetics, neuroanatomy, neurocircuitry and neurophysiology, animal models do not always faithfully or fully recapitulate human disease features or adequately predict a clinical response to treatment. Therefore, conducting translational studies of candidate HD therapeutics only in a single species (i.e. mouse disease models) may not be sufficient. Large animal models of HD have been shown to be valuable to the HD research community and the expectation is that the need for translational studies that span rodent and large animal models will grow. Here, we review the large animal models of HD that have been created to date, with specific commentary on differences between the models, the strengths and disadvantages of each, and how we can advance useful models to study disease pathophysiology, biomarker development and evaluation of promising therapeutics.

Hypothalamic Alterations in Huntington's Disease Patients: Comparison with Genetic Rodent Models

2014 ◽  
Vol 26 (11) ◽  
pp. 761-775 ◽  
Author(s):  
D. J. van Wamelen ◽  
N. A. Aziz ◽  
R. A. C. Roos ◽  
D. F. Swaab
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Rodent Models

scholarly journals Striatal Circuit Development and Its Alterations in Huntington’s Disease

2020 ◽  
Author(s):  
Margaux Lebouc ◽  
Quentin Richard ◽  
Maurice Garret ◽  
Jérôme Baufreton
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mouse Models ◽  
Neurodegenerative Disorder ◽  
Repeat Expansion ◽  
Cag Repeat ◽  
Rodent Models ◽  
Network Development ◽  
Cag Repeat Expansion ◽  
Circuit Development

Huntington's disease (HD) is an inherited neurodegenerative disorder that usually starts during midlife with progressive alterations of motor and cognitive functions. The disease is caused by a CAG repeat expansion within the huntingtin gene leading to severe striatal neurodegeneration. Recent studies conducted on pre-HD children highlight early striatal developmental alterations starting as soon as 6 years old, the earliest age assessed. These findings, in line with data from mouse models of HD, raise the question of when during development do the first disease-related striatal alterations emerge or whether they contribute to the later appearance of the neurodegenerative features of the disease. In this review we will describe the different stages of striatal network development and then discuss recent evidence for its alterations in rodent models of the disease. We argue that a better understanding of the striatum’s development should help in assessing aberrant neurodevelopmental processes linked to the HD mutation.

scholarly journals Confirming a Drosophila Melanogaster Model of Huntingtin Aggregation

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 1036-1037
Author(s):  
Akosua Biritwum ◽  
Simon Levy ◽  
Bess Frost ◽  
Atanu Duttaroy
Keyword(s):  
At Risk ◽  
Drosophila Melanogaster ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Mental State ◽  
Research Study ◽  
Autosomal Dominant ◽  
Robust Approach ◽  
The Future ◽  
Experimental Process

Abstract For decades, doctors, psychologists, and psychiatrists alike have struggled to treat the symptomatic effects of Huntington’s disease. Huntington’s disease is an autosomal dominant brain disease that results in the deterioration of a person’s physical and mental state. Once a person inherits the disease, they end up dying from it more often than not. At present, there are 41,000 Americans with symptomatic Huntington’s disease, and 200,000 more are currently at-risk of inheriting the disease. Given its 50/50 chance of inheritance, there seems to be no end in sight to this degenerative ailment. My research study, however, will show that with a more robust approach, finding a cure for this disease is possible. Ultimately, the aim of this project was to test an already established model in Drosophila melanogaster regarding the “huntingtin” protein responsible for Huntington’s disease. This was achieved by first demonstrating that the flies which were modified to produce huntingtin could, in fact, produce the protein. Secondly, an experimental process was created to configure a system through which the amount of protein produced by each fly could be quantified. This quantification was vital in creating a baseline that would allow for the identification of potential therapeutic treatments in the future. In short, by establishing a quantifiable model for huntingtin, this study will pave the way to new insights on huntingtin aggregation and the identification of possible treatments for Huntington’s disease in the future.

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