Paucity of P-zones in striatal grafts prohibit commencement of clinical trials in Huntington's disease

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.

Download Full-text

Huntington’s Disease Clinical Trials Corner: June 2019

Journal of Huntington s Disease ◽

10.3233/jhd-199003 ◽

2019 ◽

Vol 8 (3) ◽

pp. 363-371 ◽

Cited By ~ 5

Author(s):

Filipe B. Rodrigues ◽

Joaquim J. Ferreira ◽

Edward J. Wild

Keyword(s):

Clinical Trials ◽

Huntington's Disease ◽

Huntington’S Disease

Download Full-text

Fifteen Years of Clinical Trials in Huntington’s Disease: A Very Low Clinical Drug Development Success Rate

Journal of Huntington s Disease ◽

10.3233/jhd-170245 ◽

2017 ◽

Vol 6 (2) ◽

pp. 157-163 ◽

Cited By ~ 30

Author(s):

André M. Travessa ◽

Filipe B. Rodrigues ◽

Tiago A. Mestre ◽

Joaquim J. Ferreira

Keyword(s):

Clinical Trials ◽

Drug Development ◽

Huntington's Disease ◽

Success Rate ◽

Huntington’S Disease ◽

Clinical Drug Development ◽

Clinical Drug

Download Full-text

Premanifest and Early Huntington’s Disease

10.1093/med/9780199929146.003.0005 ◽

2014 ◽

Cited By ~ 2

Author(s):

Edward J. Wild ◽

Sarah J. Tabrizi

Keyword(s):

Clinical Trials ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Clinical Setting ◽

Disease Onset ◽

Multidisciplinary Care ◽

Subjective Symptoms ◽

Hd Gene ◽

Stochastic Event ◽

Made In

The traditional view that individuals carrying an expanded Huntington’s disease (HD) gene undergo phenoconversion, a stochastic event that takes them from symptom-free to symptomatic, is now disputed among clinicians, HD researchers, and patient and family advocates. Disease onset is officially declared when neurologic abnormalities that are unequivocally due to HD are diagnosed, but subjective symptoms and objective signs emerge gradually, and it is more helpful to consider and openly discuss a prodromal period, often as long as 10 years, which can provide a helpful framework for discussion and management. Considerable progress has been made in defining the neurobiologic processes that underlie the development of HD in humans and measures that can predict this for the purpose of conducting clinical trials, but these measures have not yet been validated sufficiently to make them useful in the clinical setting. This chapter discusses the multidisciplinary care of patients with premanifest, prodromal, and early manifest HD.

Download Full-text

Huntington’s disease

Oxford Textbook of Neurologic and Neuropsychiatric Epidemiology ◽

10.1093/med/9780198749493.003.0010 ◽

2020 ◽

pp. 83-92

Author(s):

Juliana R Dutra ◽

Tanya P Garcia ◽

Karen Marder

Keyword(s):

Clinical Trials ◽

Huntington's Disease ◽

Huntington’S Disease ◽

Trinucleotide Repeat ◽

Neurodegenerative Disorder ◽

Genetic Mutation ◽

Current Standard ◽

Disease Modifying ◽

Disease Modifying Agents ◽

A Current

Huntington’s disease (HD) is an autosomal dominant, neurodegenerative disorder caused by an unstable expansion in the cytosine adenine guanine (CAG) trinucleotide repeat in the huntingtin gene. The disease onsets gradually over many years and its symptoms include extrapyramidal movement disorder, cognitive impairment, and behavioural changes. Understanding the overall progression of HD is critical to designing clinical trials with possible disease modifying agents. Research in this area has exploded in the past two decades, as different multicentre studies have evaluated both clinical and biological measures in individuals at different stages of the disease (i.e. at-risk for the genetic mutation, pre-manifest, and manifest HD). In this chapter, we provide readers with a current understanding of HD progression. This includes an overview of the current standard for how HD is clinically evaluated, descriptive epidemiology of the disease, genetics of HD, and a review of potential disease modifiers.

Download Full-text