Long-term clinical and positron emission tomography outcome of fetal striatal transplantation in Huntington's disease

Reuter, Iris; Tai, Yen F.; Pavese, Nicola; Chaudhuri, K. Ray; Mason, Sarah; Polkey, Charles E.; Clough, C; Brooks, David J.; Barker, Roger A.; Piccini, Paola

doi:10.1136/jnnp.2007.142380

Cited by 112 publications

(82 citation statements)

References 11 publications

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“…Preliminary, open-label studies of neural transplants in patients with HD have demonstrated approximately 2 to 4 years of modest clinical benefits, followed by progressive clinical deterioration similar to the natural history of the disease (31,32), although there is 1 anecdotal case report of more meaningful clinical benefit (33). The safety profile for neural transplantation in HD may differ significantly from neural transplantation in Parkinson's disease (PD) (32,34).…”

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confidence: 99%

Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration

Cicchetti

Saporta

Hauser

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

176

182

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The clinical evaluation of neural transplantation as a potential treatment for Huntington's disease (HD) was initiated in an attempt to replace lost neurons and improve patient outcomes. Two of 3 patients with HD reported here, who underwent neural transplantation containing striatal anlagen in the striatum a decade earlier, have demonstrated marginal and transient clinical benefits. Their brains were evaluated immunohistochemically and with electron microscopy for markers of projection neurons and interneurons, inflammatory cells, abnormal huntingtin protein, and host-derived connectivity. Surviving grafts were identified bilaterally in 2 of the subjects and displayed classic striatal projection neurons and interneurons. Genetic markers of HD were not expressed within the graft. Here we report in patients with HD that (i) graft survival is attenuated long-term; (ii) grafts undergo disease-like neuronal degeneration with a preferential loss of projection neurons in comparison to interneurons; (iii) immunologically unrelated cells degenerate more rapidly than the patient's neurons, particularly the projection neuron subtype; (iv) graft survival is attenuated in the caudate in comparison to the putamen in HD; (v) glutamatergic cortical neurons project to transplanted striatal neurons; and (vi) microglial inflammatory changes in the grafts specifically target the neuronal components of the grafts. These results, when combined, raise uncertainty about this potential therapeutic approach for the treatment of HD. However, these observations provide new opportunities to investigate the underlying mechanisms involved in HD, as well as to explore additional therapeutic paradigms. excitotoxicity ͉ inflammation ͉ mutant huntingtin ͉ glutamate ͉ microglia

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mentioning

confidence: 99%

Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration

Cicchetti

Saporta

Hauser

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

176

182

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show abstract

“…Another pilot study assessing the usefulness of fetal cell grafts involving 2 patients with moderate HD was reported by Reuter et al [18]. The patients had identical huntingtin mutations (with 43 cystosine adenine guanine (CAG) repeats); one had been symptomatic for 6 years, and the other for 4 years.…”

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confidence: 99%

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

Benraiss

Goldman

2011

Neurotherapeutics

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“…11 In one patient the graft led to cyst formation and overgrowth 10 years posttransplantation and the patient died because of advanced HD. 12 In an exceptional case, Reuter et al 13 reported improvement in motor function and striatal PET scans over a period of 5 years in one of two patients who received bilateral foetal striatal tissue, and Capetian et al 14 reported in a post-mortem analysis of a single patient 6 months after transplantation, differentiation and integration of the transplanted tissue into the host tissue without improvement of movement or psychiatric symptoms.…”

Section: Cell Transplantation Provides An Improvement Of Symptoms Formentioning

confidence: 99%

Progress and prospects: stem cells and neurological diseases

2010

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Long-term clinical and positron emission tomography outcome of fetal striatal transplantation in Huntington's disease

Cited by 112 publications

References 11 publications

Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration

Neural transplants in patients with Huntington's disease undergo disease-like neuronal degeneration

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

Progress and prospects: stem cells and neurological diseases

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