Motor and cognitive improvements in patients with Huntington's disease after neural transplantation

Bachoud‐Lévi, Anne‐Catherine; Rémy, Philippe; Nǵuyen, Jean-Paul; Brugières, Pierre; Lefaucheur, Jean‐Pascal; Bourdet, Catherine; Baudic, Sophie; Gaura, Véronique; Maison, Patrick; Haddad, Bassam; Boissé, Marie-Françoise; Grandmougin, Thierry; Jeny, R.; Bartolomeo, Paolo; Barba, Gianfranco Dalla; Degos, Jean‐Denis; Lisovoski, F.; Ergis, Anne-Marie; Pailhous, Edwige; Césaro, P.; Hantraye, Philippe; Peschanski, Marc

doi:10.1016/s0140-6736(00)03310-9

Cited by 412 publications

(248 citation statements)

References 25 publications

Supporting

Mentioning

232

Contrasting

Unclassified

Order By: Relevance

“…The transplantation of human fetal striatal tissue might serve as a useful therapeutic strategy and has led to encouraging results in clinical studies (Bachoud-Levi et al, 2000;Peschanski et al, 2004;Bachoud-Levi et al, 2006). However, adult stem cells such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs) represent an attractive alternative.…”

Section: Introductionmentioning

confidence: 99%

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

Bantubungi

Blum

Cuvelier

et al. 2008

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

Neural and mesenchymal stem cells have been proposed as alternative sources of cells for transplantation into the brain in neurodegenerative disorders. However, the endogenous factors controlling their engraftment within the injured parenchyma remain ill-defined. Here, we demonstrate significant engraftment of undifferentiated exogenous mesenchymal or neural stem cells throughout the lesioned area in a rat model for Huntington's disease, as late as 8 weeks post-transplantation. We show that stem cell factor (SCF), strongly up-regulated within host cells in the damaged striatum, is able to activate the SCF receptor c-kit and its signaling pathway and to promote the migration and proliferation of mesenchymal and neural stem cells in vitro. Furthermore, c-kit receptor blockade alters neural stem cell distribution within the lesioned striatum. Host SCF expression is observed in atypical cells expressing glial fibrillary acidic protein and doublecortin in the lesioned striatum and in migrating doublecortin-positive progenitors. Taken together, these data demonstrate that SCF produced in situ in the lesioned striatum is an important factor in promoting the engraftment of stem cells within the lesioned brain.

show abstract

Section: Introductionmentioning

confidence: 99%

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

Bantubungi

Blum

Cuvelier

et al. 2008

Molecular and Cellular Neuroscience

View full text Add to dashboard Cite

show abstract

“…Each graft was comprised of a single ganglionic eminence, dissected from 7.5-to 9.5-week-old human fetal brains. Positron-emission tomographic (PET) measurement of (18F)-fluorodeoxyglucose uptake revealed sustained metabolic activity following engraftment (EPs), whereas the median nerve somatosensory evoked potentials of transplant recipients exhibited less degradation of cortical EPs than did those of 22 untreated patients [10]. Serial PET imaging confirmed that cortical metabolism in 3 patients improved during the 2-year follow-up, concurrent with clinical stabilization, suggesting functional integration of the grafts [11].…”

mentioning

confidence: 99%

“…Another trial was reported 2 years later by Bachoud-Levi et al [10], in which 5 HD patients received temporally staggered bilateral intrastriatal grafts, with a 1-year interval between the 2 procedures. Each graft was comprised of a single ganglionic eminence, dissected from 7.5-to 9.5-week-old human fetal brains.…”

mentioning

confidence: 99%

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

Benraiss

Goldman

2011

Neurotherapeutics

View full text Add to dashboard Cite

“…Their performance was compared with a cohort of 20 patients with HD who did not undergo fetal cell transplant. 111 At 1 year after the second surgery, fluorodeoxyglucose positron emission tomography (FDG-PET) showed an increase or stability in metabolism, suggesting metabolically active neural grafts in three of the five patients with transplants, compared with the annual 7% loss in striatal metabolic activity recorded in the control group. The same three patients maintained several neuropsychological results in the normal range, improved their activities of independent living, had a slower decline rate of the UHDRS (chorea and bradykinesia) scores, compared with the HD control cohort, but lost 1 point on the TFC scale.…”

Section: Fetal Cell Transplantationmentioning

confidence: 99%

“…The procedure seems safe, although risks exist, and these initial results are modest but promising-although much can be learned from the Parkinson's disease experience with doubleblind sham surgeries. The poor compliance of HD patients with the immunotherapy in one of the studies, 111 and the lack of pathological evidence of graft rejection by the host tissue on autopsy, make the utility of immunosuppressive therapy debatable.…”

Section: Fetal Cell Transplantationmentioning

confidence: 99%

Symptomatic Treatment of Huntington Disease

2008

View full text Add to dashboard Cite

Summary: Huntington disease (HD) is a progressive heredoneurodegenerative disease manifested by chorea and other hyperkinetic (dystonia, myoclonus, tics) and hypokinetic (parkinsonism) movement disorders. In addition, a variety of psychiatric and behavioral symptoms, along with cognitive decline, contribute significantly to the patient's disability. Because there are no effective neuroprotective therapies that delay the progression of the disease, symptomatic treatment remains the cornerstone of medical management. Several classes of medications have been used to ameliorate the various symptoms of HD, including typical and atypical neuroleptics, dopamine depleters, antidepressants, antiglutamatergic drugs, GABA agonists, antiepileptic medications, acetylcholinesterase inhibitors, and botulinum toxin. Recently, surgical approaches including pallidotomy, deep brain stimulation, and fetal cell transplants have been used for the symptomatic treatment of HD. The selected therapy must be customized to the needs of each patient, minimizing the potential adverse effects. The primary aim of this article is to review the role of the different therapies, both available and investigational, for the treatment of the motor, psychiatric, behavioral, and cognitive symptoms of HD, and to examine their impact on the patient's functionality and quality of life.

show abstract

Motor and cognitive improvements in patients with Huntington's disease after neural transplantation

Cited by 412 publications

References 25 publications

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

Stem cell factor and mesenchymal and neural stem cell transplantation in a rat model of Huntington's disease

Cellular Therapy and Induced Neuronal Replacement for Huntington's Disease

Symptomatic Treatment of Huntington Disease

Contact Info

Product

Resources

About