Rationale for intrastriatal grafting of striatal neuroblasts in patients with Huntington's disease. 1995

M Peschanski, and P Cesaro, and P Hantraye
INSERM U 421, IM3, Neuroplasticité et Thérapeutique, Faculté de Médecine, Créteil, France.

Huntington's disease is a genetic disease, autosomal and dominant, that induces motor disorders, an inexorable deterioration of higher brain functions and psychiatric disturbances. At present, there are no known therapeutics against Huntington's disease. The Network of European CNS Transplantation and Restoration (NECTAR) has begun a program aimed at defining the conditions under which intrastriatal transplantation of fetal striatal cells could be attempted as an experimental treatment for Huntington's disease. This review presents the reasons why our group is considering participating in these trials. The validity of this therapeutic approach is supported by three main series of data: (i) neuropathological, clinical and imaging data indicate that Huntington's disease is, above all, a localized affection of a specific neuronal population ("medium-spiny" neurons) in the striatum; (ii) a large body of experimental results, obtained in rats and non-human primates, demonstrates that transplanted fetal striatal cells are able to integrate the host brain and to substitute for previously lesioned host striatal neurons; (iii) expertise in clinical neural transplantation has now been acquired from the treatment of patients with Parkinson's disease. These different sets of data are presented and discussed in this review. There are a number of problems which do not yet appear to be entirely resolved, nor are they likely to be using the experimental models currently available. These problems are identified and explicitly presented as working hypotheses. (1) Anatomo-functional results obtained in rodents and non-human primates with excitotoxic striatal lesions can serve as a basis for the extrapolation of what can be obtained from patients with Huntington's disease. (2). Huntington's disease can be efficiently fought by substituting degenerated striatal neurons alone. (3) Huntington's disease is due to a genetic defect which either hits the neurons that carry it directly or hits them indirectly only after several decades. Transplanted neurons, because they do not carry the gene or because they are of fetal origin, will not be rapidly affected by the ongoing disease process. Given the current state of knowledge, intracerebral transplantation appears to be the most serious opportunity (if not the only one that has been experimentally validated) for clinical improvement to be obtained in patients with Huntington's disease. The purpose of this review is to open a scientific discussion on its experimental bases before actual clinical trials start.

UI MeSH Term Description Entries
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006816 Huntington Disease A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4) Huntington Chorea,Juvenile Huntington Disease,Akinetic-Rigid Variant of Huntington Disease,Chorea, Chronic Progressive Hereditary (Huntington),Chronic Progressive Hereditary Chorea (Huntington),Huntington Chronic Progressive Hereditary Chorea,Huntington Disease, Akinetic-Rigid Variant,Huntington Disease, Juvenile,Huntington Disease, Juvenile-Onset,Huntington Disease, Late Onset,Huntington's Chorea,Huntington's Disease,Juvenile-Onset Huntington Disease,Late-Onset Huntington Disease,Progressive Chorea, Chronic Hereditary (Huntington),Progressive Chorea, Hereditary, Chronic (Huntington),Akinetic Rigid Variant of Huntington Disease,Chorea, Huntington,Chorea, Huntington's,Huntington Disease, Akinetic Rigid Variant,Huntington Disease, Juvenile Onset,Huntington Disease, Late-Onset,Juvenile Onset Huntington Disease,Late Onset Huntington Disease
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D017072 Neostriatum The phylogenetically newer part of the CORPUS STRIATUM consisting of the CAUDATE NUCLEUS and PUTAMEN. It is often called simply the striatum.
D017690 Cell Transplantation Transference of cells within an individual, between individuals of the same species, or between individuals of different species. Transplantation, Cell
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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