COLD SPRING HARBOR, N.Y. -- While Congress and the presidentsparred last month over the use of human fetal tissue to treatParkinson's disease, two teams of neuro-genetic engineersreported successful tests of recombinant-DNA alternativetherapies.

They recently described their separate experiments in ratmodels to a Gene Therapy meeting here at the Cold SpringHarbor Laboratory.

Both approaches aim to implant genetically transduced cellsdeep in the human mid-brain, and incite its basal ganglia toproduce more of the neurotransmitter dopamine -- lack ofwhich brings on Parkinsonian symptoms.

-- Neurobiologist Lee A. Cunningham of the University ofRochester (N.Y.) School of Medicine and Dentistry told heraudience here that "if genetically engineered astrocytes candeliver human gene products to the brain to treat neurologicaldiseases such as Parkinson's, there would probably be no needto use fetal cells."

She and her associates began -- in rats -- by taking chromaffincells, which produce dopamine, from the medulla of the adrenalgland. To turn these endocrine cells into neurons, they co-grafted them, packaged in a retroviral vector, with transgenicastrocytes obtained from the brain's glial white matter, andimplanted with a gene that encodes nerve growth factor.

Then, through a small hole drilled in the skull, they reinsertedthese transgenic astrocytes into the basal ganglia's striatumnigra, site of the body's main dopamine-producing cells.

Rats injected in one brain hemisphere with the neurotoxin 6-hydroxydopamine rotate mindlessly in one direction, providinga living model of Parkinsonism. Grafted with the transgenicastrocytes, their rotational behavior decreased by 40 percent,Cunningham reported, "indicating a partial restoration ofstriatal function." Control animals, which received non-transduced astrocytes, experienced no such improvement.

"Preliminary studies using human fetal astrocytes suggest thatthese are applicable to human cells," Cunningham toldBioWorld.

-- Instead of a retrovirus, which currently is the standardworkhorse of gene therapy vectors, Alfred I. Geller of BostonChildren's Hospital, employed the newly popular herpessimplex virus (HSV-1), stripped of its replication potential. InGeller's Parkinson's-mimicking rats, this vector expressed thegene for tyrosine hydroxylase (TH), the key enzyme indopamine biosynthesis. It too aims to cause dopamineproduction in the striatal neurons and glia, Geller told themeeting here.

Injected with the TH gene expression vehicle, Geller's ratsshowed an 80 percent reduction in assymetrical rotationalbehavior. Control animals, which got the same vector loadedwith the b-galactosidase gene as a placebo, had unchangedbehavior.

"HSV-1 vectors may be a promising new gene therapyapproach to Parkinson's disease," Geller said, but noted thatbefore his technique can go from rodents to humans, the vectorneeds a deletion mutant as a helper virus, which does notrevert to wild type.

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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