A promising tool to potentially correct defective genes withinthe brain is described by three research groups in the March1993 issue of Nature Genetics, released in advance copiesThursday.
The reports focus on using adenoviruses to insert genesdirectly into cells of the central nervous system.
"The news is exciting, novel and of potential use," saidresearcher Beverly Davidson of the University of Michigan.
Her group, and a team led by Marc Peschanski of INSERM inFrance, caused cells to produce an easily visualized protein,beta-galactosidase, for up to eight weeks after injectingadenovirus carrying the gene into the brains of mice or rats. Athird group, led by Ronald Crystal of the National Heart, Lungand Blood Institute in Bethesda, Md., made cells lining brainventricles secrete alpha-1 antitrypsin after injecting the virusinto the cerebral spinal fluid instead of directly into the brain.
Theoretically, transferring genes to the central nervous systemwould permit using genes as a "drug," Crystal's group wrote,"obviating concerns about reactions to the cell delivery systemand the cumbersome aspect of carrying out ex vivo genetransfer."
As a precaution, the viruses are altered so they cannot multiplywithin the cells.
The actual state of the virus in the cell is unknown, pointed outXandra Breakefield, of the Harvard Medical School neuroscienceprogram, in an editorial accompanying the reports. Shecautioned that safety studies are needed to ensure the viruscannot regain the capacity to multiply and spread, that it willnot cause tumor formation and will not incite a cell-slayingimmune reaction.
On the other hand, she noted that adenoviruses seem to cause"robust" production of the protein desired, and appear to causeno harm.
A specialist with herpes virus vectors, which selectively infectneurons, she added that adenoviruses' ability to promoterobust production of a desired protein for a week or longerappears "remarkable" in a variety of nerve cells. Also, inducingongoing production in the cerebral spinal fluid is important, shenoted, because proteins there normally turn over rapidly.
Davidson said it is too early to hope for cures to such diseasesas Parkinson's or Huntington's, but expects gene replacementtherapy researchers will begin long-term studies in animalsthat have inherited metabolic disorders or induced forms ofParkinson's.
Besides potentially breaching the blood-brain barrier fordelivering therapeutic proteins, scientists will be able to usethe viruses to probe how different parts of the brain affect anentire organism.
"This is the first opportunity to understand what's going on invivo," Davidson said. "You can overexpress a gene and look at itin the whole animal, not just in a cell culture. It gives a goodidea of what's going on at a cellular level physiologically."
-- Nancy Garcia Associate Editor
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