SCIENCE AND MEDICINE
Early days for neuronal grafting in stroke
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estoration of function after stroke is the ideal goal of therapy, and neuronal transplants have restored function in animal models, though the mechanism is not fully understood. Now, a US team reports that neuronal grafting is feasible and safe in human beings, with clinical evidence of efficacy in 50% of patients. Safety of neuronal grafting is a key issue since the suspension of a phase-I study of porcine fetal neurons in April due to adverse events (www.diacrin.com/stroke1.htm). The approach taken by Douglas
Kondziolka (University of Pittsburgh Medical Center, PA, USA) and colleagues involves cultured human neurons, derived from embryonic carcinoma cells (Layton BioScience, CA, USA). 12 patients with stable motor deficits at least 6 months after basal ganglia stroke received 2–6 million neurons by stereotactic injection, plus cyclosporine-A. One patient had a seizure 6 months aftre the operation, but no adverse events were thought to be related to the grafts. At 6 months postimplantation, European Stroke
Bone marrow hopeful source for neurons Adult bone-marrow stromal cells can be prompted to become neurons, and in the future “may constitute an abundant and accessible cellular reservoir for the treatment of a variety of neurologic diseases”, report Dale Woodbury (University of Medicine and Dentistry of New Jersey, NJ, USA) and co-workers. The team cultured pluripotent rat marrow stromal cells (MSCs) in various media. Shortly after the addition of antioxidants, up to 80% of MSCs exhibited neuronal characteristics and increased expression of neuron-specific proteins. Similar changes were seen with MSCs from an adult human donor (J Neurosci Res 2000; 61: 364–70). The next goal is to demonstrate that these cells function as neurons, says Woodbury. If so, their use may circumvent both safety concerns over malignancyderived cell lines and “the moral and ethical issues associated with the use of fetal tissues for the harvesting of stem cells”, says Woodbury.
Scores had improved at least three points in six patients. Positron emission tomography confirmed increased glucose uptake at the implant site in four of these six patients and two others (Neurology 2000; 55: 565–69). The team is now planning a controlled, multisite, dose-response trial. However, “there are reasons to have reservations about these findings”, writes Justin Zivin (University of California at San Diego, CA, USA) in an editorial. One major safety issue remaining after 1 year follow-up is the potential for malignant transformation of cell lines, he suggests, although no malignancies have been reported in animal models so far, note the study authors. Zivin follows other experts in asserting that “there is little reason to believe that [transplanted cells] will readily make proper connections among the denervated targets”. Together, these concerns mean that “considerable time and effort” will be needed to demonstrate that this technique is both safe and effective.
Kelly Morris Kelly Morris
Beer smell repels children of drinkers oung children whose parents drink to escape feelings of unhappiness are apt to dislike the smell of beer, suggesting a learned aversive response to alcohol, report US researchers. “It was a simple study, but I think the children told us something pretty powerful”, says lead author Julie Mennella (Monell Chemical Senses Center, Philadelphia, PA, USA). Mennella and colleague Pamela Garcia gave 83 girls and 67 boys, aged 3 to 6 years, plastic squeeze bottles; odours of beer, bubble gum, sour milk, and mineral oil (neutral) were delivered in gentle puffs to the nostrils. If children liked a smell, they passed the bottle to a stuffed Big Bird toy; if they disliked it, they passed the bottle to an Oscar-the-Grouch toy for disposal. Separately, the children’s parents answered questions about alcohol use. 86% of children liked the smell of bubble gum and 89% disliked the smell of sour milk. About half (53%) liked the beer odour—but when data were grouped according to parental
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THE LANCET • Vol 356 • August 26, 2000
drinking habits, a significant difference emerged: only 27% of children with parents who drank to escape liked the smell of beer, compared with 66% of those whose parents were not escape drinkers (Alcohol Clin Exp Res 2000; 24: 1167–71). Memories evoked by odours are particularly emotionally charged, says Mennella, because of a “unique interconnection” between the olfactory and limbic systems (Lancet 1999; 354: 2142). “If you want to educate children of this age about drinking, it’s important to tap into how they feel about it, because this might take you on a different path.” “It’s intriguing to see a pronounced response to a parent’s drinking in children so young”, comments Ann Bradley of the National Institute on Alcohol Abuse and Alcoholism (Bethesda, MD, USA). “But whether the aversion can or should be maintained in multiple environments along the life course is an open question.”
News in brief Super muscle to the rescue Researchers from the Cape Western Reserve University, Ohio, USA, have discovered that migraine sufferers substantially improve after surgical removal of the corrugator supercilii muscle during certain procedures. The branch of the trigeminal nerve that penetrates this muscle is perhaps “pinched” by the muscle, say the investigators, initiating the cascade of biochemical events that lead to the migraine (Plast Reconstr Surg 2000: 106; 428–33). Nicotine rewards Brief exposure to low levels of nicotine can cause lasting changes in the brain’s reward areas, report scientists from the University of Chicago, IL, USA. They found that nicotine enhanced connections between rat neurons that are sensitive to the drug and other nerve cells that register pleasure. Uncovering nicotine’s cellular effect may help to formulate precise targets for drugs to combat addiction (Neuron, August 24, 2000).
Marilynn Larkin
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