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Science Highlights-1999 January 2000 (This continues the series of annual reviews, with slightly different titles, for 1995 through 1998). Stem Cells: Embryonic stem cells can evolve into any type of adult cell, including dopaminergic neurons. But they are now found also in the adult CNS, where they can migrate via the cerebrospinal fluid to any site needing damage repair. This property has been shown in trials with rats, and the race is on to learn how to use it against PD. Stem cells may be taken from discarded embryos of in-vitro fertilization procedures, or from umbilical blood samples taken for routine screening in normal birth deliveries, and have been grown in laboratory culture for nearly a year. Despite these seemingly innocuous sources, there is organized opposition based upon religious belief, to funding of stem cell research. Public funding may be attacked through legislation, corporate funding by economic reprisals such as boycott. Glutamate: Several forms of the neurotransmitter glutamate, particularly N-methyl-D-aspartate (NMDA), in excess seem toxic to dopaminergic neurons, so trials of NMDA inhibitors such as riluzole, memantine, and remacemide in PD are underway. Complex: PD is turning out even more complex than expected. Besides a daunting array of variants (autosomal-dominant, juvenile autosomal-recessive, drug- or environment-induced, etc., there's evidence that the nature of the disease changes as it progresses. In later stages, levodopa becomes less effective, suggesting that other neurotransmitters such as 5-HT become involved. The effect of MPTP is not only immediate parkinsonism, but degeneration that continues to progress after the original insult is removed. Microscope study of PD brains has revealed the shape and direction of progressive neuron loss in the substantia nigra. COMT: Along with decarboxylase and monoamine oxidase, Catechol- O-Methyl Transferase (COMT) is one of three natural defense enzymes that happen also to destroy levodopa or dopamine. Inhibiting COMT, therefore, should benefit in PD by prolonging the effectiveness of levodopa taken to supplement the natural supply of dopamine. Last year Tasmar was restricted because of suspected association with deaths from liver failure, but entacapone (Comtan) seems to lack that risk and became available. Pig Cells: Although no retrovirus infection in human recipients has been found as yet, authorities are still cautious about approving pig cell transplants. Smoking: Lower incidence of PD among smokers (or vice versa) is not just aversion to smoking, it actually seems neuroprotective. Sleep Attacks: Ropinirole (Requip) and pramipexole (Mirapex) have caused sudden sleep attacks (not "drowsiness") that led to accidents while driving. Homocysteine: Levodopa raises level of homocysteine, a major risk factor for heart disease. Levodopa users should ensure that they get enough folic acid, a homocysteine antagonist. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013