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CURRENT SCIENCE REVIEWS By Joe Bruman May 2000 Page 1 of 4 BMJ, 25 March 2000:825(news item); PPL Therapeutics at Blacksburg, VA successfully cloned 5 pigs from a single adult, as the first step toward commercially viable organ and tissue replacement in human patients. The next step is to endow the clones with a "knockout" of the gene for an enzyme that triggers the human immune reaction, thereby preventing the rejection of transplanted material. Cooper D et al; BMJ, 25 March 2000:868-869: Debate over xenotransplantation in general and pig tissue transplants in particular (CSR MAR 00, APR 00) heats up. Advocates cite the enormous potential benefit; opponents cite corporate greed, and the risk of an as yet unknown retrovirus gaining a foothold that may threaten the entire human race. Friedman J, Factor S: Mov Disord 2000;15:201-211: They studied all the reports they could find about atypical antipsychotics for treatment of drug-induced psychosis in PD. They comment on several, and offer suggestions about the general strategy of drug therapy for PD, to be followed until an antipsychotic becomes needed. Kuopio A et al; Mov Disord 2000;15:216-223: By standardized techniques they assessed quality of life in a community-based sample of 228 PD patients. Aside from the decline in motor function, depression was the main factor. Hagell P et al; Mov Disord 2000;15:224-229: Study of 5 PD recipients of bilateral intrastriatal embryonic tissue transplants showed improved quality of life, mostly in the areas of mobility, emotional reactions, and energy. Baron M et al; Mov Disord 2000;15:230-237: A 4-year followup of 10 PD recipients of unilateral postero- ventral pallidotomy showed that although some motor symptoms tend to return to pre-surgery baseline, most patients feel that quality of life continues better than before. Caviness J et al; Mov Disord 2000;15:238-243: They used computerized quantitative electromyography (QEMG) in PD patients to look for motor neuron degeneration in sporadic idiopathic PD. Although clinically silent, it seems to be a normal component of PD. Forssberg H et al; Mov Disord 2000;15:244-254: In trial with 10 PD subjects and 20 controls of action tremor during the hand task of grasping and lifting an object, they conclude that the action tremor of PD is an exaggerated form of physiological tremor. Elble R, Leffler K; Mov Disord 2000;15:255-268: They had Alzheimer's patients, PD patients, and controls push or pull with specified force on a rigid bar while standing. They conclude that the slower response of both AD and PD patients may be relevant to the tendency to fall. CURRENT SCIENCE REVIEWS By Joe Bruman May 2000 Page 2 of 4 Leopold N; Mov Disord 2000;15:301-304: Trial of the new neuroleptic risperidone (Risperdal) in 39 PD patients having drug-related hallucinations showed some improvement, without significant effect on UPDRS scores. Zesiewicz T et al; Mov Disord 2000;15:305-308: Open-label test of sildenafil citrate (Viagra) in 10 male PD patients showed significant improvement of sexual function. Kampoliti K et al; Mov Disord 2000;15:309-312: They tested the effect of visual stimuli (a laser beam and a modified inverted stick) on walking ability of 28 PD patients subject to "freezing" episodes during the "on" phase. Neither device was consistently helpful, but authors suggest cautious trial in individual cases. Giovannoni G et al; J Neur N'surg Psych 2000;68:423-428: They found and studied 15 advanced-PD patients getting dopamine- replacement therapy, who had become addicted to those drugs, developing tolerance to excessive dosage as well as typical psychiatric signs of addiction. Cummings J; J Neur N'surg Psych 2000;68:404 (editorial): Comment on item above. It seems that addiction to dopaminergic drugs themselves is quite rare among PD patients, but dopamine may play an important role in addiction to other substances. Araki I, Kuno S;J Neur N'surg Psych 2000;68:429-433; Using the international prostate symptom score from a standard questionnaire given to 203 successive visiting PD patients, they found 55 (27%) to have symptomatic voiding dysfunction. Wenning G et al;J Neur N'surg Psych 2000;69:434-440: Multiple system atrophy (MSA) is hard to distinguish from PD by clinical features alone, partly because of its rarity. But comparison of 138 cases (confirmed postmortem) revealed that preserved cognition and absence of medication-induced psychosis are favored in MSA. Tan E et al;Neur 2000;54:1195-1198: They looked for a certain gene mutation, associated with sporadic PD, in essential tremor patients and Huntington's patients as well as a large sample of PD patients, and found it in some ET but not in the HD or control groups. Jacobs H et al;Neur 2000;54:1208 (correspondence): They observed that siblings of patients with dementia and PD are 3 times as likely as siblings of normal subjects to develop Alzheimer's disease. Harhangi B et al;Neur 2000;54:1272-1276: Allele APOE-e4 is associated with both Alzheimer's and Lewy-body disease, which have motor and cognitive features in common with PD. So they studied DNA of PD patients among some 7000 elderly Rotterdam residents, finding also that APOE-e2 increases the risk of dementia in elderly people who have PD. CURRENT SCIENCE REVIEWS By Joe Bruman May 2000 Page 3 of 4 Kaasinen V et al;Neur 2000;54:1482-1487: By means of PET scans using a novel tracer to study D2 and D3 dopamine receptors in 14 unmedicated early-PD patients, 14 advanced-PD patients taking levodopa, and 20 normal controls, they found that advanced PD affects D2/3 receptors not only in areas related to motor control, but also in areas related to cognitive function, such as the prefrontal and cingulate cortex. (author not listed);Neur 2000:54:1583-1588: To check out evidence that inhibiting glutamate as well as restoring dopamine may be of use in PD, they did a preliminary (successful) safety and tolerability trial of the NMDA-blocker remacemide on 200 unmedicated new PD patients. Dosages evidently were too low for significant effect on PD symptoms. Konitsiotis S et al;Neur 2000:54:1589-1595: They tested an agonist and a noncompetitive antagonist of the glutamate AMPA in parkinsonian (MPTP) monkeys. The former worsened dyskinesia, while the latter reduced it, and improved PD motor symptoms as well. Hughes T et al;Neur 2000;54:1596-1603: A 10-year study of 83 PD patients and 50 controls for incidence and prognostics revealed that dementia in PD is age-related just as in non-PD, and not significantly related to age at PD onset. Gouider-Khouja N et al;Neur 2000;54:1603-1609: An interview study of 133 members of 21 Tunisian families, including 88 PD cases both familial and sporadic, showed no special pattern of clinical features other than younger onset, and both dominant and recessive inheritance, in familial PD. Lee C et al;Ann Neur 2000;47:493-503: Positron-emission tomography (PET) of 35 PD patients and 16 controls suggests that PD includes compensatory changes in presynaptic dopaminergic nerve terminals. Wakabayashi K et al;Ann Neur 2000;47:521-523: Synphilin-1, a novel protein previously found in association with a-synuclein, was found by several study methods to be present in Lewy bodies of patients with PD. Morino H et al;Ann Neur 2000;47:528-531: Analyzing DNA of 172 patients and 132 normal controls, they found that one of the two polymorphisms (mutations) of the dopamine-transporter gene is negatively associated (i.e., less frequent) in subjects with PD. Olanow C et al;Ann Neur 2000;47;Supplement 1:S1-S203: Papers (reviewed in a separate document) presented at the 20-22 November 1998 conference in Bermuda, on dyskinesia in PD. While the general state of knowledge then is impressive, advances in the short time since then are even more so. CURRENT SCIENCE REVIEWS By Joe Bruman May 2000 Page 4 of 4 Eskandar E et al;J Neurosurg 2000;92:375-383: Two-year followup of 75 successive recipients of unilateral pallidotomy, guided by MRI and macrostimulation but not microelectrode recording, showed the protocol to be safe and effective treatment for advanced-stage PD. Bejjani B et al;J Neurosurg 2000;92:615-625: They report 12 advanced-PD patients who received bilateral subthalamic neucleus stimulation implants guided by stereotactic MRI, macrostimulation, and electrophysiological guidance [microelectrode recording]. At 6-month followup, all showed varied but generally good results. Nakao N et al;J Neurosurg 2000;92:659-670: Cultured embryonic cells, genetically modified to produce glial- cell-line-derived neurotrophic factor (GDNF) were implanted in the midbrain of rats which were then rendered parkinsonian. After 4 weeks the cells had thrived, and prevented further damage to nigrostriatal neurons, indicating promise for this new method of delivery. -- J. R. Bruman (818) 789-3694 3527 Cody Road Sherman Oaks, CA 91403-5013