UBC Primate Factsheet


TITLE OF RESEARCH: Proteasomal inhibition, aging and Parkinson
Progress Report – Experiment No. L91 – Active (Stage 2) Date Submitted: 2010-04-12 09:49:21


UBC RESEARCHER: Doris J. Doudet, Professor, Medicine/Neurology
Member, Pacific Parkinson Research Centre
Member, UBC Brain Research Centre, UBC-TRIUMF Group

ANIMALS USED IN EXPERIMENTS: 4 – 8 non-human primates (both specified)

AREA OF RESEARCH: Experimental models of mood and movement disorders. In this protocol, Dr. Doudet and her team at TRIUMF/UBC are attempting to create in non-human primates a new, progressively degenerative ‘model’ of Parkinson’s Disease. They hypothesize that long term administration of low doses of protease inhibitor drugs into the brain will impair the monkeys and lead to a simulation in the animal of the “behavioral, chemical and pathological features of PD”. (1)

FUNDING SOURCE: Canadian Institutes of Health Research (CIHR) Team Grant from 2006-04-01 to 2011-03-31. (Jonathan A. Stoessel is Principal Investigator of CIHR Team in Parkinson’s Disease and Acting Head, Div. of Neurology, UBC), Titan Pharmaceuticals (now owned by Bayer)

DESCRIPTION OF EXPERIMENT: Proteasome inhibitors are drugs that block the action of proteasomes, cellular complexes that break down proteins. Dr. Doudet’s current experiment uses rhesus monkeys which are receiving injections of proteasomal inhibitors into their brains. Headholding devices have been surgically implanted into the monkeys’ brains, and protrude from the top of the monkeys’ heads, to be hooked up to frames when the researchers want to totally immobilize the animals presumably for injection of drugs and for scans at 3, 6, 9 and 12 months. The monkeys have been scanned after implantation but before injection, for baseline (or starting point) information. Some animals are to be killed at 6 months, some at 12 months.

NOTES: According to TRIUMF/UBC this work, using PET imaging tools that are well established at TRIUMF/UBC, has “great potential for future grant funding, such as NIH” and on this basis has been awarded High Priority.

RECENT RESEARCH: Dr. Doudet has long been investigating the effects of electroconvulsive therapy and dopamine inhibition in rat and non-human primate models of Parkinson’s Disease, depression and drug abuse. A recent experiment was titled “In vivo Study of the Direct and Indirect Striatal Output Pathways in Mild and Severe Primate Models of Parkinson.” D. Dr. Doudet induced ‘parkinsonism’ by injecting toxins into monkeys’ brains to destroy essential dopamine-producing cells.

However, symptoms of this drug-induced parkinsonism bear only a superficial resemblance to human Parkinson’s Disease. “Primates do not get PD, and the crude way in which its symptoms are modelled bear little relation to the gradual onset of the condition in humans.” (BUAV Report: Ending Primate Experiments, publ. 2007)
“The cause of PD is specific – it’s caused by degeneration of a specific part of the brain. Animals don’t get it, and the best animal experimenters have managed to do is recreate some of the symptoms.”

NOTE: Many scientists question the use of animals in PD research and point to important breakthroughs achieved without the use of animal models:
“Deep Brain Stimulation, for instance, was based upon a serendipitous discovery in a human patient.”
Cooper, I., (1953) Ligation of the anterior choroidal artery for involuntary movements:
parkinsonism. Psychiatry Q, 27:317-9 (also presented in BUAV Report, 2007)

RECENT PUBLICATION: Electroconvulsive Therapy Alters Dopamine Signaling in the Striatum of Non-human Primates, A. M. Landau, M. Mallar Chakravarty, C. M. Clark, A. P. Zis and D. Doudet, Neuropsychopharmacology (2010), I-8

PAPERS IN PREPARATION: The following titles are currently in preparation from previous Life Sciences Projects TRIUMF Evaluation Committee studies involving Dr. Doudet:

Electroconvulsive therapy induces alterations in the dopaminergic system in the striatum of non-human primates: a PET study. (A. Landau, M.Chakravarty, C. Clark, A. Zis. DJ Doudet)

Mapping Abnormal Metabolic Brain Function in Parkinsonian Macaques: A FDG PET Study (Y. Ma, S. Peng, J. Flores, V. Sossi, D Eidelberg, DJ Doudet)
(1), (2), (3) http://www.triumf.ca/sites/default/files/LSPEC%20Report_April%202010_2.pdf