Cruel experiments on marmosets supported by Cure Parkinson’s Trust
Animal Aid has uncovered two shocking charity-funded experiments on monkeys that involved the animals being brain-damaged through the use of a toxic chemical called MPTP that can leave them severely disabled. They were then dosed with the Parkinson’s drug L-DOPA as well as one of two experimental compounds: the recreational drug ecstasy (MDMA) or a derivative. Eleven monkeys were used in all, six of whom had previously been subjected to similar experiments. Although the studies were conducted in Canada, a source of funding was the Cure Parkinson’s Trust, a UK charity that fundraises in this country.
Animal Aid, over many years of monitoring reports of Parkinson’s-related primate experiments, has not encountered one where the monkeys have been re-used. The Home Office has confirmed that experiments in which monkeys are brain-damaged with MPTP fall into the highest category of severity. It has previously stated that brain-damaging monkeys with MPTP has ‘devastating welfare costs’ for the animals involved and serious questions arise as to whether the re-use of primates in such harmful experiments would be permitted in the UK, or in the other EU countries governed by the same European directive.
Experiment 1: Characterization of 3,4-Methylenedioxymethamphetamine (MDMA) Enantiomers In Vitro and in the MPTP-Lesioned Primate: R-MDMA Reduces Severity of Dyskinesia, Whereas S-MDMA Extends Duration of ON-Time
Co-funded by: Cure Parkinson’s Trust
Published: The Journal of Neuroscience, 2011
Experimental protocol: Six marmoset monkeys were injected daily for five days with the brain-damaging chemical MPTP until they developed severe Parkinson’s disease (PD) like symptoms. Poisoning marmosets in this way can produce symptoms that, at their most extreme, leave the animals essentially paralysed, rigid, mute and unable to feed or groom themselves. Over the next 12 weeks, the marmosets’ parkinsonian symptoms were left to develop fully and stabilise. They were then given the standard Parkinson’s drug L-DOPA, in such high doses that they developed a range of serious side effects of the sort that will often take years to appear in human PD patients when they are administered the drug. Among the adverse reactions were uncontrolled movements (dyskinesia) and psychotic behaviours that could include hallucinations. The monkeys were also administered ecstasy to see whether it could moderate the adverse reactions to L-DOPA, while also prolonging its beneficial effects. On days of ‘behavioural assessment’, monkeys received the L-DOPA in combination with one of two forms of the street drug or with a neutral substance. They were then confined in cages, alone, for six hours so that their ‘movement disorders’ and other disabling symptoms could be recorded. The researchers make it clear that the monkeys had been used in ‘previous studies’ of a similar nature. The same research team also used rats as a source of brain tissue. Rats were killed by decapitation after exposure to carbon dioxide. This method of killing is as cruel as it is violent. It has been known in the UK since 2004 that carbon dioxide causes considerable distress to rodents in the laboratory and should therefore not be used for the purpose of euthanasia.
Results: The two forms of ecstasy employed in the experiment produced different results. So called R-MDMA was reported to have reduced the severity of L-DOPA-induced involuntary movement side effects (dyskinesia) but did not prolong its beneficial effects. The other form of the drug, S-MDMA, was said to have extended the benefits of L-DOPA but made worse the side effects.
Scientific problems with MDMA use (see also ‘Scientific validity…’ below): MDMA has been used by other researchers on MPTP-damaged monkeys in a similar manner. But the sticking point then, as with the latest research, is that the drug cannot not be used on human Parkinson’s patients because of its toxic effect on the brain and due to its psychoactive nature. Recognised side effects of ecstasy include anxiety, paranoia, depression, exhaustion, dizziness and insomnia. Indeed, a 2003 study that involved giving MDMA to MPTP-poisoned marmosets states: ‘MDMA will never become a treatment for the complications of PD.’ Although the authors of the 2003 study suggest MDMA exerts a pharmacological effect on certain chemical receptors, they make it clear that the drug itself has little therapeutic potential.
Experiment 2: The Monoamine Re-Uptake Inhibitor UWA-101 Improves Motor Fluctuations in the MPTP-Lesioned Common Marmoset
Co-funded by: Cure Parkinson’s Trust
Published: PLoS ONE, 2012
Experimental protocol: The second, related experiment used five female marmosets. They were again dosed with MPTP, and monitored for 12 weeks while the PD-like symptoms ‘developed and stabilised’. The procedure then followed in a similar way to the first, except ecstasy was replaced by a chemically similar experimental drug known as UWA-101, a derivative of ecstasy. After MPTP came dosing with L-DOPA and UWA-101. Once again, the monkeys suffered uncontrolled movements and psychosis – symptoms that were assessed for hours at a time while the monkeys were held in solitary confinement in observation cages.
Results and scientific problems with UWA-101 use (see also ‘Scientific validity…’ below): Though the researchers reported more favourably on the combined usage of L-DOPA and UWA-101, compared with ecstasy, they pointed to a fundamental problem. This was that the ‘severity of psychosis-like behaviours’ increased at higher doses. They were also concerned as to whether the beneficial effects they did detect would last with long-term usage of the drug. They nonetheless remain hopeful that it can be developed for clinical use. However, other drugs belonging to the same class as UWA-101 (monoamine re-uptake inhibitors) have been ‘highly effective’ at reversing motor disability in MPTP-poisoned marmosets, but failed to show any benefit in early human clinical trials. In a 2011 review co-authored by a prominent Parkinson’s researcher, this is described as ‘a notable failure that urges caution in interpreting everything coming from MPTP-treated primates’. If the compound does turn out to be beneficial it would only be after having proved itself in trials involving human tissue, or through its use in actual patients. Neurological research using animals is replete with false dawns.
Scientific validity of the animal model: The problem lies in the deficiency of the animal model itself. Monkeys are regarded as the best human surrogates but, as stated by the Executive Director of the Parkinson’s Disease Foundation (an influential US charity): ‘Mice don’t get Parkinson’s. Nor, for that matter, do monkeys. Yet these are the organisms in which the tests are done before new drugs are tested in people. What this means is that just because something works in a mouse or a monkey doesn’t mean that it will work in a human’. In fact, over time monkeys can recover from the damage inflicted on them, unlike human patients with the disease. Dr Marius Maxwell, an Oxford, Cambridge and Harvard-trained neurosurgeon, has strongly criticised, on scientific grounds, the use of brain-poisoned monkeys as a ‘model’ for PD research. He states: ‘There is no evidence to suggest their overall predictive concordance to human PD treatment…would exceed the best case 50:50 coin toss probability.’
Even the influential 2006 Weatherall Report (an evaluation of the use of monkeys in research), lists what some of its respondents regard as multiple and significant deficiencies of the non-human primate model of PD. They include:
- PD patients and monkeys differ in the onset, type and persistence of symptoms
- Degeneration of nerve cells in a particular area of the human brain (the corpus striatum) is associated with dyskinesia, but monkeys do not suffer from dyskinesia when this area of their brains is damaged
- The progression of PD is slow and chronic, whereas the symptoms experienced by the monkeys are acute and severe
- The animal model does not allow for the study of genetic, age-related and environmental factors
- Other signs of PD, such as those relating to cognition and emotion, are difficult to evaluate in animals
A 2012 review mentions further deficiencies of the MPTP-poisoned primate model of PD. One of the most significant is the lack of Lewy bodies, a pathological hallmark of PD that is found in the brains of humans but not of MPTP-poisoned monkeys. Another important point highlighted by the review is that brain-poisoned marmosets do not get rest tremor, a key symptom of the disease experienced by human patients.
- In a judicial review against the Home Secretary by the British Union for the Abolition of Vivisection the then chief Home Office inspector referred to the ‘devastating welfare costs’ for monkeys poisoned with MPTP
- Universities Federation for Animal Welfare (2004). Press Release – Carbon dioxide ‘causes laboratory rodents considerable distress’ [online] http://www.ufaw.org.uk/pdf/ufaw-pr-carbon-dioxide.pdf
- Iravani M, Jackson M, Kuoppamäki M et al. (2003). 3,4-Methylenedioxymethamphetamine (Ecstasy) Inhibits Dyskinesia Expression and Normalizes Motor Activity in 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine-Treated Primates. Journal of Neuroscience. 23(27): 9107-9115
- Duty S, Jenner P (2011). Animal models of Parkinson’s disease: a source of novel treatments and clues to the cause of the disease. British Journal of Pharmacology. 164 1357–1391
- Parkinson’s Disease Foundation (2011) The Problem of Failed Trials- and One Piece of the Solution [online] http://www.pdf.org/fall11_failed_trials_solutions
- Mounayar, S. et al (2007) A new model to study compensatory mechanisms in MPTP-treated monkeys exhibiting recovery. Brain. 130(Pt 11): 2898-914
- Maxwell M (2006). Oxford vivisectionists are swimming against the tide [online] https://www.animalaid.org.uk/oxford-vivisectionists-swimming-tide-marius-maxwell/
- Weatherall Report (2006) [online] http://www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC003440
- Porras G, Li Q, Bezard E (2012). Modeling Parkinson’s disease in primates: The MPTP model. Cold Spring Harb Perspect Med 2012;2:a009308