GM mice suffer in crude experiments supported by the Alzheimer’s Society

Introduction

The Alzheimer’s Society has co-funded a series of profoundly disturbing experiments on genetically modified (GM) mice, which were conducted at the University of Ulster.[1][2]The mice, who were genetically altered to develop a crude approximation of Alzheimer’s disease, were injected daily with a drug currently used to treat diabetes in humans, then subjected to a regime of highly stressful behavioural tests which involved being forced to swim around in a pool of water looking for an escape route. The research was investigating whether a drug used to treat Type 2 diabetes could help to reduce the symptoms of Alzheimer’s that the mice exhibited.[3]

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Animal suffering

  • The experiments used GM mice who had been engineered to suffer from some of the symptoms of Alzheimer’s, and non-GM (wild-type) mice to act as a control group. During the breeding process for this particular type of GM mice, many animals can experience seizures and death.[4]
  • To work out whether the animals’ genes had been successfully altered, all mice were subjected to a painful procedure known as ear punching.
  • Prior to the experiments starting, the mice were kept in single cages, which would have denied these social animals their most basic behavioural needs. The RSPCA states that housing social animals without companions ‘will seriously limit the animals’ ability to express their natural behaviour and will have a big impact on their welfare’.[5]

The experiments

  • Twelve of the mice endured eight weeks of daily injections into their abdomen, with a drug used to treat Type 2 diabetes in humans. A further group of twelve mice were injected with saline solution.
  • The mice were then subjected to several rounds of behavioural tests, including: 
  1. Being placed in an aluminium ‘arena’ where their ability to explore objects was measured, as well as signs of anxiety such as grooming and defecation.
  2. Morris water maze testing, which involved the mice being forced to swim around in a pool of water looking for an escape route. This test has been recognised as causing unavoidable stress.[6] In subsequent tests, the researchers changed the location of the escape route or removed it completely. The behavioural tests took place over more than a week, sometimes with several challenges per day.
  • When the behavioural tests ended, the mice were anaesthetised and holes were drilled into their skulls so that electrodes could be inserted and record brain activity. They were then killed using a gruesome procedure designed to drain their blood but preserve their tissues[7] and their brains were removed for examination.

 

Faulty Science

  • The drug being tested on the mice is already used to treat diabetes in humans, so we already know that it is safe in people. Therefore a much more relevant approach would have been to study the effects of the drug on volunteers with Alzheimer’s disease, many of whom would no doubt be keen to try out a treatment that could help them. The drug is now being tested in human clinical trials, which shows that this approach is indeed feasible. [8]
  • Numerous experiments on mice, both by these and other authors, have already tested this particular drug and others like it.[9]
  • The symptoms bred into the GM mice represent only a crude approximation of Alzheimer’s disease. A recent review paper looked at transgenic mouse ‘models’ of Alzheimer’s (like those used in this experiment) and concluded that ‘none of the models fully recapitulates AD (Alzheimer’s Disease)’.[10]
  • There is no cure for Alzheimer’s, which currently affects up to 35 million people worldwide.[11] Decades of research have produced numerous potential treatments that appeared successful in animal tests but went on to fail in human clinical trials.[12] Out of 244 potential treatments tested between 2002-2012, only one was approved, meaning that more than 99 per cent of them failed.[13]
  •  A recent example of failure is the drug bapineuzumab. This appeared successful when tested on GM mice (a similar type to those used in the experiments exposed here) but the drug went on to fail in human clinical trials.[14] [15]
  • A major focus of the study is that the drug appeared to reduce abnormal deposits of protein (amyloid plaques) in the brains of the mice. These abnormal deposits are also found in humans with Alzheimer’s, but researchers are becoming increasingly uncertain that these plaques even represent a key target in fighting the disease.[16]
  • One of the authors of the study is named as an inventor on a patent application for using the type of drug under investigation to treat neurodegenerative diseases. In our view, this represents a potential conflict of interest.

Additional information and background notes

  • Research has suggested that there can be significant differences in the results produced by male and female mice of this type. The current experiments used only male mice, so females could have produced a different result. [17] [18]
  • Alzheimer’s disease derives its name from Dr. Alois Alzheimer, who established its existence through psychiatric observation of his patients and use of post mortem tissue samples to examine and identify two different types of protein deposits in the brain that are characteristic of Alzheimer’s.[19] This illustrates the importance of focusing on patients, not crude animal ‘models’, in developing our understanding of the disease.
  • Mainstream clinical media report studies into Alzheimer’s on mice with caution, stating that ‘Although we can study the mice’s ability to negotiate a maze and avoid electric shocks, it is more difficult to assess higher and more complex human brain functions that are affected in Alzheimer’s, such as language and personality.’ Key species differences between mice and humans are also highlighted. These include brain size and structure, levels of immune response and plaque formation in the brain – differences that occur when natural levels in humans are compared with those to be found in animals with the artificially created condition.[20]
  • The discovery of new links between Alzheimer’s and diabetes is repeatedly claimed to be due to animal studies, for example most recently in mice [21] and previously in worms [22]. Yet research from post mortem studies in human brains, brain imaging data and studies involving Alzheimer’s and diabetic patients had established a link several years earlier, leading to Alzheimer’s being referred to as ‘Type 3 diabetes’. [23] [24] [25] [26] If further elucidation is required, it should be sought in non-invasive human studies.

[1] McClean P et al (2013). Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer’s disease. Neuropharmacology. 76 Pt A:57-67 [http://dx.doi.org/10.1016/j.neuropharm.2013.08.005]

[2] Alzheimer’s Society, Testing the effects of insulin-like drugs on Alzheimer’s disease [http://www.alzheimers.org.uk/site/scripts/documents_info.php?documentID=601]

[3] McClean P et al (2013). Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer’s disease. Neuropharmacology. 76 Pt A:57-67 [http://dx.doi.org/10.1016/j.neuropharm.2013.08.005]

[4] The Jackson Laboratory, Mouse strain datasheet [http://jaxmice.jax.org/strain/005864.html]

[5] Lane N, Jennings M (2004). Supplementary resources for lay members of Local Ethical Review Processes: Projects involving genetically modified animals. RSPCA Research Animals Department [http://www.rspca.org.uk/servlet/BlobServer?blobtable=RSPCABlob&blobcol=urlblob&blobkey=id&blobwhere=1105990223463&blobheader=application/pdf]

[6] Tanila H (2012). Wading pools, fading memories – place navigation in transgenic mouse models of Alzheimer’s disease. Front Aging Neurosci. 4:11 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365277/]

[7] University of California, Institutional Animal Care and Use Committee (IACUC), Vascular perfusion with fixatives for tissue collection [http://www.iacuc.ucsf.edu/Policies/awSPfixative.asp]

[8] ClinicalTrials.gov, Evaluating Liraglutide in Alzheimer’s Disease (ELAD) [https://clinicaltrials.gov/ct2/show/NCT01843075]

[9] Search of PubMed database [http://www.ncbi.nlm.nih.gov/pubmed/?term=H%C3%B6lscher+C[Author]

[10] Langley G (2014). Considering a new paradigm for Alzheimer’s disease research. Drug Discovery Today. 19(8):1114-24 [http://www.sciencedirect.com/science/article/pii/S1359644614000907]

[11] Anstey K (2013). Development of a new method for assessing global risk of Alzheimer’s disease for use in population health approaches to prevention. Prev Sci. 14(4):411-21 [http://www.ncbi.nlm.nih.gov/pubmed/23319292]

[12] PM Live, Alzheimer’s disease pipeline takes multiple hits [http://www.pmlive.com/pharma_news/alzheimers_disease_pipeline_takes_multiple_hits_493398]

[13] Scientific American (July 2014), Why Alzheimer’s drugs keep failing [http://www.scientificamerican.com/article/why-alzheimer-s-drugs-keep-failing/]

[14] Reuters (August 2012), Pfizer, J&J scrap Alzheimer’s studies as drug fails [http://www.reuters.com/article/2012/08/07/us-pfizer-alzheimers-idUSBRE8751F120120807]

[15] MD Lingo (March 2014), Bapineuzumab not an effective treatment for Alzheimer’s disease [http://www.mdlingo.com/article/bapineuzumab-not-an-effective-treatment-for-alzheimers-disease]

[16] Drachman D (2014). The amyloid hypothesis, time to move on: Amyloid is the downstream result, not cause, of Alzheimer’s disease. Alzheimer’s & Dementia.10(3):372-80 [http://www.sciencedirect.com/science/article/pii/S1552526013029142]

[17] Cheng D et al (2014). Novel behavioural characteristics of female APPSwe/PS1ΔE9 double transgenic mice. Behav Brain Res. 1;260:111-8 [http://www.ncbi.nlm.nih.gov/pubmed/24315833]

[18] Cheng D et al (2013). Novel behavioural characteristics of the APP(Swe)/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. Behav Brain Res.15;245:120-7 [http://www.ncbi.nlm.nih.gov/pubmed/23419740]

[19] Alzheimer’s Disease International, Alois Alzheimer [http://www.alz.co.uk/alois-alzheimer]

[20] NHS Choices (March 2015), Ultrasound ‘breakthrough’ in treating Alzheimer’s – in mice [http://www.nhs.uk/news/2015/03march/pages/ultrasound-breakthrough-in-treating-alzheimers-in-mice.aspx]

[21] Washington University in St Louis Dept of Genetics, Scientists find new link between diabetes and Alzheimer’s [http://genetics.wustl.edu/blog/scientists-find-new-link-between-diabetes-and-alzheimers/]

[22] BBC News (June 2012), Alzheimer’s gene ‘diabetes link’ [http://www.bbc.co.uk/news/health-18445701]

[23] Janson J et al (2004). Increased risk of Type 2 diabetes in Alzheimer disease. Diabetes. 53(2):474-81 [http://diabetes.diabetesjournals.org/content/53/2/474.long]

[24] Korf E et al (2006). Brain aging in very old men with type 2 diabetes: the Honolulu-Asia Aging Study. Diabetes Care. 29(10):2268-74 [http://www.ncbi.nlm.nih.gov/pubmed/17003305/]

[25] De la Monte S et al (2008). Alzheimer’s Disease Is Type 3 Diabetes – Evidence Reviewed. J Diabetes Sci Technol. 2(6): 1101–1113 [http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2769828/]

[26] Leibson C et al (1997). Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol. 15;145(4):301-8. [http://www.ncbi.nlm.nih.gov/pubmed/9054233]

 

 

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