SPEAK -

3 August, 2007.

For the attention of Dr John Richmond,
Chief Home Office Inspector,
ASP Division

Dear Dr Richmond,

I am contacting you pursuant to a response received to a request for information under the Freedom of Information Act 2000 concerning a Home Office Application project licence. The information in question was supplied by the freedom of information officer at the University of Oxford on 24 January 2007 and additionally, on 11 April 2007. The FOIA request stems from a BBC2 documentary, 'Monkeys, Rats and Me', aired on 27th November, 2006, featuring an experimental program to be conducted by Prof. Tipu Aziz on the macaque monkey, 'Felix'.

According to the first of these two FOIA documents (24 January), the licence lists five specific objectives:

'The first four objectives are to elucidate the underlying anatomy and pathology of a particular area of the brain stem in the non-human primate, to determine its role in proximal limb movements, both in the normal and in the Parkinsonian condition, and to determine if it can be influenced by intervention in order to overcome movement problems caused by Parkinson's disease. The fifth objective is to determine the utility of autologous stem cell transplant in the treatment of Parkinson's disease'.

The second (11 April) of these two FOIA documents states, 'All applicants for a Home Office project licence are required to demonstrate that the research programme cannot be achieved satisfactorily by methods that do not involve the use of animals'.

With respect to the first four stated objectives of the study:

1. The anatomy and pathology of the brain stem area under investigation have already been studied extensively in human subjects and documented in the scientific literature (1-15). Since the architectonic organisation of the brain differs significantly between macaque monkey and human brain (16-22), and the purported aim of this research is intended to benefit people, why grant a licence to study the monkey brain invasively?

2. The main objective of the study - to test whether electrical stimulation of the pedunculopontine nucleus (PPN) can alleviate the akinesia (loss of movement) caused by Parkinson's disease - has also previously been studied in human subjects and documented in the scientific and medical literature (1-15). This includes previous studies conducted by the project licence holder himself, in non human primates (23).

3. With respect to the fifth stated objective of the study, autologous stem cell transplants have already been conducted in both animal and human subjects, with varying degrees of success. Proof-of-principle using autologous bone marrow-derived mesenchymal stem cells (MSCs) has already been 'demonstrated' in an animal model. The use of such therapies in Parkinson's disease is currently under investigation, using human stem cells. Moreover, human studies have already shown that transplantation of MSCs resulted in clinical improvement (24-32).

In conclusion, there is strong evidence to suggest that the aims of the project licence application are largely repetitive of previous studies and, in addition, have already been superceded by human studies. I refer you to the phase I and phase II studies involving stem cell transplants in human patients (33-37). Taking into consideration the fact that a 'substantial' severity banding was allocated to the procedure in question, the Home Office should have been more circumspect in requesting evidence from the project licence applicant, that non-animal methods had indeed been considered.

Based on the aforementioned excerpts from the FOIA documents, and an in-depth survey of the scientific literature, is it not conceivable that the Home Office project licence was granted contrary to paragraph 5 (a) of the Animals (Scientific Procedures) Act 1986, which states that 'The Secretary of State shall not grant a project licence unless he is satisfied that the purpose of the programme to be specified in the licence cannot be achieved satisfactorily by any other reasonably practicable method not entailing the use of protected animals'?.

I would welcome your feedback.

Yours sincerely,

Andre Menache MRCVS

References

1. Synchronized Neuronal Discharge in the Basal Ganglia of Parkinsonian Patients Is Limited to Oscillatory Activity Ron Levy, William D. Hutchison, Andres M. Lozano, and Jonathan O. Dostrovsky. J Neurosci. 2002 Apr 1;22(7):2855-61.
2. Neuroreport. 16(17):1877-1881, November 28, 2005. Mazzone, Paolo a; Lozano, Andres e; Stanzione, Paolo b c; Galati, Salvatore c; Scarnati, Eugenio d; Peppe, Antonella c; Stefani, Alessandro b c Implantation of human pedunculopontine nucleus: a safe and clinically relevant target in Parkinson's disease
3. www.patentstorm.us/patents/6356784-description.html
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25. http://www.tauac.org/site/News2?abbr=record_&page=NewsArticle&id=5180
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27. Kan I et al. J Comp Neurol. 2003 Jun 23;461(2):250-61. Dopaminergic differentiation of human mesenchymal stem cells--utilization of bioassay for tyrosine hydroxylase expression.
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29. Salvatore MF et al. Point source concentration of GDNF may explain failure of phase II clinical trial. Exp Neurol. 2006 Dec;202(2):497-505. Epub 2006 Sep 7.
30. Kan I, Melamed E, Offen D. : Handb Exp Pharmacol. 2007;(180):219-42. Autotransplantation of bone marrow-derived stem cells as a therapy for neurodegenerative diseases
31. Oiwa Y et al. Histological effects of intraputaminal infusion of glial cell line-derived neurotrophic factor in Parkinson disease model macaque monkeys. Neurol Med Chir (Tokyo). 2006 Jun;46(6):267-75; discussion 275-6.
32. Isakova IA et al. Preclinical evaluation of adult stem cell engraftment and toxicity in the CNS of rhesus macaques. Mol Ther. 2006 Jun;13(6):1173-84. Epub 2006 Feb 21.
33. Levesque M and Neuman T, "Autologous transplantation of adult human neural stem cells and differentiated dopaminergic neurons for Parkinson disease: 1-year postoperative clinical and functional metabolic result," American Association of Neurological Surgeons annual meeting, Abstract #702, April 8, 2002. Testimony of Dr. Michel Levesque, delivered at a hearing held by the United States Senate Subcommittee on Science, Technology, and Space on July 14, 2004. Accessed at: http://commerce.senate.gov/hearings/testimony.cfm?id=1268andwit_id=3670
34. Testimony of Mr. Dennis Turner, delivered at a hearing held by the United States Senate Subcommittee on Science, Technology, and Space on July 14, 2004. Accessed at: http://commerce.senate.gov/hearings/testimony.cfm?id=1268andwit_id=3676
35. Gill SS et al., "Direct brain infusion of glial cell line-derived neurotrophic factor in Parkinson disease," Nature Medicine 9 (May 2003) 589-595.
36. Clinical Trial Suggests Bone Marrow Stem Cells Are Useful For Spinal Cord Injury; Primecell Therapeutics Provided Pre-Clinical Study http://www.medicalnewstoday.com/articles/75758.php
37. Safety of Autologous Stem Cell Treatment for Traumatic Brain Injury in Children. This study is currently recruiting patients. Verified by The University of Texas Health Science Center, Houston May 2007. ClinicalTrials.gov Identifier: NCT00254722.

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