Animal Rights

Animal Research: Connecting the Dots

| by darioringach

 

Abnormal blood-vessel growth underlies many pathologies.  For example, it has long been known that blood formation proliferates during the expansion of cancerous tumors.  In studying retinal blood vessels of animals and humans, Isaac Michaelson postulated that diffusible substances stimulate their growth.  The race for the identification of such molecules began.

 

Today, sixty years after the initial studies by Michaleson, the Lasker prize in Clinical Medical Research goes to Napoleone Ferrara for the discovery of Vascular Endothelial Growth Factor (VEGF) as one of the major mediators of angiogenesis.  This work, and that of his many colleagues, is providing therapies for a number of vascular diseases.

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Let me connect the dots for you.

 

VEGF was first shown to correlated with the proliferation of blood-vessel cells in cultures and then it shown to correlate with blood-vessel growth in rats in-vivo.  They showed that VEGF was indeed the factor driving vascularization growth using knock-out mice.  This is called basic research.

 

From these initial studies in animals they asked: could it be that VEGF is responsible for some diseases involving abnormal growth of blood-vessels in humans?   This is called a hypothesis.

 

When he and his collaborators analyzed fluid from the eyes of normal and diseased human patients they found that, in fact, VEGF correlated with all those conditions that involved abnormal formation of blood vessels.   These are called supporting studies in humans.

 

These results looked promising and led to the idea that inhibiting VEGF could help treat such eye conditions.  This is a new hypothesis derived from prior research, or progress.

 

To test the idea they inhibited VEGF in the eyes of young mice with the disease.  They found that, as they had predicted, new blood-vessel formation was decreased.   His team then went on to show the same was true in adult animals.   This had developed a model of disease and its treatment.

 

To assist in the development of therapy with humans scientists developed a primate model of retinopathy.  First, they showed that, as predicted, injection of VEGF in primates produces retinopathy and other diseases related to abnormal blood formation.   This is called validation.

 

Then, they tested if, as one might have expected from the mouse model, inhibition of VEGF will prevent neo-vascularization in the primate.  It did.

 

 

With these advances Ferrara and collaborators then developed the anti-VEGF antibody (Ranibizumab) for use in human retinas.  This is called drug development.

 

Human clinical trials began in 2000.  The results were rather amazing.  While the untreated group steadily lost vision over the course of 2 years of the trial, the treatment not only stopped the deterioration of vision but actually improved it substantially.   This is called a medical breakthrough.

 

We connected the dots.

 

From basic research, to the development of mice and primate models of retinopathy, human studies, drug development, clinical trials and today the many benefits it brings to the patients.   This is how science works.

 

Opponents of such research cannot ignore these facts.  

 

Well, of course they can.  They actually do.  They shouldn’t.

 

Willful ignorance is simply not acceptable if we are to have an honest debate about the use of animals in research.

 

References:

 

Michaelson IC. Retinal circulation in man and animals. Springfield:Thomas,1954.

 

Ferrara N, Gerber HP, LeCouter J. The biology of VEGF and its receptors. Nat Med. 2003 Jun;9(6):669-76. Review. PubMed PMID: 12778165.

 

Adamis AP, Miller JW, Bernal MT, D'Amico DJ, Folkman J, Yeo TK, Yeo KT.

Increased vascular endothelial growth factor levels in the vitreous of eyes with proliferative diabetic retinopathy. Am J Ophthalmol. 1994 Oct 15;118(4):445-50.

 

Frank RN. Treating diabetic retinopathy by inhibiting growth factor pathways.  Curr Opin Investig Drugs. 2009 Apr;10(4):327-35. Review. 

 

Miller JW, Adamis AP, Shima DT, D'Amore PA, Moulton RS, O'Reilly MS, Folkman J, Dvorak HF, Brown LF, Berse B, et al. Vascular endothelial growth

factor/vascular permeability factor is temporally and spatially correlated with ocular angiogenesis in a primate model. Am J Pathol. 1994 Sep;145(3):574-84. PubMed PMID: 7521577; PubMed Central PMCID: PMC1890317.

 

Adamis AP, Shima DT, Tolentino MJ, Gragoudas ES, Ferrara N, Folkman J, D'Amore PA, Miller JW. Inhibition of vascular endothelial growth factor prevents retinal ischemia-associated iris neovascularization in a nonhuman primate. Arch Ophthalmol. 1996 Jan;114(1):66-71. PubMed PMID: 8540853.

 

Aiello LP, Avery RL, Arrigg PG, Keyt BA, Jampel HD, Shah ST, Pasquale LR,

Thieme H, Iwamoto MA, Park JE, et al. Vascular endothelial growth factor in

ocular fluid of patients with diabetic retinopathy and other retinal disorders. N Engl J Med. 1994 Dec 1;331(22):1480-7. PubMed PMID: 7526212.

 

Diabetic Retinopathy Clinical Research Network, Elman MJ, Aiello LP, Beck RW, Bressler NM, Bressler SB, Edwards AR, Ferris FL 3rd, Friedman SM, Glassman AR, Miller KM, Scott IU, Stockdale CR, Sun JK. Randomized trial evaluating ranibizumab plus prompt or deferred laser or triamcinolone plus prompt laser for  diabetic macular edema. Ophthalmology. 2010 Jun;117(6):1064-1077.e35. Epub 2010 Apr 28. PubMed PMID: 20427088; PubMed Central PMCID: PMC2937272.

 

Tolentino MJ, Miller JW, Gragoudas ES, Jakobiec FA, Flynn E, Chatzistefanou K, Ferrara N, Adamis AP. Intravitreous injections of vascular endothelial growth factor produce retinal ischemia and microangiopathy in an adult primate. Ophthalmology. 1996 Nov;103(11):1820-8. PubMed PMID: 8942877.