R&D&i

Ebiotec’s Research & Development & innovation department endeavors to answer a wide range of questions on:

  • how the different components of the nervous system are organized in degenerative disorders
  • how certain active ingredients act against tumoral diseases
  • what the therapeutic effects of the nutraceuticals developed are

These questions are pieces of a jigsaw which slowly but surely fit together due to the combined application of analytical tools in the fields of genetics, molecular biology, neuroanatomy, electrophysiology, pharmacology, behavioral biology and neuroimaging, all of which are present in our preclinical research departments. The R&D&i department consists of a highly-qualified multidisciplinary team, formed mainly of expert researchers in biology, pharmacy and medicine. This biomedical team is complemented by specialists in different fields of applied experimental science from associated companies, and national and international universities.

 

The Neurosciences department carries out its activity in experimental histopathological studies of prevalent diseases in in vivo and in vitro models.
Neurodegenerative Diseases (Alzheimer’s and Parkinson’s)
Tumoral Diseases (Colorectal cancer)
Cerebro-Cardiovascular Diseases (Ictus)

Our R&D&i services::

  • Development of preclinical tests in animal models for the projects of biotechnology companies and external laboratories.
  • Development of animal models of different pathologies for preclinical experimentation
  • Development and analysis of experimental tests for preclinical application:
    • Laboratory processing of animal tissue samples.
    • Application of molecular biology techniques (Immunohistochemistry/fluorescence, neuroimaging, etc.)
    • Expert opinion and analysis of experimental results in experimental animal models

 

 

The Biotechnology department carries out its activity in the characterization of new nutraceutical products and functional foods of marine and vegetable origin, seeking to improve bioavailability and bioactivity markers and to reduce the risk of contracting diseases, by acting upon the nutrigenomic profiles (genetic and epigenetic risk factors) possibly involved in prevalent pathologies.
Our R&D&i services:
– Explore biotechnological products derived from ingredients of marine and vegetable origin
– Study their bioactive properties
– Characterize the preventive-therapeutic profile of bioproducts against prevalent diseases

The activity of the Genetics department includes the performance of proteomics and genetic expression studies.

Our R&D&i services:

    • Proteomics has a huge potential in the field of biomedicine:

– Developing methods of early diagnosis
– Designing alternative therapies
– Identifying target proteins
– Developing drugs
– Performing pathogenesis studies.

    • Gene expression has the following biomedical applications:

– Comparison of gene expression between healthy and pathological tissues (monitoring the degenerative process).
– Analysis of the biological disruptions caused by chemical products, medicines, nutraceuticals, toxins, mutagens or dietary compounds.
– Molecular characterization of the effect of biologically active substances.
– Assessment of the toxicity and effect of a drug by analysis of the changes in gene expression during its administration period.

Encapsulation of bioactive compounds in liposomes: This consists of the encapsulation of a particular protein in a vesicle formed by a lipid liposome (a biologically active sphingolipid) with regenerative, anti-inflammatory and neuronal properties, thus comprising an innovative form for the administration of DRUGS, NUTRACEUTICALS and BIOPRODUCTS. They present high biocompatibility, biodegradability and an absence of biotoxicity..

Lines of research

 

Neurodegenerative Diseases

Principal lines of research
Neurodegenerative diseases provide an extremely useful pathological model of gradual progression for the study of neuronal dysfunction and its symptomatic repercussions over time. In our laboratory we analyze these neuropathological markers in experimental models of Alzheimer’s disease in order to characterize how they affect the progressive neuronal dysfunction over time, and how they differ from the neuronal deterioration due to aging.
The principal project currently under way is:

Development of the EB-101 (EE-AD-S1P) vaccine against Alzheimer’s disease.

Objective: Identification of the neuronal dysfunction in the hippocampus of animal models of Alzheimer’s disease.
To carry out this project, we have based our analytical tools on various fields of molecular biology: Neuromorphology, Neuroplasticity, Neuroimaging, Genomics, Proteomics and Biochemistry.

In vivo/in vitro studies of carcinogenic pathologies

The purpose of animal (in vivo) and cellular (in vitro) experimental models is to reproduce a pathological effect in order to clarify preclinically applicable biological phenomena. In our laboratory we analyze the therapeutic effects of various marketable products in experimental models of cancer and their efficacy in physiological, biochemical and behavioral terms. In cooperation with the Genetics and Biotechnology departments, we perform toxicity, histopathology and genetic profile studies in animal models of tumoral pathology. Additionally, studies are carried out on the therapeutic efficacy of products with possible therapeutic activity in specific animal models.

Screening of nutraceutical products

Our department provides the scientific backing for the research and development of innovative nutraceuticals of marine and vegetable origin for their subsequent marketing. Each nutraceutical is tested both in vitro and in vivo in order to characterize its bioactive efficacy against a particular biological profile, thus to produce a product with scientifically proven beneficial intrinsic bioactive characteristics.
The purpose of animal (in vivo) and cellular (in vitro) experimental models is to reproduce a pathological effect in order to clarify preclinically applicable biological phenomena. In our laboratory we analyze the therapeutic effects of various marketable products in experimental models of cancer and their efficacy in physiological, biochemical and behavioral terms. In cooperation with the Genetics and Biotechnology departments, we perform toxicity, histopathology and genetic profile studies in animal models of tumoral pathology. Additionally, studies are carried out on the therapeutic efficacy of products with possible therapeutic activity in specific animal models.
The principal project currently under way is:

Development of nutraceuticals of marine and vegetable origin, to fight prevalent diseases.

Objective: Preclinical characterization (in vitro and in vivo) of natural extracts applied to prevalent pathologies, by means of cellular and animal models.

Development process:

Ebiotec’s efforts in bioprospecting yield as a result the continued discovery and development of new compounds with bioactive activity, which will prove their therapeutic effect in preclinical tests. These tests entail two experimental phases:

  1. Exploration phase: “Primary screening”, during which a possible functional compound is discovered, and a Proof of Concept is established by studies in standardized cell cultures (in vitro).
  2. Confirmation phase: “Secondary or specific screening”, during which the effect of this bioactive compound on a particular disease is analyzed by the experimental design of a study in animal models (in vivo).

Efficacy and toxicity of DRUGS, NUTRACEUTICALS and BIOPRODUCTS

Ebiotec’s preclinical research team develops the best system for the testing of the efficacy and toxicity of DRUGS, NUTRACEUTICALS and BIOPRODUCTS in cellular and animal models of different pathologies, excellent models for the testing of the safety and efficacy of the new drugs which are designed or developed.

Gene expression analysis

 

1. Extraction of RNA with commercial kits based on filtration through columns of silica.
2. Assessment of the concentration and purity of the RNA by spectrophotometry.
3. Determination of the expression pattern of a particular gene using real-time PCR and Taqman probes (absolute and relative quantification).
4. Analysis and interpretation of data by standard curves or ΔΔCT method.

1. Comparison of the gene expression between healthy and diseased tissues, monitoring the pathological or disease process.
2. Analysis of the biological disruptions caused by chemical products, medicines, nutraceuticals, toxins, mutagens or dietary compounds.
3. Molecular characterization of the effect of biologically active substances.
4. Assessment of the toxicity and effect of a drug by analysis of the changes in gene expression during its administration period.

1. Humans (mononuclear peripheral blood cells, and other cell types)
2. Cells in culture and in laboratory animals

Scientific Publications

 

Publications

Cacabelos, R. Psychogeriatric research: A conceptual introduction to aging and geriatric neuroscience. Psychogeriatrics, 1:158-188 (2001).
Allison, A.C., Cacabelos, R., Lombardi, V.R.M., Álvarez, X.A., Vigo, C. Celastrol, a potent antioxidant and anti-inflammatory drug, as a possible treatment for Alzheimer’s disease. Prog. Neuro-Psychopharmacol. Biol. Psychiat., 25:1341-1357 (2001).
Cacabelos, R., Santamaría, J.L. Hipertensión y Demencia. Mecanismos etiopatogénicos y factores genéticos. Hipertensión Clínica, IV/3:626-659 (2001).
Fernández-Novoa, L., Cacabelos, R. Histamine function in brain disorders. Behav. Brain Res., 124:213-233 (2001). Cacabelos, R. Enfermedad de Alzheimer. Presente terapéutico y retos futuros (I). Rev. Colomb. Psiquiatría, XXX/3:215-238 (2001).
Cacabelos, R. Enfermedad de Alzheimer. Presente terapéutico y retos futuros (II). Rev. Colomb. Psiquiatría, XXX/4:323-350 (2001).
Lombardi, V.R.M., Cagiao, A., Fernández-Novoa, L., Álvarez, X.A., Corzo, M.D., Zas, R., Sampedro, C., Cacabelos, R. Short term food supplementation effects of a fish derived extract on the immunological status of pregnant rats and their sucking pups. Nutrition Res., 21:1425-1434 (2001).

Cacabelos, R. Pharmacogenomics in Alzheimer’s disease. Min. Rev. Medic. Chem., 2:59-84 (2002).

Cacabelos, R. Pharmacogenomics for the treatment of dementia. Ann. Med., 34:357-379 (2002).

Lombardi, V.R.M., Fernández-Novoa, L., Corzo, D., Zas, R., Cacabelos, R. Enhancement in immune function and growth using E-JUR-94013 supplementation. Meth. Find. Exp. Clin. Pharmacol., 24:573-578 (2002).

Miguel-Hidalgo, J.J., Álvarez, X.A., Cacabelos, R., Quack, G. Neuroprotection by memantine against neurodegeneration induced by beta-amyloid(1-40). Brain Res., 958:210-221 (2002).

Cacabelos, R. The histamine-citokine network in Alzheimer disease: Etiopathogenic and pharmacogenomic implications. In: Mapping the Progress of Alzheimer’s and Parkinson’s Disease. Mizuno, Y., Fisher, A., Hanin, I. (Eds.). Advances in Behavioral Biology, 51:59-64 (2002).

Takeda, M., Cacabelos, R., Ray, O., Förstl, H., Hoon Oh, B. International perspective on the diagnosis and treatment of dementia. Cognition & Dementia, 2:53-63 (2003).
Takeda, M., Okochi, M., Sugaya, K., De-Maw, C., Hashimoto, R., Kuroda, S., Shinosaka, K., Kudo, T., Tanaka, T., Cacabelos, R. Research strategy for understanding neuronal plasticity and degeneration. Seishin Shinkeigaku Zasshi, 105:43-46 (2003).
Cacabelos, R., Fernández-Novoa, L., Lombardi, V., Takeda, M. Genetic variation and pharmacogenomics in Alzheimer disease. Psychiat. Neurol. Jap., 105:47-67 (2003).
Lombardi, V.R.M., Etcheverría, I., Fernández-Novoa, L., Cacabelos, R. In vitro regulation of rat-derived microglia. Neurotox. Res., 5:201-212 (2003).
Lombardi, V.R.M., Etcheverría, I., Fernández-Novoa, L., Blanco, A., Díaz, J., Cacabelos, R. Extracts from Polypodium ferns upregulate the expression of CD95 in human peripheral blood lymphocytes. Orient. Pharm. Exper. Med., 3:90-99 (2003).
Álvarez, X.A., Sampedro, C., Pérez, P., Laredo, M., Couceiro, V., Hernández, A., Figueroa, J., Varela, M., Arias, D., Corzo, L., Zas, R., Lombardi, V., Fernández-Novoa, L., Pichel, V., Cacabelos, R., Windisch, M., Aleixandre, M., Moessler, H. Positive effects of cerebrolysin on electroencephalogram slowing, cognition and clinical outcome in patients with postacute traumatic brain injury: an exploratory study. Intern. Clin. Psychopharmacol., 18:271-278 (2003).
Cacabelos, R. The application of functional genomics to Alzheimer’s disease. Pharmacogenomics, 4:597-621 (2003).

Isaza, C., Henao, J., López, A.M., Cacabelos, R. Allelic variants of the thiopurine methyltransferase (TPMT) gene in the Colombian population. Meth. Find. Exp. Clin. Pharmacol., 25:423-429 (2003).
Cacabelos, R., Fernández-Novoa, L., Lombardi, V., Corzo, L., Pichel, V., Kubota, Y. Cerebrovascular risk factors in Alzheimer’s disease: Brain hemodynamics and pharmacogenomic implications. Neurol. Res., 25:567-580 (2003).
Lombardi, V.R.M., Fernández-Novoa, L., Cacabelos, R. Neuroglia and neurotrophic factors (NTFs): potential targets for future therapeutics. Current Topics in Pharmacology, 7:229-246 (2003).

Pichel, V., Etcheverría, I., Amado, L., Kubota, Y., Cacabelos, R. Cerebrovascular risk factors and brain hemodynamics in dementia. In: Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, pp. 23-27 (2003).
Lombardi, V.R.M., Amado, L., Fernández-Novoa, L., Etcheverría, I., Seoane, S., Cacabelos, R. Flow cytometry analysis of CD28-/CD8+ suppressor cell precursor and CD45RO+/CD4+ memory T lymphocytes in the peripheral blood of Alzheimer’s disease patients. In: Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, pp. 57-61 (2003).
Corzo, L., Zas, R., Fernández-Novoa, L., Cacabelos, R. SERUM nitric oxide in Alzheimer disease. In: Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, pp. 63-68 (2003).
Kubota, Y., Pichel, V., Fernández-Novoa, L., Cacabelos, R. Combination therapy in Alzheimer disease: a pharmacogenomic study. In: Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, pp. 87-90 (2003).

Etcheverría, I., Pichel, V., Amado, L., Fernández-Novoa, L., Lombardi, V., Cacabelos, R. APOE genotype-related brain atrophy in the Spanish population. In: Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, pp. 91-96 (2003).
Fernández-Novoa, L., Lombardi, V.R.M., Seoane, S., Etcheverría, I., Corzo, L., Cacabelos, R. The ACE gene in Alzheimer’s disease. In: Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, pp. 123-126 (2003).

Cacabelos, R., Vallejo, A.I., Lombardi, V., Fernández-Novoa, L., Pichel, V. E-SAR-94010 (LipoEsar®): A pleiotropic lipoprotein compound with powerful anti-atheromatous and lipid lowering effects. CNS Drug Rev., 10:200-201 (2004).
Cacabelos, R., Fernández-Novoa, L., Corzo, L., Pichel, V., Lombardi, V., Kubota, Y. Genomics and phenotypic profiles in dementia: Implications for pharmacological treatment. Meth. Find. Exp. Clin. Pharmacol., 26:421-444 (2004).
Cacabelos, R., Fernández-Novoa, L., Corzo, L., Amado, L., Pichel, V., Lombardi, V., Kubota, Y. Phenotypic profiles and functional genomics in Alzheimer’s disease and in dementia with a vascular component. Neurol. Res., 26:459-480 (2004).
Cacabelos, R. Genomic characterization of Alzheimer’s disease and genotype-related phenotypic analysis of biological markers in dementia. Pharmacogenomics, 5:1049-1105 (2004).
Cacabelos, R., Fernández-Novoa, L., Pichel, V., Lombardi, V., Kubota, Y., Takeda, M. Pharmacogenomic studies with a combination therapy in Alzheimer’s disease. In: Molecular Neurobiology of Alzheimer’s Disease and Related Disorders. Takeda, M., Tanaka, T., Cacabelos, R. (Eds.). Karger, Basel, pp. 94-107 (2004).
Cacabelos, R., Lombardi, V., Fernández-Novoa, L., Kubota, Y., Corzo, L., Pichel, V., Takeda, M. A functional genomics approach to the analysis of biological markers in Alzheimer disease. In: Molecular Neurobiology of Alzheimer’s Disease and Related Disorders. Takeda, M., Tanaka, T., Cacabelos, R. (Eds.). Karger, Basel, pp. 236-285 (2004).

Isaza, C., Henao, J., Ramírez, E., Cuesta, F., Cacabelos, R. Polymorphic variants of the beta-2-adrenergic receptor (ADRB2) gene and ADRB2-related propanolol-induced dyslipidemia in the Colombian population. Meth. Find. Exp. Clin. Pharmacol., 27:237-244 (2005).
Cacabelos, R. Función cerebrovascular en la enfermedad de Alzheimer (2005).
Lombardi, V.R.M., Fernández-Novoa, L., Etcheverría, I., Seoane, S., Cacabelos, R. Effects of fish-derived lipoprotein extracts on activation markers, Fas expression and apoptosis in peripheral blood lymphocytes. Intern. Immunopharmacol., 5:253-262 (2005).
Cacabelos, R., Kubota, Y., Isaza, C., Henao, J., Fernández-Novoa, L., Lombardi, V.R.M., Corzo, L., Pichel, V. Functional genomics and pharmacogenetics in Alzheimer’s disease. In: Recent Progress in Alzheimer’s and Parkinson’s Diseases. Hanin, I., Cacabelos, R., Fisher, A. (Eds.). Taylor & Francis, London, pp. 89-102 (2005).
Lombardi, V.R.M., Fernández-Novoa, L., Etcheverría, I., Seoane, S., Cacabelos, R. Regulating factors for microglial activation: implication for Alzheimer’s disease and brain damage. In: Recent Progress in Alzheimer’s and Parkinson’s Diseases. Hanin, I., Cacabelos, R., Fisher, A. (Eds.). Taylor & Francis, London, pp. 171-176 (2005).
Cacabelos, R., Fernández-Novoa, L., Lombardi, V., Kubota, Y., Takeda, M. Molecular genetics of Alzheimer’s disease and aging. Meth. Find. Exp. Clin. Pharmacol., 27(Suppl. A):1-573 (2005).

Cacabelos, R. Pharmacogenomics, nutrigenomics and therapeutic optimization in Alzheimer’s disease. Aging Health, 1:303-348 (2005).
Cacabelos, R. Pharmacogenomics and therapeutic prospects in Alzheimer’s disease. Expert Opin. Pharmacother., 6:1967-1987 (2005).
Cacabelos, R. Role of nutrition in the prevention of Alzheimer’s disease. Aging Health, 1:359-362 (2005).
Álvarez, X.A., Corzo, L., Laredo, M., Sampedro, C., Cacabelos, R., Windisch, M., Moessler, H., Crook, T.H. Neuropeptide dietary supplement N-PEP-12 enhances cognitive function and activates brain bioelectrical activity in healthy elderly subjects. Meth. Find. Exper. Clin. Pharmacol., 27:493-487 (2005).

Cacabelos, R. Homocysteine and cognition: from Galenic dogmatism to genetic relativism. Aging Health, 2:783-786 (2006).
Álvarez, X.A., Cacabelos, R., Laredo, M., Couceiro, V., Sampedro, C., Varela, M., Corzo, L., Fernández-Novoa, L., Vargas, M., Aleixandre, M., Linares, C., Granizo, E., Muresanu, D., Moessler, H. A 24-week, double-blind, placebo-controlled study of three dosages of Cerebrolysin in patients with mild to moderate Alzheimer’s disease. Eur. J. Neurol., 13:43-54 (2006).
Cacabelos, R., Takeda, M. Pharmacogenomics, nutrigenomics and future therapeutics in Alzheimer’s disease. Drugs Future, 31(Suppl. B):5-146 (2006).

Cacabelos, R. Molecular pathology and pharmacogenomics in Alzheimer’s disease: Polygenic-related effects of multifactorial treatments on cognition, anxiety, and depression. Meth. Find. Exper. Clin. Pharmacol., 29(Supp. A):1-91 (2007).
Takeda, M., Cacabelos, R. (Eds.). Alzheimer’s disease genomics. Cognition and Dementia, 6(Suppl.):7-113 (2007).
Cacabelos, R. Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. Neuropsychiat. Dis. Treat., 3:303-333 (2007).
Álvarez, A., Cacabelos, R., Sampedro, C., García-Fantini, M., Aleixandre, M. Serum TNF-alpha levels are increased and correlate negatively with free IGF-1 in Alzheimer’s disease. Neurobiol. Aging, 28:533-536 (2007).
Corzo, L., Zas, R., Rodríguez, S., Fernández-Novoa, L., Cacabelos, R. Decreased levels of serum nitric oxide in different forms of dementia. Neurosci. Lett., 420:263-267 (2007).
Cacabelos, R (Ed.). Cholinesterase inhibitors in Dementia. Ten years of Donepezil in Alzheimer’s Disease and CNS Disorders (1996-2006): Therapeutic Assessment and Pharmacogenetics. Gen-T/The EuroEspes Journal, Suppl. 1:1-52 (2007).
Cacabelos, R., Llovo, R., Fraile, C., Fernández-Novoa, L. Pharmacogenetic aspects of therapy with cholinesterase inhibitors: The role of CYP2D6 in Alzheimer’s disease pharmacogenetics. Cur. Alzheimer Res., 4:479-500 (2007).
Cacabelos, R. Pharmacogenetic basis for therapeutic optimization in Alzheimer’s disease. Mol. Diag. Ther., 11:385-405 (2007).
Takeda, M., Cacabelos, R., Ray, O., Förstl, H., Hoon Oh, B. Dementia in the World. Cogn. Dementia, 2:53-63 (2007).

Harguindey, S., Orive, G., Cacabelos, R., Meléndez Hevia, E., Díaz de Otazu, R., Arranz, J.L., Anitua, E. An integral approach to the etiopathogenesis of human neurodegenerative diseases (HNDDs) and cancer. Possible therapeutic consequences within the frame of the trophic factor withdrawal syndrome (TFWS). Neuropsychiat. Dis. Treat., 4:1073-1087 (2008).
Cacabelos, R. Application of nutrigenomics to Alzheimer’s disease. AgroFood, 19:37-40 (2008). Cacabelos, R. Pharmacogenomics and therapeutic prospects in dementia. Eur. Arch. Psychiatry Clin. Neurosci., 258(Suppl. 1):28-47 (2008).
Cacabelos, R. Influence of pharmacogenetic factors on Alzheimer’s disease therapeutics. Neurodegenerative Dis., 5:176-178 (2008).
Cacabelos, R. Pharmacogenomics in Alzheimer’s disease. Meth Mol. Biol., 448:213-357 (2008). Cacabelos, R. Pharmacogenomics in Alzheimer’s disease. In: Pharmacogenomics and Personalized Medicine. Cohen, N. (Ed.). pp. 317-368 (2008).
Cacabelos, R. Pleiotropic effects of Apolipoprotein E in dementia: Influence on functional genomics and pharmacogenetics. Adv. Behav. Biol., 57:355-367 (2008).
Álvarez, X.A., Sampedro, C., Figueroa, J., Tellado, I., González, A., García-Fantini, M., Cacabelos, R., Muresanu, D., Moessler, H. Reductions in qEEG slowing over 1 year and after treatment with cerebrolysin in patients with moderate-severe traumatic brain injury. J. Neural Transm., 115:683-692 (2008).

Álvarez, X.A., Sampedro, C., Cacabelos, R., Linares, C., Aleixandre, M., García-Fantini, M., Moessler, H. Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer’s disease patients treated with the neurotrophic agent Cerebrolysin. Int. J. Neuropsychopharmacol., 12:867-872 (2009).

Cacabelos, R. Pharmacogenomic Biomarkers in Neuropsychiatry: The Path to Personalized Medicine in Mental Disorders. In: The Handbook of Neuropsychiatric Biomarkers, Endophenotypes and Genes. Vol. IV: Molecular Genetic and Genomic Markers. Ritsner, M.S. (Ed.). Springer, pp. 3-63 (2009).

Cacabelos, R., Martínez-Bouza, R., Fernández-Novoa, L., Carril, J.C., Llovo, R., Tellado, I., Corzo, L., Fraile, C., Cacabelos, N., Bello, A., McKay, A., Bermo, A., Carrera, I., Álvarez, A., Lombardi, V. Personalized medicine of dementia. Pharmacogenomics of Alzheimer’s disease. Gen-T/The EuroEspes Journal, 4:18-48 (2009).
Lombardi, V.R.M., Martínez, E., Chacon, R., Etcheverría, I., Cacabelos, R. Effects of FR-91 on human tumor cell lines. Gen-T/The EuroEspes Journal, 4:50-60 (2009).
Cacabelos, R. Pharmacogenomics and therapeutic strategies for dementia. Expert Rev. Mol. Diag., 9:567-611 (2009).
Lombardi, V.R.M., Martínez, E., Chacón, R., Etcheverría, I., Cacabelos, R. Effects of FR-91 on immune cells from healthy individuals and from patients with non-Hodgkin lymphoma. J. Biomed. Biotech., DOI: 10.1155/2009/187015 (2009).

Cacabelos, R. Pharmacogenomic protocols in CNS disorders and dementia. Neurodegenerative Dis., 7:167-169 (2010).
Cacabelos, R., Martínez-Bouza, R. Genomics and pharmacogenomics of schizophrenia. CNS Neuroscience & Therapeutics. DOI: 10.111_j.1755-5949.2010.00187.
Cacabelos, R., Martínez-Bouza, R. Genomics and pharmacogenomics of dementia. CNS Neurosciences & Therapeutics. DOI: 10.111_j.1755-5949.2010.00189.
Cacabelos, R., Fernández-Novoa, L., Martínez-Bouza, R., McKay, A., Carril, J.C., Lombardi, V., Corzo, L., Carrera, I., Tellado, I., Nebril, L., Alcaraz, M., Rodríguez, S., Casas, A., Couceiro, V., Alvarez, A. Future trends in the pharmacogenomics of brain disorders and dementia: Influence of APOE and CYP2D6 variants. Pharmaceuticals 3:3040-3100 (2010); doi: 10.3390/ph3103040.
Cacabelos, R., Martínez-Bouza, R., Carril, J.C., Fernández-Novoa, L., Llovo, R., Carrera, I., Corzo, L., Fraile, C., Telladi, I., McKay, A., Bello, A., Cacabelos, N., Lombardi, V. Tarjeta Farmacogenética EuroEspes: La personalización del tratamiento farmacológico. Gen-T 5:36-60 (2010).

Cacabelos, R., Fernández-Novoa, L., Martínez-Bouza, R., Carril, R., Carrera, I., Fraile, C., Tellado, I., Corzo, L., Lombardi, V. Los genes de la locura. Genómica de la esquizofrenia y los trastornos psicóticos. Gen-T 6:34-57 (2010).
Takeda, M., Martínez, R., Kudo, T., Tanaka, T., Okochi, M., Tagami, S., Morihara, T., Hashimoto, R., Cacabelos, R. Apolipoprotein E and central nervous system disorders: Reviews of clinical findings. Psychiat Clin Neurosci 64:592-607 (2010).
Lombardi, V.R.M., Cacabelos, R. Neuron-Glia interactions and neurodegeneration. Psychogeriatria Polska 7(4):115-130 (2010).

Cacabelos, R. Genomics of psychosis. Gen-T (EuroEspes J Int Ed) 3:3 (2011).
Cacabelos, R., Fernández-Novoa, L., Lombardi, V., Carril, J.C., Corzo, L., Carrera, I., Tellado, I., Martínez, R., McKay, A., Takeda, M. Genomics of schizophrenia and psychotic disorders. Gen-T (EuroEspes J Int Ed) 3:6-86 (2011).
Carril, J.C., Martínez-Bouza, R., Fernández-Novoa, L., Carrera, I., Corzo, L., Fraile, C., Tellado, I., McKay, A., Bello, A., Lombardi, V., Cacabelos, R. The EuroEspes Pharmacogenetic Card. Personalization of pharmacological treatment. Gen-T (EuroEspes J Int Ed) 3:88-118 (2011).
Carrera, I., Lombardi, V.R.M., Etcheverría, I., Martínez, E., Chacón, R., Cacabelos, R. Prevención de colitis experimental crónica inducida por dextrán sulfato sódico (DSS) en ratones tratados con FR-91. Gen-T 7:19-30 (2011).
Cacabelos, R., Martínez-Bouza, R., Tellado, I., Alcaraz, M., Nebril, L., Casas, A., González, Y., López, L., Couceiro, V., Fraile, C., Rodríguez, S., Corzo, L., Carril, J.C., Lombardi, V., Carrera, I., Fernández-Novoa, L. Gen-T 7:42-74 (2011).
Carrera, I., Etcheverría, I., Fernández-Novoa, L., Lombardi, V., Vigo, C., Cacabelos, R. Desarrollo de la vacuna EuroEspes EB101 contra la enfermedad de Alzheimer. Gen-T 8: 38-52 (2011).
Cacabelos, R. Alzheimer’s disease 2011: Where are we heading. Gen-T 8:54-86 (2011).
Cacabelos, R. Pharmacogenomics of Alzheimer’s disease. Metabolomics 1:3, 1000106e (2011). http://dx.doi.org/10.4172/2153-0769.1000106e.
Alvarez, X.A., Cacabelos, R., Sampedro, C., Couceiro, V., Aleixandre, M., Vargas, M., Linares, C., Granizo, E., García-Fantini, M., Baurecht, W., Doppler, E., Moessler, H. Combination treatment in Alzheimer’s disease: Results of a randomized, controlled trial with cerebrolysin and donepezil. Cur Alzheimer Res 8:583-591 (2011).
Alvarez, X.A., Cacabelos, R., Sampedro, C., Aleixandre, M., Linares, C., Granizo, E., Doppler, E., Moessler, H. Efficacy and safety of cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized, doubled-blind, controlled trial investigating three dosages of cerebrolysin. Eur J Neurol 18:59-68 (2011).
Cacabelos, R., Hashimoto, R., Takeda, M. Pharmacogenomics of antipsychotics efficacy for schizophrenia. Psychiat Clin Neurosci 65:3-19 (2011).

Cacabelos, R., Martínez-Bouza, R., Carril, J.C., Fernández-Novoa, L., Lombardi, V., Carrera, I., Corzo, L., McKay, A. Genomics and pharmacogenomics of brain disorders. Current Pharmaceutical Biotechnology 13:674-725 (2012).
Lombardi, V.R.M., Etcheverría, I., Carrera, I., Cacabelos, R., Chacón, A. Prevention of chronic experimental colitis induced by dextran sulphate sodium (DSS) in mice treated with FR91. J. Biomed. Biotech., (2012). Doi:10.1155/2012/826178.
Cacabelos, R., Martínez, R., Fernández-Novoa, L., Carril, J.C., Lombardi, V., Carrera, I., Corzo, L., Tellado, I., Leszek, J., McKay, A., Takeda, M. Genomics of dementia: APOE- and CYP2D6-related pharmacogenetics. Intern. J. Alzheimer Dis., (2012). Doi:10.1155/2012/518901.
Carrera I., Etcheverría, I., Fernández-Novoa, L., Lombardi, V., Cacabelos, R., Vigo, C. Vaccine development to treat Alzheimer’s disease neuropathology in APP/PS1 transgenic mice. Intern. J. Alzheimer Dis., (2012). Doi:10.1155/2012/376138.
Canuet, L., Tellado, I., Couceiro, V., Fraile, C., Fernández-Novoa, L., Ishii, R., Takeda, M., Cacabelos, R. Resting-state network disruption and APOE genotype in Alzheimer’s disease: A lagged functional connectivity study. PLoS ONE (2012) 7(9): e46289. Doi:10.1371/journal.pone.0046289.

Cacabelos, R. Pharmacogenomics of central nervous system (CNS) drugs. Drug Development Research, 73:461-476 (2012).
Cacabelos, R. The metabolomics paradigm of pharmacogenomics in complex disorders. Metabolomics (2012), 2:5. http//dx.doi.org/10.4172/2153-0769.1000e119.
Aliev, G., Reddy, V.P., Cacabelos, R. Role of electron microscopy-immunocytochemistry and in situ hybridization in the study of oxidative stress-induced mitochondrial abnormalities and the pathobiology of neurodegeneration and cancer. In: Current Microscopy Contributions to Advances in Science and Technology. Méndez-Vilas, A. (Ed). pp. 366-385 (2012).

Cacabelos, R., Cacabelos, P., Aliev, G. Genomics and pharmacogenomics of antipsychotic drugs. Open J. Psychiatry 3:46-139 (2013). Doi:10.4236/ojpsych.2013.31008.
Romero, A., Cacabelos, R., Oset-Gasque, M.J., Samadi, A., Marco-Contelles, J. Novel tacrine-related drugs as potential candidates for the treatment of Alzheimer’s disease. Bioorganic & Medicinal Chemistry Lett., (2013). Doi: http://dx.doi.org/10.1016/j.bmcl.2013.02.017.
Carrera, I., Cacabelos, R. Novel immunotherapeutic procedures for prevention of Alzheimer’s disease. Drug Des., 2013, 2:2. http://dx.doi.org/10.4172/2169-0138.1000107.
Aliev, G., Obrenovich, M.E., Tabrez, S., Jabir, N.R., Reddy, V.P., Li, Y., Burnstock, G., Cacabelos, R., Kamal, M.A. Link between cancer and Alzheimer disease via oxidative stress induced by nitric oxide-dependent mitochondrial DNA overproliferation and deletion. Oxidative Medicine and Cellular Longevity (2013). http://dx.doi.org/10.1155/2013/962984.
Aliev, G., Palacios, H.H., Cacabelos, P., Cacabelos, R., Burzynski, G., Burzynski, S.R. Mitochondria specific antioxidants and their derivatives in the context of the drug development for neurodegeneration and cancer. Drug Des., (2013), 2:1. http://dx.doi.org/10.4172/2169-0138.1000103.

Carrera, I., Etcheverría, I., Li, Y., Fernández-Novoa, L., Lombardi, V., Vigo, C., Palacios, H.H., Benberin, V., Cacabelos, R., Aliev, G. Immunocytochemical characterization of Alzheimer disease hallmarks in APP/PS1 transgenic mice treated with a new anti-amyloid-β vaccine. BioMed Research International (2013). http://dx.doi.org/10.1155/2013/709145.
Torrellas, C., Fraile, C., Carril, J.C., Fernández-Novoa, L., Cacabelos, R. Importancia de la farmacogenética en el tratamiento de la hipertension arterial. Gen-T/The EuroEspes J., 9:15-30 (2013).
Corzo, L., Rodríguez, S., Lombardi, V., Alejo, R, Cacabelos, R. Propiedades biológicas de Mineraxin. Gen-T/The EuroEspes J., 9:31-40 (2013).
Romero, A., Cacabelos, R., Marco-Contelles, J. Derivados de tacrina contra la enfermedad de Alzheimer. Gen-T/The EuroEspes J., 9:57-64 (2013).
Canuet, L., Tellado, I., Couceiro, V., Fraile, C., Fernández-Novoa, L., Ishii, R., Takeda, M., Cacabelos, R. Influencia del genotipo APOE sobre la actividad cerebral en la enfermedad de Alzheimer. Gen-T/The EuroEspes J., 9:65-74 (2013).
Fernández-Novoa, L., Corzo, L., Seoane, S., Cacabelos, R. Histamina: una molécula polifacética. Gen-T/The EuroEspes J., 9:75-86 (2013).

Cacabelos, R. Primera Guía Mundial de Farmacogenómica. Del genoma humano a los retos futuros de la medicina genómica. Gen-T/The EuroEspes J., 9:89-114 (2013).

Carril, J.C., Seoane, S., Cacabelos, R. Utilidad de la familia de enzimas CYP3A4 como marcadores de interés en farmacogenética. Gen-T/The EuroEspes J., 9:115-124 (2013).
Tellado, I., Canuet, L., Cacabelos, R. Farmacogenómica de los agentes transportadores SLC. Gen-T/The EuroEspes J., 9:125-142 (2013).
Lombardi, V.R.M., Cacabelos, R. Nuevas dianas terapéuticas en la lucha contra el cancer. Gen-T/The EuroEspes J., 9:143-154 (2013).

Cacabelos, R., Cacabelos, P., Torrellas, C., Carrera, I. Inmunoterapia en la enfermedad de Alzheimer: Vacunas y Farmacogenómica. Cuadernos de Autoinmunidad, 7: 42-54 (2014).
Cacabelos, R., López-Muñoz, F. The ABCB1 transporter in Alzheimer’s disease. Clin Exp. Pharmacol., 4: e128 (2014).

Cacabelos, R., Torrellas, C., López-Muñoz, F. Epigenomics of Alzheimer’s Disease. J Exp. Clin. Med., 6:75e82 (2014).
Torrellas, C., Carril, J.C., Cacabelos, R. Benefits of Pharmacogenetics in the Management of Hipertensión. J. Pharmacogenomics Pharmacoproteomics, 5:126 (2014).
Aliev, G., Priyadarshini, M., Reddy, V.P., Grieg, N.H., Kaminsky, Y., Cacabelos, R., Ashraf, G.M., Jabir, N.R., Kamal, M.A., Nikolenko, V.N., Zamyatnin, A.A., Benberin, V.V., Bachurin, S.O. Oxidative Stress Mediated Mitochondrial and Vascular Lesions as Markers in the Pathogenesis of Alzheimer Disease. Curr. Med. Chem., 21:2208-2217 (2014).
Cacabelos R. Metabolomics of Epigenetic Drugs: Precautionary Measures, Metabolomics, 4:e126 (2014).

Cacabelos R, Torrellas C. Epigenetic drug discovery for Alzheimers disease. Expert Opin. Drug Discov., 3:1-28 (2014).
Cacabelos, R., Goldgaber, D., Vostrov, A., Matsuki, H., Torrellas, C., Corzo, D., Carril, J.C., Roses, A. APOE-TOMM40 in the Pharmacogenomics of Dementia. J. Pharmacogenomics Pharmacoproteomics, 5:135 (2014).
Siest, G., Medeiros, R., Melichar, B., Stathopoulou, M., Van Schaik, R.H., Cacabelos, R., Abt, P.M., Monteiro, C., Gurwitz, D., Queiroz, J., Mota-Filipe, H., Ndiaye, N.C., Visvikis-Siest, S. Pharmacogenomics: from cell to clinic (Part 1). Pharmacogenomics, 15(5):593-599 (2014).
Siest, G., Medeiros, R., Melichar, B., Stathopoulou, M., Van Schaik, R.H., Cacabelos, R., Abt, P.M., Monteiro, C., Gurwitz, D., Queiroz, J., Mota-Filipe, H., Ndiaye, N.C., Visvikis-Siest, S. Conference scene: pharmacogenomics: from cell to clinic (part 2). Pharmacogenomics, 15:739-744 (2014).
Cacabelos, R. Epigenomic Networking in Drug Development: From Pathogenic Mechanisms to Pharmacogenomics. Drug Dev. Res., 75: 348–365 (2014).

Cacabelos R, Torrellas C, Carrera I, et al. Novel Therapeutic Strategies for Dementia. CNS & neurological disorders drug targets. 2015.
Cacabelos R, Torrellas C, Carrera I. Opportunities in pharmacogenomics for the treatment of Alzheimer’s disease. Future Neurology 05/2015; 10(3):229-252.
Carrera I, Etcheverría I, Fernández-Novoa L, et al. A comparative evaluation of a novel vaccine in APP/PS1 mouse models of Alzheimer’s disease. Biomed Res Int. 2015;2015:807146.
Wang R, Wang H, Carrera I, et al. COPS5 protein overexpression increases amyloid plaque burden, decreases spinophilin-immunoreactive puncta, and exacerbates learning and memory deficits in the mouse brain. J Biol Chem. 2015, 290:9299-309.
Chioua M, Pérez M, Bautista-Aguilera OM, et al. Development of HuperTacrines as non-toxic, cholinesterase inhibitors for the potential treatment of Alzheimer’s disease. Mini Rev Med Chem. 2015;15(8):648-58.
Del Coso J, Lara B, Salinero JJ, et al. CFTR genotype-related body water and electrolyte balance during a marathon. Scand J Med Sci Sports. 2015 Aug 17. doi: 0.1111/sms.12542.
Perianes-Cachero A, Canelles S, Aguado-Llera D, et al. (2015) Reduction in Aβ-induced cell death in the hippocampus of 17β-estradiol-treated female rats is associated with an increase in IGF-I signaling and somatostatinergic tone. J Neurochem. doi: 10.1111/jnc.13381.
Carrera I, Fernandez-Novoa L, Aliev G, et al. (2015) Validating Immunotherapy in Alzheimer’s Disease: The EB101 Vaccine. Current Pharmaceutical Design 10/2015.

Books

Cano Gutiérrez, C.A., Cacabelos, R., Gómez Restrepo, C., Jacquier, M., Lopera, F., Manssur Calderón, R.A., Mantallana Eslava, D.L., Montañés Ríos, P., Román, G., Téllez Vargas, J.E. Consenso Colombiano de Enfermedad de Alzheimer. Noosfera Ed., Santa Fe de Bogotá, 2001.
Cacabelos, R. Enfermedad de Alzheimer. Perspectivas de futuro. En: Libro Blanco sobre la Enfermedad de Alzheimer y Trastornos Afines. R. Fernández-Ballesteros, J. Díez Nicolás (Eds.). Obra Social Caja Madrid, Editorial Médica Panamericana, Madrid, pp. 449-522 (2001).

Cacabelos, R. The histamine-citokine network in Alzheimer disease: Etiopathogenic and pharmacogenomic implications. En: Mapping the Progress of Alzheimer’s and Parkinson’s Disease. Mizuno, Y., Fisher, A., Hanin, I. (Eds.). Advances in Behavioral Biology, 51:59-64 (2002).
Cacabelos, R. Prevención de Riesgo Cerebral en Altos Ejecutivos. En: Emprendedores con Valores. El directivo ante el nuevo encuentro Europa-América. Confederación Española de Directivos y Ejecutivos-CEDE (2002).

Hanin, I., Fisher, A., Cacabelos, R. (Eds.). New Trends in Alzheimer- and Parkinson-Related Disorders. Monduzzi Editore, Bologna, 2003.

Cacabelos, R. Farmacogenómica y Nutracéutica. Progreso Científico y Desarrollo Farmacéutico. Fundación Ebiotec, La Coruña (2004).
Takeda, M., Tanaka, T., Cacabelos, R. (Eds.). Molecular Neurobiology of Alzheimer’s Disease. Karger, Basel (2004).

Hanin, I., Cacabelos, R., Fisher, A. Recent Progress in Alzheimer’s and Parkinson’s Diseases. Taylor & Francis, London (2005).
Cacabelos, R. (Ed.). Molecular Genetics of Alzheimer’s Disease and Aging. Genomic Medicine Series. Methods and Findings in Experimental and Clinical Pharmacology, Prous Science, Barcelona (2005).

Cacabelos R, Carrera I, Bello A, Carril J, Corzo L, Fernández-Novoa L, Fraile C, Lombardi V, Martinez R, Tellado I, Takeda M. (2012) World Guide for Drug Use and Pharmacogenomics. Eds. EuroEspes Publishing Co.; www.pharmacogenomicsguide.com