Licastro and Caruso Immunity & Ageing 2010, 7(Suppl 1):S1 http://www.immunityageing.com/content/7/S1/S1 IMMUNITY & AGEING PROCEEDINGS Open Access Predictive diagnostics and personalized medicine for the prevention of chronic degenerative diseases Federico Licastro1*, Calogero Caruso2 From Predictive diagnostics and prevention of chronic degenerative disease Bologna, Italy. 4 December 2009 Abstract Progressive increase of mean age and life expectancy in both industrialized and emerging societies parallels an increment of chronic degenerative diseases (CDD) such as cancer, cardiovascular, autoimmune or neurodegenera- tive diseases among the elderly. CDD are of complex diagnosis, difficult to treat and absorbing an increasing pro- portion in the health care budgets worldwide. However, recent development in modern medicine especially in genetics, proteomics, and informatics is leading to the discovery of biomarkers associated with different CDD that can be used as indicator of disease’s risk in healthy subjects. Therefore, predictive medicine is merging and medical doctors may for the first time anticipate the deleterious effect of CDD and use markers to identify persons with high risk of developing a given CDD before the clinical manifestation of the diseases. This innovative approach may offer substantial advantages, since the promise of personalized medicine is to preserve individual health in people with high risk by starting early treatment or prevention protocols. The pathway is now open, however the road to an effective personalized medicine is still long, several (diagnostic) predictive instruments for different CDD are under development, some ethical issues have to be solved. Operative proposals for the heath care systems are now needed to verify potential benefits of predictive medicine in the clinical practice. In fact, predictive diagnos- tics, personalized medicine and personalized therapy have the potential of changing classical approaches of modern medicine to CDD. Introduction factors. Moreover current therapies are administered A dramatic increase in mean life span and life expec- uniformly across a heterogeneous spectrum of disease tancy, coupled with a significant reduction in early mor- aetiology, severity and genetic background. However, as tality, has lead to a substantial increment in the number large scale investigation platform become a mainstream, of the elderly population in contemporary societies. This modern medicine has the opportunity to expand its demographic picture parallels the merging of a new epi- medical instrumentation to include molecular pheno- demic characterized by chronic age related or degenera- types, genetic background and biomarkers to distinguish tive diseases (CDD). Clinical diagnosis and therapy of clinical subtypes of a single disease to better tailor both these diseases imply multidisciplinary medical potential prevention strategies and/or early intervention approaches and their cost is progressively increasing. protocols for CDD. Most CDD have complex aetiology and pathogenesis. In Therefore, the future treatment of CDD may contem- fact, human CDD are often the consequence of a com- plate primary, secondary or tertiary prevention. Primary plex interplay of genetic, epigenetic and environmental prevention reduces diseases in a population by lowering exposure to casual agents or promoting host resistance * Correspondence: [email protected] and may lead to a decrease in age specific incidence rate 1Department of Experimental Pathology, University of Bologna, Via San orinariseinthemeanageatonsetofagivenCDD. Giacomo 14, 40126, Bologna, Italy Full list of author information is available at the end of the article Secondary prevention limits progression and recurrence © 2010 Licastro and Caruso; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Licastro and Caruso Immunity & Ageing 2010, 7(Suppl 1):S1 Page 2 of 3 http://www.immunityageing.com/content/7/S1/S1 of a disease by early case detection, diagnosis and treat- predicts an event or a non-event in 70% of cases. To ment and reduces the disease prevalence. Tertiary pre- reach this goal a strong association between the mar- vention ameliorates the symptoms and tissue damages kerandagivendiseaseisrequiredwithanunadjusted associated to a given CDD by containing individual dis- relative risk or odds ratio = or > 10.0 [8]. A network ability and dependency and maintaining an acceptable of genetic, phenotypic, epidemiological and clinical fac- quality of life. tors may reach or go above that level of association Predictive diagnostics are merging from the acquisi- and be very informative for the evaluation of individual tion of new phenotypic and genetic markers associated risk for a given CDD. with CDD. This markers are generated by a panomic One area of near future clinical application of these approach to biology of diseases such as genome wide innovative methodologies is pharmacotherapy with the association study, transcriptomics, proteomics and meta- goal of optimizing the therapeutic response and minimiz- bolomics. These disciplines attempt to capture the large ing toxicity and undesired effects [9,10]. For instance, output of an organism DNA, RNA, proteins and meta- Transtuzumab, a monoclonal antibody specific for HER2 bolites with the view that the whole is often greater receptor are only effective in women with HER2 positive than the sum of its parts and subtle critical information breast cancer subtype [11]. Pharmacogenomic may also may be obtained by these methodological sophisticated contribute to identify responders to a given drug and approaches [1,2]. Recent advances in computational ana- radically modify traditional pharmaceutical trials and dis- lysis has increased data availability for predictive medi- ease’s treatment. cine of CDD [3]. To discuss these topics a one day international meet- It is known that individuals are distinguished form ing entitled “Predictive diagnostics and prevention of one another by 0.1% difference in the nucleotide chronic degenerative diseases” was organized by sequence of human genome. These difference are often Dr. Licastro at the Academy of Science of the Bologna in the form of a single base pair or single nucleotide University on December 4th 2009, some of the contri- polymorphism (SNP). Individual SNP usually causes butes to the congress have been collected as full papers only a modest change in the cognate protein concentra- and presented in this special issue of Immunity and tion or function and is of limited information for dis- Aging. ease’s risk evaluation. Therefore, the concomitant The paper presented by Dr. Ravaglia and co-worker presence of several SNPs is more informative to deter- illustrate the relevance of longitudinal population study mine susceptibility to disease development in polygenic such as “the Conselice Study on Brain aging” to gather human condition such as CDD. Finally, in complex new markers linked to the risk of cognitive decline and genetic diseases the genotype confer susceptibility, but dementia in old age and validate risk factors described the clinical presentation of the disease depends upon in other epidemiological investigations. interactions of several different genes with environmen- Dr. Grossi presented a contribution illustrating a new tal factors. statistical algorithm derived from artificial adaptive Proteomic studies may then confirming and extending neural network systems for mining variables from bio- the findings of functional genomic investigations and medical database. This new statistical tool is able to provide novel markers for CDD. describe a connectivity map of factors associated with a Complementary to this global, non-hypothesis-driven disease, the interactions among variables and their rele- methodologies, the candidate gene or marker approach vance with a given disease. evaluates individual marker in association with CDD The article from Dr. Licastro and co-workers pre- based on a prior understanding of its role in the disease. sented an application of the artificial adaptive system on Genetic investigations on CDD are collecting useful a large number of variables collected from “the Conse- information regarding genes associated with the dis- lice Study on Brain aging” longitudinal population inves- ease risk. The goal will be to identify non symptomatic tigation and showed a connectivity map of variables individual with high susceptibility for the disease who associated with the age associated cognitive decline and may benefit from prevention or early intervention pro- dementia. tocols [4,5]. Dr. Tomasi discussed the role of prion proteins on Current risk evaluation is derived from epidemiology cellular kinases and their effects in signal transduction investigation upon large populations and assesses the pathways of neurons in both physiological conditions association of a trait or factor with the clinical out- and human neurodegneration. come (disease manifestation, progression,etc.).Predic- Dr. Ianni and co-workers presented data regarding gly- tive medicine will modify this approach by introducing cosilation profile of plasma purified alpha-1-antichymo- genomic and proteomic profile upon epidemiological trispin (ACT) in patients with Alzheimer’s diseases (AD) investigation