1. The First1000days project Sergio Pecorelli RAMAZZINI Days 2017
Carpi (MO)
October 26th-28th, 2017

2. Aging population and chronic diseases rise worldwide
Number 60+
868m
12%
of total worldwide population
1.3b
16%
2.03b
21%
2014
2030
2050
Deaths in millions
Cancer
Ischaemic heart disease
Cerebrovascular disease
Acute respiratory infections
Perinatal conditions
HIV/AIDS
Road traffic accidents
Tubercolosis
Malaria

3. The world wide demographic transition and socio-cultural globalization are tangibly changing populations’ disease burden and health needs
Population ageing and preventable risk factors are increasing NCDs’ incidence undermining the sustainability of the healthcare systems
Scientific research boosted the development of innovative approaches (educational, empowerment, clinical) targeting the individual BEFORE the disease onset (Precision health)
Precision health applied to network medicine leads to Health & Wealth of population in the environment
Rationale

4. Increased NCD risk The most effective anti-inflammatory medicine
Health stressors
Hormonal factors
Behavioral factors
Chemical stressors
Non-chemical stressors
Modern lifestyle
Diets
Microbial patterns
Physical excercise
Mood, behaviour, development, degeneration
Metabolic responses
Cardiovascular response
Inflammation
and altered immune functions
Stress and HPA responses
Gastrointestinal inflammation
Joints and tissues
Lung development and fuction
Multisystem effect
Tissue damage, oxidative stress and tissue repair
Increased NCD risk

5. The Brescia Industries Association (ABI) and Brescia+ consortium
In 2015 the Brescia Industries Association (AIB) promoted the Brescia+ consortium representing the different stakeholders of the civil society (Comune of Brescia, Universities of Brescia, Industries, Chamber of commerce, Foundations …) with the intent to facilitate the implementation of multidisciplinary projects with social, economic and technological impact in the area of Brescia.

6. The first1000days project: the flagship initiative of Brescia+ consortium
In 2015 Sergio Pecorelli proposed AIB (Brescia Industries Association) to fund a project focused on the real-world implementation of the Developmental Origin of Health and Diseases (DOHaD) concepts within the newly born Brescia+ Consortium.
The AIB accepted the proposal and funded the Start-up phase of the first1000days project.

7. First1000days key concepts
The first1000days project holistically focuses on bio-psycho-socio-economic determinants of NCDs implementing prevention in the earliest phases of life
It aims to build a sustainable and cost-effective preventive process promoting health and wellness of the population through personalized care, impacting at the same time on the welfare
Precision health approaches should be implemented in real world settings to improve health outcomes and quality of life with attentive assessement of their appropriateness and effectiveness
A lean Project governance to facilitate project implementation with third parts
Synergic partnership with global institution to identify/deploy cutting edge solutions to prevent non-communicable diseases

8. Pre-conceptional phase Early stages of pregnancy
Target population
The environment and the characteristics of an individual have a greater impact during early stages of life and will affect health and wellbeing across the lifespan. The first1000days project focuses on the following life stages:
Pre-conceptional phase
Early stages of pregnancy
Late stages of pregnancy
Early childhood
Individuals enrolled in the project should include fathers, mothers and fetus/child

9. 1000 days in a lifetime Risk High risk trajectory low risk trajectory
Affected adult: interventions have limited effect
The first1000days of human development including preconcetpion and pregnancy phases accounts for the 70% of individual future life.
Adult: screening may be too late to reduce risk
Risk
Mother and infant effective point to intervene
Child/adolescent effective point to intervene
High risk trajectory
Future Parents
Prepare
For
Conception
low risk trajectory
Life course
Preconception
Plasticity
Detrimental effects of lifestyle challenges/increasing mismatch

10. Chronic disease prevention: a life course approach
Pre-conception
Preventable risk
Fetal life
Infancy and childhood
Adolescence
Adult life
Older ages
Cumulative incidence
Genetic susceptibility

11. Putative effects of exercise and obesity on the predisposition to metabolic diseases
In response to exercise or diet, the epigenome of gametes (depicted here for spermatozoa) is remodelled. b | After fertilization, these epigenetic changes will affect the developmental programming of the embryo. In utero, the developing embryo is susceptible to other environmental influences from the mother that can potentiate or suppress signals from the gametes. c | Exercise might influence the spermatozoan epigenome and enable transmission of epigenetic information to affect the development of the central nervous system and brain processes such as feeding behaviour. This process could lead to positive metabolic outcomes. Alternatively, according to the thrifty phenotype hypothesis, if exercise triggers an epigenetic response that is similar to caloric restriction of the gamete, the offspring might have a predisposition for metabolic disease when faced with a state of food abundance due to an increased fat storage capacity. Obese fathers could transmit epigenetic markers on genes that regulate brain development and appetite control, thereby predisposing their offspring to obesity. d | Epigenetic inheritance might be propagated to successive generations by so-called transgenerational epigenetic inheritance.

12. Vision: the three pillars
By focusing on the very early stages of development of the individual, this project aims at developing an innovative and personalized care model through the integration of:
Clinical, molecular and exposome evaluation processes
Personalized education and empowerment programs
Use of portable devices for real-time monitoring of clinical/behavioral/environmental/lifestyle information
A quick one-liner summary that combines your vision/product and the mission of your company
Keep it short and memorable
Try: making it relatable… as in “We are X for Y”
(“We are AirBNB for Event Spaces”)
(“We are the Starbucks of Frozen Yogurt”)

13. Objectives
Profile the molecular traits (Genome, Epigenome, Microbiome, Metabolome…) of enrolled individuals to identify critical biomarkers of NCDs’ susceptibility
Assessment of the exposome of the individuals to identify causal relationships between specific exposures and phenotypic expression
Implement validated educational interventions in real world settings individualized according to risk stratification
Use devices/wearable technologies to set up a real-time monitoring of health parameters/lifestyle and bidirectional communication between the individual and the healthcare professional .

14. Wearables/portable devices
For a more sophisticated assessment of the enrolled individuals we think that the use of portable devices could provide critical information to associate with clinical/biological data about the environment and the lifestyle, using minimally invasive approaches.
Those data may include:
Hearth monitoring devices,
Sweat testing
Sleep monitoring
Physical activity monitoring …

15. CSMI - Center for Multi- Sector Services and Technology Transfer
The Headquarter of the First1000Days Project will be located at CSMT (Center for Multi- Sector Services and Technology Transfer), a private/public facility where managing/logistic activities will be carried out:
Lab spaces
Auditorium/Meetings spaces
Ambulatories
Management offices

16. Short term end-points (0-3 years):
Expected project outcomes
The first1000days project aims to identify causal relationships whose effect could manifest across the lifespan of the individual; it is therefore critical to identify short, medium and long term endpoints.
Environment influence
Lifestyle impact
Molecular profile
Short term end-points (0-3 years):
Neurodevelopmental disorders
Medium term end-points (3-6 years):
Behavioral/psicological disorders; overweight/obesity
Long term end-points (more than3 years):
Non-communicable diseases

17. Press room
Compound annual growth rate (CAGR) is a business and investing specific term for the geometric progression ratio that provides a constant rate of return over the time period.[1][2] CAGR is not an accounting term, but it is often used to describe some element of the business, for example revenue, units delivered, registered users, etc. CAGR dampens the effect of volatility of periodic returns that can render arithmetic means irrelevant. It is particularly useful to compare growth rates from different data sets such as revenue growth of companies in the same industry.[3]

18. Development phases Mission/vision/strategy Lean organization Scale up
Organizational flow
Mission/vision/strategy
Lean organization
Scale up 1 2 3 4 5
Ideation
Concepting
Commitment
Implementation
Scaling 6
Establishing
DOHaD concept proposed as flagship initiative
- AIB fundraises the start-up
- Advisory board is gathered
- Concepts are translated into an Action Plan
- Infrastructures are developed (Managing, sample collection, biobank…)
Processes are consolidated and validated
The project is sustainable from both the infrastructure and economic PoV
Seed investment (AIB)
Angel investment
(Local banks, grants)
Series A investment
(Strategic partners, funds…)
Fundraising steps

19. The First1000days project
Sergio Pecorelli
Thank you!