Human longevity: latest insights. Dr Christoph Nabholz, Head R&D Life & Health, NGIC June 2017

Transcription

1 Human longevity: latest insights Dr Christoph Nabholz, Head R&D Life & Health, NGIC June 2017

2 Age adjusted deaths rates and life expectancy developments in the US Source: 2

3 To further improve life expectancy mortality, improvements have to come from age associated chronic diseases Hygiene Food 100 Antibiotics Sanitation Statins Smoker campaigns Delay of old age mortality over 80 years years years years 0-14 years Infant mortality reduction Source: Christensen et al.; Lancet 2009; 374: Age-specific contributions to life expectancy in women from 1850 to

4 Life expectancy rates are a result of dynamic changes in disease management Source: 4

5 Mortality rates per 100,000 (age adjusted) In the US, CVD and cancer mortality have improved, while diabetes and COPD have increased over the last decades General population statistics Source: Global Burden of Disease % change Heart diseases Cancer Stroke COPD Transport injuries Diabetes COPD Chronic Obstructive Pulmonary Disease

6 For the first time in more than two decades, life expectancy in the US declined Life expectancy fell by 0.1 year in 2015 The overall death rate rose 1.2% in 2015, its first uptick since 1999 Life expectancy last fell during the peak of the HIV/Aids crisis in 1993 Possible drivers: obesity levels, ageing population, economic struggles and drug misuse Mortality rates for people in their 30s, 40s and 50s, are flat or increasing Source: NCHS Data Brief No. 267, Dec

7 US death rates rose for eight of the top 10 leading causes of death in 2015 Heart disease increased (+0.9%) Ramifications of obesity? Death rate from cancer declined (-1.7%) fewer people are smoking, early detection, new treatments Largest rate jump - Alzheimer s (+15.7%) Unintentional injuries (+6.7%) Overdoses from drugs, alcohol and other chemicals Motor vehicle crashes and other accidents Stroke (+3%), Diabetes (+1.9%), Kidney disease (+1.5%), Suicide (+2.3%) Source: NCHS Data Brief No. 267, Dec

8 Mortality in England and Wales was reversed in 2011 with 2015 being one of the largest increases in deaths in the post-war period Age-standardised death rate per 100,000 England and Wales, Percentage increase in death rates at individual years; 2014 to 2015 in England and Wales Dementia was the major contributor, based on reported causes of death Excess deaths are in the older population, who are most dependent on health and social care Source: Hiam et al

9 % total death High-Income Countries, Global mortality projection 2030 shows differential outcomes by disease Rank Cause Ischaemic heart disease Stroke Alzheimer's disease and other dementias Trachea, bronchus, lung cancers Lower respiratory infections Chronic obstructive pulmonary disease Colon and rectum cancers Diabetes mellitus Hypertensive heart disease Kidney diseases Pancreas cancer Breast cancer Prostate cancer Stomach cancer Lymphomas, multiple myeloma Self-harm Liver cancer Cirrhosis of the liver Falls Endocrine, blood, immune disorders % deaths Deaths per 100, % deaths Deaths per 100, Source: WHO Global Health Estimates 9

10 International life expectancy projected for males at age Source: Canada Pension Plan Projection; Ménard,

11 Where will future improvements come from? 11

12 Bio-medical technology and behavioural change are believed to be the major forces shaping future mortality 8% Bio-medical technology 9% 29% Behavioral changes Health care systems 9% New/resurgent diseases Population composition Environmental changes 17% 28% Source: National Population Projections Expert Advisory Group

13 Top 10 risk factors that account for mortality in the USA in 2015 Diabetes CVD Cancer Source: Institute for Health Metrics and Evaluation (IHME). GBD Compare. Seattle, WA: IHME, University of Washington, Available from Accessed 22 March

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15 Interventions that slow ageing will have a greater effect on quality of life compared to disease specific approaches Disease specific approach allows to live longer but suffering from multiple diseases or disabilities This increases the need for care of elderly patients living in reduced quality of life Biology of ageing aims at enhancing healthy longevity; addresses the longevity dividend Ageing diseases: Heart disease, diabetes, cancer, dementia Key criteria: Ease of implementation What is missing? Lack of biomarkers: required true ageing biomarkers (epigenetic, metabolomic etc) Missing FDA approval: may yet not be possible to receive approval for ageing intervention TAME trials: Targeting Ageing with Metformin; expected delay in order of 15-30%; first possible case for FDA approval Open question: will future centenarians have fulfilling lives with sudden collapse or suffer from multiple chronic diseases Effective when started in mid-life Benefits outweigh the risk 15

16 Ageing interventions aim at enhancing healthy longevity Promising ageing interventions: Dietary restriction: while not universally applicable to lab models, it shows significant increases in life span Exercise: proven enhanced health span but poor compliance in elderly patients mtor inhibitors: rapamycin expands life span in mice; reverses cardiac decline and improves immune function (rejuvenate immune stem cells) Metformin and acarbose: antidiabetic drugs that expand life span Insulin response; Diabetes; Cardiac health; Immune response Modifiers of senescence: telomere dysfunction leads to senescence Hormonal and circulating factors: sex-steroids, growth hormone, insulin-like growth factor; blood donation from young adults increases life span in mice; Alzheimer tests with plasma ongoing NAD precursors and sirtuin activators: improve health span; muscle ageing and cognitive decline Mitochondria therapeutics: free radical theory; augmented mitochondrial function (energy, biogenesis, antioxidants, NAD precursor) Programmed cell death; Hormone lifecycle; Mitochondrial function; Cognitive health 16

17 Top bio-medical advances that reduce mortality are addressing disease monitoring, diagnostics and medical interventions Therapy Technology innovation Heart disease management improves Minimally invasive and robotic surgery Combination drug therapy extends HIV survival CT, MRI and functional MRI scanning Hepatitis C cure comes to market Targeted cancer immuno therapy matures ehealth and telemedicine Mobile biovital sign monitoring Genetic medicine 17

18 Clinical trial landscape for cancer, CVD and Alzheimer s PHASE PHASE 1 40 PHASE 2 AD Source: CVD 615 PHASE PHASE 4 Cancer 18

19 Disruptive technologies with potential high impact to health outcomes The Internet of Things Next-generation genomics Health and chronic disease monitoring Advanced robotics Robotic surgery and prosthetics Near-autonomous vehicles Reduction in car accidents Source: McKinsey Global Institute 2013 Predictive health analytics 3D printing Organ bioprinting Advanced materials Nanodrugs 19

20 Genetic Medicine Next-generation genomics 20

21 Rapid evolution of genetic testing technologies observed since the human genome sequence in 2003 Whole Exome Sequencing Single Gene Testing Whole Genome Sequencing Gene Panels

22 Full genome sequencing has becomes affordable $100'000'000 Sequencing costs per genome $10'000'000 $1M genome 2008 $1'000'000 $100'000 $10K genome 2011 $10'000 $1'000 $100 genome? $100 Sanger sequencing Source: NIH National Human Genome Research Institute Next generation sequencing Emerging sequencing technologies 22

23 Over the last two decades many cancer genes have been identified with various relative cancer risks in different cancer sites Cancer site Relative Risk 5.0 Family studies Relative Risk 1.5 and >5.0 Resequencing Relative Risk 1.01and >1.5 Genome-wide association studies Lung RB1, TP53 Breast BRCA1, BRCA2, TP53, PTEN, SK11, CDH1 CHEK2, ATM, PALB2, BRIP1 CASP8, FGFR2, MAP3K1, 8q24, 5p, TOX3, 2q, 6q22, LSP1 Colon and rectum APC, MLH1, MSH2, MSH6, PMS2 APC (I1307K), BLM MUTYH, CASP8, 8q24, 8q23 (EIF3H), 10p14, 11q23, CRAC1, SMAD7 Prostate BRCA2 8q24 rs , rs721048, NBS1, EHBP1, TCF2, CTBP2, JAZF1, MSMB, LMTK2, KLK3, SLC22A3 Pancreas BRCA2, CDKN2A, STK11, TP53, PRSS1, SPINK1 BRCA1, MSH2, MLH1 rs , rs (CHRNA3, CHRNB4, CHRNA5) Source: Foulkes W; N Engl J Med; 2008;359:

24 Liquid Biopsy - a new cancer blood test 24

25 How is cancer diagnosed today? Most cancers are detected during Routine screening examination, physical examination or an investigation prompted by symptoms Imaging tests (X-rays, MRI, CT) help determine a cancer's location To confirm the diagnosis of most solid cancers, a biopsy is performed A biopsy is the removal of tissue (needle, endoscope or surgery) from a suspected tumour to study under a microscope to check for cancer cells (histopathology) Results of the histopathology, together with physical examination and imaging tests, form the basis of cancer staging and grading 25

26 Liquid Biopsy a new molecular cancer blood test to screen for acquired mutations in cancer driver genes Liquid biopsy is the term used to describe a molecular test done on a sample of blood (or other bodily fluids such as plasma, cerebrospinal fluid, or urine) to look for tumour material circulating in the blood such as: circulating tumour cells (CTCs) cell free DNA (cfdna) exosomes Source: 26

27 Very low abundance of CTCs and cfdna in blood sample 10 ml Whole Blood 50 billion RBCs 50 million WBCs CTCs tcfdna 0-1 cfdna

28 Note! A positive liquid biopsy test does not confirm the presence of cancer! (nor does a negative liquid biopsy exclude the presence of cancer) 28

29 Conclusion 29

30 Summary Cardiovascular disease, cancer and Alzheimer s disease are the key drivers of mortality Managing health risk factors will be key to extend life expectancy Biomedical technology and behavioural changes are believed to be the major forces shaping future mortality The next generation genomics is a disruptive force to our current health management systems Genetic technology is a key enabler of personalized medicine approaches Liquid biopsy diagnostics is aiding personalized cancer therapy and gives hope to improved cancer survival rates Cancer products need to proactively upgrade their definitions to manage claims exposure due to new diagnostics such as liquid biopsy 30

31 Questions? Dr Christoph Nabholz, Head R&D Life & Health, NGIC June 2017

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