SLIDE 1
Chronic respiratory disease: towards better treatments
Alaina J. Ammit PhD Alaina.Ammit@uts.edu.au Professor of Respiratory Pharmacology, UTS Director, Woolcock Emphysema Centre, Woolcock Institute of Medical Research
SLIDE 2 Chronic respiratory disease
– 1 in 10 Australians have asthma – More common in males aged 0–14, but among those aged 15 and over, asthma is more common in females
- Chronic Obstructive Pulmonary Disease (COPD)
– In Australia, COPD ranks third behind ischaemic heart disease and stroke as a major cause of disability and early death – 1 in 7 Australians over the age of 40 are affected by COPD – By 2020, COPD is projected to become the third most important chronic illness in the world
Asthma Australia; Australian Institute of Health and Welfare
SLIDE 3 Asthma and airway remodelling
- Acute asthma – bronchoconstriction and difficulty
breathing
- Asthma is a chronic inflammatory condition of the lung
associated with structural remodelling, or thickening, of the airway wall
– Mucus hypersecretion – Neovascularization – Airway fibrosis – Increased airway smooth muscle mass
SLIDE 4
Asthmatic airway Non-asthmatic airway
SLIDE 5 COPD
- Chronic inflammatory disease characterised by progressive lung
function decline
- Main symptoms are breathlessness, cough and sputum production
- Major public health problem worldwide
- Globally, the burden of COPD is projected to increase due to
continued exposure to COPD risk factors:
– tobacco smoke, outdoor air pollution and indoor noxious particles and gases from cooking and heating fires
- Prevalence, morbidity and mortality of COPD are increasing in many
westernised countries and cigarette smoking is the main cause
SLIDE 6
Chronic inflammation in the lungs of people with COPD drives damage and long-term decline in lung function (breathlessness). Current COPD medications don’t slow the accelerated rate of decline
COPD: lung function decline
SLIDE 7
But wait… don’t we have drugs for that already? Target molecular mechanisms to treat chronic respiratory diseases
YES
GOAL
SLIDE 8
SLIDE 9 BUT… they are not always effective…
- Anti-inflammatory corticosteroids and bronchodilatory β2-agonists
are first line therapy
- Although these medicines have proven clinical efficacy, many
respiratory conditions are not responsive:
– severe asthma, COPD, infectious exacerbation
- We urgently require improved and novel ways to treat chronic
respiratory disease when current medicines are ineffective
- Need greater understanding of molecular mechanisms
- This is what my research team does...
SLIDE 10 What are the current issues limiting treatment today? β2-adrenergic receptor desensitization
>5 recent publications in the top respiratory journals (in collaboration with Brian Oliver)
SLIDE 11 What are the current issues limiting treatment today? Cannot repress inflammation in severe asthma and COPD
Current project as an example of our capabilities for potential funding and collaboration with industry partners
SLIDE 12
Harness the power of endogenous anti- inflammatory proteins in COPD
TTP (tristetraprolin) A molecular switch
SLIDE 13
IL-6, IL-8, IL-2, GM- CSF, GRO-α, TNFα
TTP
Tristetraprolin (TTP), a destabilising RNA binding protein, is a critical anti-inflammatory protein that induces the decay of mRNAs encoding several cytokines, including those that drive COPD pathogenesis
Inflammation in COPD
TTP is a molecular switch and is likely turned off under respiratory disease conditions
TTP
SLIDE 14
GOAL
Switch TTP on to turn off inflammatory in COPD
HOW?
SLIDE 15
We can switch TTP on by activating PP2A We can repress inflammation when current medicines (corticosteroids) cannot
SLIDE 16
Target inflammatory mechanisms to treat inflammation and reduce lung function decline in COPD GOAL
The development of novel pharmacotherapeutic anti-inflammatory strategies more effectively
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PP2A activators
