Some of the latest progress for the prevention, diagnosis and treatment of aspergillosis
Support Meeting for Aspergillosis Patients LED BY GRAHAM ATHERTON SUPPORTED BY MARIE KIRWAN, GEORGINA POWELL & DEBBIE KENNEDY NAC CENTRE MANAGER CHRIS HARRIS ADVANCES FOR THE PREVENTION, DETECTION & TREATMENT OF ASPERGILLOSIS: GRAHAM ATHERTON NATIONAL ASPERGILLOSIS CENTRE UHSM MANCHESTERFungal Research Trust
Programme 1pm Introduction 1:05 Graham Atherton 2:00 Tea & Coffee 2.10 FRT becomes FIT 2.30 New meeting location & format 3:00 Close
Latest Advances- Aspergillosis By Graham Atherton
PreventionIdentifying vulnerable people (Paul Bowyers Work)Cleaning damp homesPreventing contact with strain of aspergillus that are already resistant to azole antifungals (multidisciplinary) due to agricultural use.
Identifying the vulnerable20 years ago researcher worked on one or two genes at a time
Time1-2 genes – 3 years!!SlowFew genes testedResults are isolated – we can’t see how other genes are acting
Gene interaction - complexity One pathway 8 Genes (proteins) Change in one gene affects all others
How do we look at WHOLE picture?Microchip arrays4000 genes tested (10 000 in human genome)
New technology Thousands of genes tested• Microchip arrays• Genome sequencing – now very cheap and within a short time will be available to everyone (Host sequence)• Has already been carried out on many Aspergillus strains from clinic LOTS OF INFORMATION!
Our Research (Paul Bowyer) Carried out with your help!Identifying•How fungus fights antifungal drugs (so we can beat it)•What makes people vulnerable to infection & allergyWe have detected several (>20-30?)genes that may beimportant in all of these processes. Will now look athow these change in vulnerable people.Time needed to do all of this? – 12 months
Cleaning up damp homesDamp homes are clearly bad for health – for our patients even more so‘Green’ groups push for houses that are sealed and allow no fresh air in = dampJust launched a big push to redress the balance with a construction industry education program run by ISSE (www.isse.org.uk)
Damp homesWorking on help & advice for homeowners/landlords Reliable signs of the presence of mould & damp that indicate problems for homeowner Work to establish guidelines for GP to recognise health problems caused by damp homes
Resistant Aspergillus in the EnvironmentIt has been discovered that there are many strains of Aspergillus (including fumigatus) that are already resistant to some antifungal drugs.There are versions of azole antifungals used as pesticides – work is underway internationally to limit their use
DiagnosisExisting techniques tend to be slow, both at identifyingspecies and testing it for resistance to antifungal drugs•Genomics – Paul Bowyer’s work on discovering whatgenes are important for resistance/infection/allergy•Personalised medicine•Computer programs (algorithms) to distinguishinvasive from colonised
Treatment• New drugs• Better use if drugs – personalising medicine• Genotyping – cheap & available• New types of delivery – Nanotechnology• Vaccines• New lungs?? – Advances in transplant – Growing new lungs!!
New drugs• Antifungals – – micafungin (echinocandin IV – isolated from another fungus (Coleophorma)) – Anidulafungin (echinocandin) Both useful additions as they work differently to azoles. But what else??
Future drugsF2G (Manchester) have just received $30 millionfunding for their new drug targets – several newpossible drugs, new targets, new mechanisms.10 – 15 years away.
Future antifungal therapiesVaccines. Recent papers have been published (by our close colleagues in California - David Stevens) showing that vaccines made from yeast work very well to prevent Aspergillus infection in mice.Immunity boosting. Antibody therapy for those unable to produce their ownNanotechnology
Nanotechnology• A completely new way to get drugs into human tissue via penetrating skin. Up until now we have had to use solvents – these tend to be toxic, limiting use.• We can now enclose drugs in extremely small nanoparticles which can pass through cells & skin (and importantly mucus) with no further help – already being done for amphotericin B, silver & others (new lease of life for older more toxic antifungals)• Already used as a cream for nail infection but being tested on CF patients to eradicate bacterial and fungal lung colonisation with some success – improves antifungal activity.• Possible to target specific organs!
NanoparticlesThese are up to 250 times smaller than width of human hair
NanoparticlesNext step could be to try similar on deeper infections: ABPA, SAFS, CPA and so on
Lung – highly complexBlood vesselsAirwaysDozens of different cell typesHighly organised – absolutely no good if we get it slightly wrongHow can we possibly replicate that structure
Stem cellsWe are made up of billions of individual cells but we all started off as a single cell – the fertilised egg.We now know that a small number of highly specialised cells are the seeds for entire organs once developmental growth has completed in the womb – these are referred to as stem cells
Current ResearchStem cells are extremely hard to find and very rare – only recently has this been possible (2011)Lung cell research – Boston University Center for Regenerative MedicineJune 2012 reporthttp://www.bu.edu/today/2012/from-stem-cells-to- lung-cells/
From stem cells to lung cells - 1Stem cell will grow and divide to reproduce itself just as any other cell will – until it is given the signal to start producing lung tissueBoston Team created a stem cell that glowed green once it has been activated to produce lung tissue
From stem cells to lung cells - 2Take mouse lungs and remove all cells to leave a bare ‘scaffold’Add lung stem cells, activate and grow
From stem cells to lung cells – 3 Does it function as a lung?Rat lung grown for 1 weekTransplanted into a rat where it worked for 2 hours! Structurally these are real, working lungs
Repairing lung – reconditioning4 out of 5 lungs received for transplant are of insufficient condition to use as much damage is often done prior to removalNewcastle University Hospital (2012) are developing a way to ‘recondition’ unsuitable lungs by keeping them functioning ‘ex vivo’ for several days after donation, treating them with antibiotics (antifungals?)Lungs become usable!!
The future for stem cellsHuman research?Intriguingly research shows stem cells repairing lungs as a completely natural process after damage (small structures) – perhaps we can harness this? Boost it by adding new stem cells or stimulating those already there?Host of possibilities!
Summing upModern genetic research progresses much faster than 20 years agoTools are now much more powerfulStem cell & genomics research is in its infancy – imagine where we will be in 10 - 20 years time??Rate limiting factor – availability of patient data & individuals prepared to help e.g. before the NAC it would have been very difficult to collect data on as many CPA patients as we can now.
Patient Information – future improvementsNHS IT records database – should include every record of every patient & will allow researchers to browse cases & collect research information very efficiently – to come in 2015Cost, privacy worries & politics may prevent this happening or reduce its impact – another moral dilemma.
Changes at FRTFungal Research Trust = Fungal Infection Trust
FRT is changing its name to FITWhy?•FIT will continue to fund research exactly as FRT wasalways very successful at doing•FIT will also carry out a number of projects abroad toattempt to reach the many millions of infected peoplein countries like Africa & India via their governments.This is subject to quite separate funding fromdifferent sources.•Every £ raised for research in the UK for FIT will stillgo towards the same research funded by FRT.
When will FIT start?Within weeks FIT will become active and NEW initiatives will be carried out under that new nameFrom January 2013 FRT will have effectively transferred completely to FIT
Student competitionsAim: Building awareness amongst younger people & parents UPDATE: 3-400 entries – Has now been judged and winners chosen Winners will be announced at the Manchester Science Festival, where we will also hold a 4 day education and awareness exhibition using the winning images to help illustrate various types of fungal infection www.manchestersciencefestival.com/
Annual Survey of Patients105 patients asked10% had been to a Support Meeting9% viewed online26% viewed recordings47% do not use Aspergillus WebsiteApproximately 50% do not use the internetWE NEED TO SUPPORT THOSE PEOPLE NOT USING INTERNET BETTER
Annual Survey of PatientsWhy don’t you attend the Aspergillosis Support Meeting?
Time and PlaceMost attend clinic on FridayCloser to Clinic the betterMeeting now to be held in Friday afternoons at 1.30pm Hope to move the meeting to a room in the North West Lung CentreProvide tea & coffee (possibly even sandwiches) from 1pm – there is a small socialising area
Format & contentNumbers attending smallerSome comments that content is less relevant to all and a return to talks on aspergillosis would be welcomeSuggestions:More involvement from centre staffMore, shorter sessions in specific areas every month
Other suggestionsDoctor present for 20 min at every meetingWe have a session held by a patient – once per month (volunteers?)Your choice of subjectPatient leader(s)Comment sheet to be available at each meeting for anonymous constructive criticism
New Patient MeetingFirst new meeting is on the third Friday of October – the 19thIt will take place in the Altounyan Suite, a short walk from the Chest clinic
Altounyan SuiteNO access from outside ONLY via Chest Clinic
Directions to Altounyan• From main entrance: follow hospital corridor and turn into Chest Clinic corridor. Through double doors and reception is in front of you. *Altounyan Suite is signposted from here.• Pass reception on the right and continue down corridor passing Lung Function room on the left and go through double doors at the end.• There is another set of double doors in front of you which is locked. Push intercom button and ask for access.• Carry straight on following signs, though the door in front of you passing the stairwell on your right. Go through final single door and enter the small atrium.• The Altounyan suite is the room on your right.
Thank You“The best chance we have of beating this illness is to work together” Living with it, Working with it, Treating it Fungal Research Trust