The Duchenne Research Breakthrough Fund was launched eighteen months ago by the Muscular Dystrophy Campaign with the aim to raise funds to accelerate the pace in development of effective treatments for Duchenne muscular dystrophy.
Since launch over £1million has been raised and spent by the Fund thanks to the committed support to families across the UK who have undertaken a range of fundraising activities.
This presentation provides a full update of the Fund, which was presented at a recent review meeting.
5. Paving the road to treatments
Dr Neil Bennett
Research Communications Officer
Dr Alison Stevenson
Senior Grants Manager
Email: n.bennett@muscular-dystrophy.org
Website: www.muscular-dystrophy.org
6. Overview
• The research department
• Clinical trial update
• Why and how we fund research
• Update on Duchenne research projects
• The future
7. Our Activities
• Research grant program
• Applications undergo a rigorous peer-review process
• Only the best science is funded
• Facilitate collaboration/communication between scientists
• Organising conferences and workshops
• Funding support for the European Neuromuscular Centre
• Research Communications Service
• Target Research
• Weekly web-based news service
• Information on clinical trials
8. Exon-skipping clinical trials
• Two initiatives currently trialling exon-skipping technology
• Prosensa/GSK and Sarepta Therapeutics targeting exon 51
• Eteplirsen trial - slower decline in walking ability
• The distance boys can walk is stable after 120 weeks
• Very small phase 2b study - further trials required
• Drisapersen phase 3 trial failed to show effectiveness
• Large phase 3 trial of 180 boys
• Companies now analysing the data in more detail
• Prosensa testing molecular patches to exons 44, 45, 53
9. Other clinical trials
• Ataluren for Duchenne muscular dystrophy
• Phase 3 trial under way
• Could help cells overcome nonsense mutations
• SMT-C1100
• Phase 1b trial started
• Has the potential to increase production of utrophin
• Other trials include
• HT-100
• Stem cells
10. Why fund research?
• Not all potential treatments in clinical trials will work
• We don’t know which therapeutic approach will work best
• Initial treatments may need to be improved
• Different approaches may be needed in different boys
• Exploring a broad range of therapeutic approaches will
maximise the chance of finding an effective treatment
11. Duchenne Research:
a focus within the charity
• The charity was founded in 1959 by a clinician, a scientist,
and the parent of a boy with Duchenne
• A strong focus on funding research to find treatments and
eventually cures
• In the last 10 years the charity has invested:
• £4.3M into Duchenne research
• £2.7M into UK muscle centres
• £0.5M into databases
• Spearheaded a number of promising, potential treatments
12. How do we choose research projects
Research Grant Application
Lay Application
Lay Research Panel
Scientific Application
International Peer Review
Medical Research Committee
Board of Trustees Meeting
13. Peer Review
• What is it Peer Review?
• It is used to assess the quality of scientific ideas
• Independent scrutiny by qualified experts (peers)
• What does it tell you?
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Scientifically valid, significant and original
Timely and achievable
Not unnecessarily duplicating other work
Using appropriate methodologies
Carried out by researchers with the right skills and facilities
Value for money
Fits with our research strategy
Quality control for science
14. Strategic topics
1. Developing potential therapeutic approaches
2. Promoting clinical trial readiness
3. Clinical trials and pilot studies
4. Understanding the cause of neuromuscular diseases
5. Building clinical and scientific capacity
6. Improving quality of life
7. Foster sharing of knowledge and networking within the
scientific community in the UK and internationally
8. Building partnerships
15. The research we fund
Clinical trials
infrastructure
Improved diagnostics
Better disease characterisation
Therapy
delivery
Gene identification
Understanding
muscle function
Understanding
what goes wrong
Well characterised
animal models
Basic Science
Therapeutic
concepts
Testing drugs in
animal models
Preclinical
Studies
Regulatory
affairs
16. The research we fund
Clinical trials
infrastructure
Improved diagnostics
Better disease characterisation
Therapy
delivery
Gene identification
Understanding
muscle function
Understanding
what goes wrong
Well characterised
animal models
Basic Science
Therapeutic
concepts
Testing drugs in
animal models
Preclinical
Studies
Regulatory
affairs
17. Ongoing Duchenne research projects
Professor George Dickson is using exon
skipping to boost muscle growth by blocking
the activity of a protein called myostatin.
Professor Nic Wells at the Royal Veterinary
College is investigating ways to make blood
vessels more leaky to improve the delivery of
molecular patches to the muscles
Professor Matthew Wood at the
University of Oxford is looking at using
short protein fragments, called
peptides, to improve the delivery of
the molecular patches to the heart
18. New research projects
• The 2013 grant round focused on research for Duchenne
muscular dystrophy
• Seven projects were awarded; developing various potential
therapeutic approaches
• With the contribution of other Duchenne charities through
the Duchenne Forum our commitment for the next 4 years
will be £850,000
19. New research projects
Dr Jennifer Pell (University of Cambridge)
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£121,000 for 2 years
Investigating inflammation in Duchenne
muscular dystrophy
Prof Kay Davies (Oxford University)
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£128,000 for 2 years
Developing small molecules to target
Duchenne muscular dystrophy
•Dr Angela Russell (Oxford University)
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£110,000 for 4 year PhD studentship
Understanding how small molecules can
increase levels of utrophin
20. New research projects
Prof George Dickson (RHUL)
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£80,000 for 3 year PhD studentship
Genome surgery for Duchenne muscular dystrophy
•Prof George Dickson (RHUL)
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£180,000 for 3 years
Development of a triple-transplicing system
for Duchenne muscular dystrophy
Prof Jenny Morgan (UCL)
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£111,000 for 4 year PhD studentship
Altering the muscle environment to
influence stem cell behaviour
21. New research projects
Prof Matthew Wood (Oxford University)
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£110,000 for 4 year PhD studentship
Searching for biomarkers of Duchenne
muscular dystrophy
22. Translational research
• The transfer of scientific discoveries into clinical applications
Bench – to – Bedside
• Several challenges due to the rarity of the conditions
• How to find the patients
• Assessing the benefit of a potential treatment
• The promotion of public-private partnership is important
particularly with regards to the cost
24. Supporting clinical (trial) infrastructure
• Clinical Training and Research Fellowships
• Clinicians who undertake a research project
• Current call for applications for a Fellow who will
focus on Duchenne muscular dystrophy
• Clinical Trial Co-ordinators
• Based at the muscle centres in London and Newcastle
• Help the centres with the administrative burden of
organising clinical trials
• Neuromuscular database (Northstar)
• Collects natural history data from boys with Duchenne
• Currently being expanded to collect data from boys no
longer able to walk
25. Into the future…
• More and more clinical trials starting to take place
BUT…
• Clinical trials are expensive and don’t always work
HOWEVER…
• There is a growing confidence in the scientific community
that therapies will start to appear on the market in the next
few years
27. Speeding up access to drugs for
rare diseases
Nic Bungay
Director of Care, Campaigns & Information
Rebecca Johnston
Neuromuscular Outreach Officer
28. Introduction and Context
• Potential
treatments on the horizon
• Regulatory hurdles
• Approval process
• Funding arrangements
• Parliamentary activity
29. Who do we need to influence?
• European Medicines Agency and relevant
Committees
• Medicines and Healthcare products
Regulatory Agency (MHRA)
• National Institute for Health and Clinical
Excellence (NICE)
• NHS England
• Health Ministers
30. Parliamentary Inquiry – background
All Party Parliamentary Group for Muscular
Dystrophy inquiry in 2013:
“To determine the future of access to high
cost drugs for orphan diseases in the NHS;
the regulatory and reimbursement
environment for orphan drugs; and the future
of funding arrangements for research into
treatments for children and adults
with rare diseases”
31. Parliamentary Inquiry – evidence
• Researchers and pharmaceutical
companies
• Patient and family views
• Regulatory, approval and funding
perspective
• Department of Health
• Charitable organisations
32. Parliamentary Inquiry – recommendations
• Government should establish a ring-fenced fund
for rare disease drugs
• NICE should assess treatments for rare conditions
differently from less rare conditions
• the Medicines and Healthcare Products Regulatory
Agency (MHRA), NICE and NHS England should
speed up access to life-changing drugs after the
final stages of clinical trials
• NHS England should ensure specialist centres are
equipped with an appropriate range of health
professionals to deliver treatments
33. Parliamentary Inquiry – report and follow-up
•Report presented to Health Minister Norman Lamb
in September 2013 at MDC parliamentary reception
• Subsequent roundtable and one-to-one meetings
with MPs and Peers, MHRA, NICE and NHS England
• Parliamentary pressure – debates and questions in
the House of Commons and House of Lords
34. Thank you for your support
Rebecca Johnson
020 7803 2865
r.johnson@muscular-dystrophy.org
37. What can I do?
• Place collection tins in your local area
• Make a regular donation by Direct Debit
• Take part in our events programme
• Help out at an organised collection
• Organise your own fundraising event
• Set up a Family Fund
Developing potential therapeutic approachesGreat advances made in therapeutic approaches but still a number of conditions where underlying biological process is well studied but no effective treatment available.Promoting clinical trial readinessClinical trials and pilot studiesUnderstanding the cause of neuromuscular diseases