Novel tissue implantable slow release tablet therapy to prevent scarring

Lead Research Organisation: University College London
Department Name: Institute of Ophthalmology

Abstract

There are no licensed treatments to prevent scarring in the human body. Scarring plays a part in most of the major blinding conditions in the world today. It is also important in many lung, heart, kidney, intestinal, brain and skin conditions.

The group of eye diseases called glaucoma are the commonest cause of irreversible blindness worldwide and the commonest reason for an eye outpatient appointment. In glaucoma the nerve carrying vision to the brain gradually collapses. We treat glaucoma by lowering the eye pressure. We can create a new eye drainage channel. Unfortunately this fails due to scarring. In our recent long term surgery study, in patients who had minimal scarring with low pressures not one patient got worse over nearly a decade. In contrast if scarring was bad 24% got worse. The problem is we can only achieve this in 30% of people using an anticancer agent called 5-fluorouracil.

We have discovered that inhibiting enzymes called matrix metalloproteinases dramatically reduces scarring. When we inject this after glaucoma surgery we greatly reduce scarring, more than any anticancer agent we currently use. The problem is we have to inject the eye many times. We have now invented a way to make it into a tiny tablet which is painlessly placed into the operation area. This releases the drug at just the right level. A pilot study has shown this tablet is better than anything we currently have. The aim of this project is to scientifically develop the best shape and concentration of the tablet and then scale this up for human use and benefit.

This is being carried out by research groups at UCL Ophthalmology and the London School of Pharmacy, two groups with a world-class track record for developing new treatments. They are part of the new National Institute for Health Research Biomedical Research Centre which has been established to ?fast track? developments like this rapidly though to patient benefit and include the new NHS Pharmaceutical production facility at Moorfields Eye Hospital.

If successful, this new single tablet has the potential to considerably improve the treatment of glaucoma all over the world with fewer visits to clinic and prevention of blindness. There is great potential to improve the treatment of other diseases of the eye including macular degeneration, diabetic retinopathy, retinal detachment, blinding retinopathy of premature children and other scarring problems in the human body.

Technical Summary

The causes of fibrosis are complex and contribute to many human diseases, including every major blinding disease. There is a large unmet need for anti-scarring therapies; with at least 42 million procedures in 2004 which could have benefited from anti-scarring products. Administration of cytotoxic agents directly into the eye after surgery to control fibrosis to manage healing is currently the best clinical treatment available. There are many side effects because repeat injections of high doses that rapidly clear are toxic locally and systemically. There is a need to control fibrosis both generally and in the eye after surgery as there are no licensed treatments.

We have solved two major problems of current anti-fibrotic treatments: (1) To address toxicity, we have discovered that repeat injections of a metalloprotease (MMP) inhibitor have a markedly beneficial effect on scarring reduction without the toxicity of cytotoxic agents. (2) To address tissue specific pharmacokinetics, we developed a novel, small, resorbable tissue-tablet to release the MMP inhibitor locally at the fibrotic site. Using a clinically validated in vivo model, prolonged release profiles are achieved with a 100% surgical success rate to date. Preliminary results support a clear pathway to develop the MMP tablet to treat post-surgical fibrosis.

Publications

10 25 50
 
Description 2013 International Review Panel for the Centre for Eye Research Australia (CERA)
Geographic Reach Australia 
Policy Influence Type Participation in a advisory committee
URL http://www.cera.org.au/
 
Description EU Vision Institute meeting for the European Parliament
Geographic Reach Asia 
Policy Influence Type Participation in advisory committee
 
Description Healthcare and Life Sciences Global Business Summit
Geographic Reach National 
Policy Influence Type Participation in a national consultation
 
Description House of Lords Science & Technology Committee on Regenerative Medicine (2012)
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description NEI Audacious Goals
Geographic Reach North America 
Policy Influence Type Participation in advisory committee
 
Description Presentation to Earl Howe, Undersecretary of State for Health, NIHR
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
 
Description ARVO Travel Grant for Richard MH Lee
Amount $1,100 (USD)
Organisation Association for Research in Vision and Ophthalmology 
Sector Charity/Non Profit
Country United States
Start 05/2016 
End 05/2016
 
Description EP/I033270/1 EPSRC centre for innovative manufacturing in emergent macromolecular therapies
Amount £5,168,035 (GBP)
Funding ID EP/I033270/1 
Organisation Engineering and Physical Sciences Research Council (EPSRC) 
Sector Public
Country United Kingdom
Start 10/2011 
End 09/2016
 
Description Knowledge champions funding polymer drug delivery
Amount £50,000 (GBP)
Organisation UCL Business 
Sector Private
Country United Kingdom
Start 12/2011 
End 11/2012
 
Description Therapeutic Innovation Fund/UCL
Amount £50,000 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 09/2010 
End 09/2013
 
Title In vivo model (rabbit) of slow release tablet for the modulation of scarring 
Description Rabbit model of glaucoma filtration surgery developed. Model used to study the modulation of scarring after glaucoma filtration surgery, as well as to test the biocompatibility of materials developed for glaucoma devices. 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Provided To Others? No  
Impact Dialogue started with pharmaceutical companies 
 
Description Biocompatible coating 
Organisation Royal Free Hospital
Country United Kingdom 
Sector Hospitals 
PI Contribution To better treat subconjunctival fibrosis after glaucoma filtration surgery we are examining how changes in surgery procedure and the therapeutic agents that are used are necessary. To aid development of new surgical devices that might be developed into combination devices that also deliver a drug, we have sought a biocompatible polymer.
Collaborator Contribution Access to a biocompatible polymer
Impact None yet
Start Year 2011
 
Description Vertellus PC Biomaterials 
Organisation Vertellus
Country United States 
Sector Private 
PI Contribution We work with Vertellus to develop biocompatible polymers and they are a co-applicant on our NIHR i4i Challenge award.
Collaborator Contribution Expertise and experience in pc polymers and biocompatible materials.
Impact Successfully applied together for NIHR i4i Challenge Award for the development of a novel glaucoma device.
Start Year 2012
 
Title Slow release anti-scarring tablet 
Description Currently being enhanced, supported by DPFS scheme and Therapeutic Innovation Fund 
Type Therapeutic Intervention - Surgery
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2010
Development Status Under active development/distribution
Impact Not yet 
 
Description "Thinking about Research in Ophthalmology Training" 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact With the number of ophthalmology trainees doing research decreasing every year, this meeting hoped to provide more clarity for those who might be interested with an exceptional array of speakers and where people could talk frankly about their experience of doing research. Feedback from the meeting was extremely positive.
Year(s) Of Engagement Activity 2017
URL https://www.ucl.ac.uk/ioo/events/2017/dec/thinking-research-ophthalmology-training
 
Description Canadian Ophthalmology Society Invited Speaker 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Gave 3 talks at the conference in Halifax, Canada: "Advances in the management of childhood glaucoma", "Optimising glaucoma filtration surgery in children" and "Optimizing glaucoma filtration surgery".

Dissemination of information amongst peers.
Year(s) Of Engagement Activity 2014
URL http://www.cos-sco.ca/cpd/education/annual-meeting/
 
Description European Glaucoma Society Keynote Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact 100s of attendees. Held in Nice in 2014. Also gave two other talks on "Maximising success and minimsing complications in paediatric GFS" and "A glance into the future: New delivery systems"

http://www.eugs.org/
Year(s) Of Engagement Activity 2014
 
Description First Royal College of Ophthalmologists Public Engagement Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 'The Eyes are windows to our future'
Find out how research into the human visual system is helping to save our most precious sense
Description: When asked, people will say that eyesight is their most precious sense. But most people will not understand how complex and vital their eyesight is until things start changing.
As a highly social species, we use all our senses to interact with others. But sight is one of the most effective and useful in our ability to observe and navigate our surroundings, discern attitudes by facial expressions and body language, colours, light and shade.
Professor Khaw will take audiences through an extraordinary journey of the science behind our eyes, from how the visual system takes up more space in our brain than all other senses combined, to how it uses more than 10% of our body's energy with some retina cells consuming more than heart cells.
As the population ages, it is important that research continues to play a vital role in eye disease management. Professor Khaw will talk further about how research, advances in gene therapy and the use of microdevices, less than a millimetre in width, are helping to treat eye disease.
Year(s) Of Engagement Activity 2018
URL https://www.rcophth.ac.uk/christmas-lecture/
 
Description Four Liveries' Lecture on behalf of the Spectacle Makers' Company 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Talk on 'Stopping Scarring Saves Sight - How New Treatments to Prevent Scarring can Save and Restore Vision'

What glaucoma is, the problems faced and what we are doing to combat glaucoma with research and innovations.
Year(s) Of Engagement Activity 2011
 
Description Gave presentation to Moorfields Eye Charity Employees 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Other audiences
Results and Impact The Moorfields Eye Charity has expanded considerably over the last few years. Sir Peng was asked to give this talk to staff to to enthuse and educate them on why their job is so important and how they can have an impact on the pioneering work carried out at Moorfields Eye Hospital.
Year(s) Of Engagement Activity 2018
URL https://www.moorfieldseyecharity.org.uk/
 
Description Gave talk at 49th Cambridge Ophthalmological Symposium titled ' Conjunctival Fibrosis' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Delivered talk and 15min Q&A
Year(s) Of Engagement Activity 2019
 
Description Gave talk at 49th Cambridge Ophthalmological Symposium, titled 'New therapeutics in fibrosis control'? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Delivered talk and 15min Q&A session
Year(s) Of Engagement Activity 2019
 
Description Glaucoma Patient Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact 300 people attended

Dissemination of information on current research practices and innovations. Listening to what patients wanted and what was important to them.
Year(s) Of Engagement Activity 2011
 
Description Glaucoma Patient Day 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Small break out groups led by researchers addressed questions and sought patients' views on what they felt was important to them in terms of the type of research being carried out to help combat eye disease.

Dissemination of information in relation to they type of research carried out. Exercise to establish what patients want.
Year(s) Of Engagement Activity 2014
 
Description Hosted Blinded Veterans Association (USA) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Supporters
Results and Impact U.S.A. Blinded Veterans come together with their British counterparts regularly as part of the Project Gemini exchange programme. "The goal of the exchange is to learn from one another and share best practices in the areas of managing eye injuries received in combat, blind rehabilitation and vision research advances." The British Association hosted the USA in May 2018 and one of the meetings requested during their time in the UK was a visit to Moorfields Eye Hospital and the UCL Institute of Ophthalmology.
Year(s) Of Engagement Activity 2018
URL http://www.bva.org/BVA/News_Events/News_Archives/2017_News/May_2017_News/05_18_2017.aspx?WebsiteKey=...
 
Description House of Lords Science & Technology Committee (2012) 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Meeting transcribed and recorded to be available online on parliament.tv to be viewed by the public. Answered questions from the public.

Public made aware of the advancements and impact translational drug delivery.
Year(s) Of Engagement Activity 2012
 
Description International Council of Ophthalmology DocMode online course 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact This module is divided into 7 topics. The topic we contributed to was 'How to diagnose and treat POAG?'
Objective of the course: To be able to Diagnose and Treat Primary Open Angle Glaucoma

DocMode is an online platform that provides comprehensive and interactive learning programs for Health Professionals - Doctors, Nurses, Allied and Medical Students - across the world.
Year(s) Of Engagement Activity 2018
URL https://docmode.org/courses/course-v1:ICO+ICO001+2017_Nov_ICO001/about
 
Description Keynote Speaker, Academy of Medical Sciences Conference 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Talk on 'Opportunities in Academic Medicine'
27 November 2009
Victoria Park Plaza Hotel, London

Aimed at young doctors to enthuse them into research to consider a careers as a clinician scientist.
Year(s) Of Engagement Activity 2009
 
Description London Deanery School of Ophthalmology Conference (2012) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Health professionals
Results and Impact Talk on 'Academic ophthalmology: A career choice'
21 March 2012
Holborn Bars

Talk to inspire the next generation to consider a career in research
Year(s) Of Engagement Activity 2012
 
Description Presentation to the public for Glaucoma & Me Day: Look to the Future. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Talk on 'Look to the future'
10 July 2012
Royal Society of Medicine


Great involvement with the public and dissemination of information on why research matters and the advances being made.
Year(s) Of Engagement Activity 2012
 
Description President, UK Paediatric Glaucoma Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact Talk and discussions with both national and international peers to discuss paediatric management of glaucoma.

Have been given the opportunity of hosting the meeting in the US so that more US colleagues can attend.
Year(s) Of Engagement Activity 2013
 
Description RCOphth New Frontiers in Management of Glaucoma Seminar 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact 16 September 2013 at the Institute of Physics in London. Talk "Translating research into new glaucoma treatments".

Dissemination of information particularly how research can help with new and fast tracked treatments for diseases and how important it is that research continues and translation from the lab to clinic is as fast as possible.
Year(s) Of Engagement Activity 2013
 
Description RNIB Board of Trustees 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Presentation to the Board of Trustees of the RNIB.
29 November 2012


To provide information on current research initiatives and projects to hopefully forge greater collaboration.
Year(s) Of Engagement Activity 2012
 
Description Royal College of Ophthalmologists Admissions Ceremony 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact To enthuse new members

Dissemination of information
Year(s) Of Engagement Activity 2014
URL http://www.rcophth.ac.uk/page.asp?section=601§ionTitle=Admission+Ceremony
 
Description SENSORY SYSTEMS: FORGING NEW PARTNERSHIPS BETWEEN ACADEMIA AND INDUSTRY 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach National
Primary Audience
Results and Impact 11 November 2013 at the Institute of Physics, London. Participants included peers, colleagues and people from Industry with talks from scientists to showcase new and existing partnerships in industry and how we could all work to together even more to try and find cures.

Good networking opportunity with collaborators and industry to try and forge new links for working together on projects.
Year(s) Of Engagement Activity 2013
 
Description Talk to lay membership of Moorfields NHS Foundation Trust 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Public/other audiences
Results and Impact Attended by several hindred members. Interest in the reseacrh expressed afterwards.

Incresed levels of awareness of research and new developments leading to improved clinical care and treatment.
Year(s) Of Engagement Activity 2010
 
Description Talk to trainees & consultants at the North Thames Regional Study Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach Regional
Primary Audience Health professionals
Results and Impact Talk on 'Meeting unmet needs in glaucoma - A future look'
22 June 2012
London School of Hygiene and Tropical Medicine

The importance of academic ophthalmology and future research.
Year(s) Of Engagement Activity 2012
 
Description The International Agency for the Prevention of Blindness (IAPB) Glaucoma Week Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact This was an important way of reaching a spectrum of people working in or affected by glaucoma. The IAPB streamed the live talk across the world.

Summary of talk:
Glaucoma is the major cause of irreversible blindness around the world, and the numbers are projected to increase exponentially in both the developed and developing world. Research and new innovative approaches from rapid assessment to novel therapies will be required to prevent unnecessary blindness from glaucoma worldwide in the next few decades."
Year(s) Of Engagement Activity 2019
URL https://www.iapb.org/advocacy/world-glaucoma-week-2019/focus-on-glaucoma-lecture/
 
Description World Ophthalmological Congress 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact 100s of attendance. Held in Tokyo. 'Glaucoma: Repair and Regeneration from the Front to the Back of the Eye', 'Modulating Wound Healing'and "Prospects for Optic Nerve Repair and Regeneration"

Dissemination of information amongst peers. One of the talks was for the Royal College of Ophthalmology Symposium which showcased, UK research.
Year(s) Of Engagement Activity 2014
URL http://www.woc2014.org/