The Fifth International AKU Workshop

The next International AKU Workshop will take place this year in Liverpool. The Science Day will be on Friday 18th November followed by the Doctor-Patient Day on Saturday 19th November at the Liverpool Medical Institution (www.lmi.org.uk).

Topics for the Science Day will include:

• Building clinical trials for AKU using a disease severity score index
• Nitisinone, from weed killer to wonder drug
• Metabolomic investigation in AKU and OA
• Enzyme replacement therapy for AKU
• Gene therapy for AKU
• Novel biomarkers of cartilage and bone for AKU
• And more!

The Doctor-Patient Day will focus on topics such as:

• The new AKU Online Community, developed with the European Organisation for Rare Diseases (Eurordis).
• Stories from AKU patients about living with the disease.
• A demonstration of new physiotherapy techniques for AKU.
• Genetic counselling for AKU.
• Lay explanations of the latest progress in AKU research.

Speakers will include scientists (University of Liverpool, Imperial College, University of Siena), clinicians (Slovakia AKU Centre, Liverpool Hospital, National Institutes of Health), industry (Agilent, Protein Technologies Ltd, Nordic Biosciences) and patient groups (AKU Society, etc). At the previous International AKU Workshop in Cambridge, more than 70 people attended from 10 countries from North America, Europe and the Middle East.

To book, please contact booking@akusociety.org.

 

We’ve launched a partnership to develop a new enzyme replacement therapy

We’re really pleased to say that the AKU Society has launched a partnership with Protein Technologies Ltd, a bio-tech start-up, to develop a new model of enzyme replacement therapy for AKU that could have positive implications for many other rare diseases.

In the first of a series of studies, Protein Technologies Ltd will be producing a range of recombinant mutants of homogentisate 1,2-dioxygenase (HGD  – the deficient enzyme in AKU) and test them in vitro and in vivo in mice models for their effects on homogentisic acid (the damaging substance in AKU). Using site-directed mutagenesis techniques and its proprietary unnatural protein technology, Protein Technologies Ltd will seek to prove that a recombinant HGD can be synthesized which is more active and more stable than the naturally occurring enzyme.

This work will be in close collaboration with our scientific team at the University of Liverpool. We’re extremely excited about this project. If successful, it will open up a new avenue of potential treatment not just for AKU, but for a wide range of other rare diseases caused by deficient enzymes.

For more about Protein Technologies Ltd, read this article entitled “Project ‘could be as revolutionary as silicon chip’”: http://menmedia.co.uk/manchestereveningnews/news/business/s/1408919_project_could_be_as_revolutionary_as_silicon_chip.

Here’s what the enzyme, homogentisate 1,2-dioxygenase (HGD), looks like:

HGD enzyme

 

This is very exciting work for us. More than 65 mutations in the homogentisate oxidase enzyme (HGO) gene have been identified in people with AKU. It is widely believed that these mutations result in disruption of the structure and function of the HGO enzyme, thereby increasing the levels of homogentisic acid, which is the molecule causing the damage in AKU.

HGO is expressed mainly in the liver and kidneys. A promising strategy for the treatment of AKU is therefore administration of a recombinant version of HGO that can restore HGA to normal levels. Such a recombinant HDO analogue must be active enough to break down HGA but not so active as to bring about tyrosinemia (i.e. high levels of tyrosine in the blood). Longevity of action is also important as is the route of administration which, in addition to injection or nano-needle array, could also potentially include include oral, topical and inhalation.

 

The importance of fundraising

Sounds like a silly title – the importance of fundraising. Obviously, fundraising is important. Without money, there’s not that much we can do.

But fundraising plays a purpose for rare disease patient groups (and most other charities) that goes beyond raising funds. It’s about raising awareness, telling others about the issue you’re focusing on, using your supporters to spread the word.

This is something the AKU Society is increasingly trying to do. This Sunday, we have 10 runners taking part in the London 10k, a major sporting event with more than 25,000 runners participating and more than 40,000 spectators. It takes place in the middle of London and should be a fantastic event.

We got the idea from other rare disease patient groups. They encouraged us to register with the London 10k. One of these rare disease patient groups raises £25,000 a year thanks to the London 10k – that’s a substantial amount of funding that can be used as the charity wants in order to further its mission. I don’t think we’ll get anywhere near that amount this year, but it’s a good target to aim for in future years.

We do most of our fundraising for these events via our JustGiving page at www.justgiving.com/alkaptonuria. If you scroll down, you’ll see that there’s a whole bunch of supporters raising funds for us.

And if you’d like to sponsor me for the London 10k, you can donate on my justgiving fundraising page at: www.justgiving.com/Nicklondon10k. So dig deep!

Why patient groups should attend the Eurordis summer school

I’m just back from a terrific week of seminars at the Summer School for Clinical Trials for Rare Diseases, organised by Eurordis. There were around 50 participants from a range of rare disease patient groups from 20 countries across Europe. If you’ve never attended a Eurordis summer school, and you’re a patient group, then definitely keep an eye out for the next one.

The speakers were excellent, including members of the European Medicines Agency Scientific Advice Working Party, Committee for Orphan Medicinal Products, Committee for Human Medicinal Products and Committee for Advanced Therapies. We covered issues such as the life cycle of drug development (phase 1, 2 and 3 trials, etc), the theory behind randomised controlled trials and their applicability to rare diseases, the statistics of clinical trials, and the regulatory process.

We had group discussions on issues such as ethics and clinical trials, with case studies.  We also looked specifically at clinical trials in ‘non-standard situations’, which was particularly relevant to the small population sizes of rare diseases. We then looked at different forms of regulatory approval, such as marketing authorisation, conditional approval, and exceptional circumstances.

From our point of view, it was absolutely brilliant. The AKU Society and our partners are working on building a new clinical trial for a potential treatment, hence understanding the regulatory process is crucial to our success. The summer school provided a crash-course in all the key information needed to build a solid trial and go for regulatory approval.

If you’re interested in finding out more, go to the Eurordis e-learning website at: http://www.eurordis.org/content/e-learning.

 

Eurordis summer school on clinical trials for rare diseases

I got back late last night from London as we had a meeting with the NHS about our bid for setting up a National AKU Service in Liverpool. We’re cautiously optimistic as everyone seems to agree that the project is well put together and promising. It would make such a huge difference to the lives of AKU patients in England as they would have access to a centralised team of AKU specialists and treatments.

The plan is that AKU patients would be able to come to Liverpool each year for a full series of tests with a range of specialists (rheumatologists, metabolic consultants, physiotherapists, etc) to cover the range of health problems they face. If all goes well, the patients would also have access to the latest treatments.

More about all this in a later post as it’s still too early to tell whether the proposal will be approved.

I’m going to be away for the next week, probably without much blogging, as I’ve been invited to the Summer School on Clinical Trials for Rare Diseases organised by the European Organisation for Rare Diseases (EURORDIS). This is a crucial workshop as they will train 40 or so patient groups in all aspects of how clinical trials are set up, implemented and approved.

For the AKU Society, this is a major benefit as we’re already starting to plan new trials and applications to the European Commission for funding them. You can read all about the EURORDIS summer school here: http://www.eurordis.org/content/eurordis-summer-school-patient-advocates.

It’s non stop at the moment for the AKU Society. This week, Oliver Timmis, our AKU Communications Project Manager, was in Brussels for a workshop on how to apply to funding to the European Commission. Later this month we have the AKU meeting in Cardiff, which promises to be excellent.

Hopefully, we’ll be able to rest a bit in July!

 

Using social media for clinical research

Here’s an article article I’ve just come across from the Alzheimer Research Forum. It’s about using social media to carry out research into treatments: http://www.alzforum.org/new/detail.asp?id=2791.

The research team from PatientsLikeMe, an online medical data sharing platform, used data volunteered by patients on the site to evaluate the efficacy of off-label lithium use for amyotrophic lateral sclerosis (ALS), as discussed in the April 24 online Nature Biotechnology journal. ‘Because in 2008 a small clinical study suggested that lithium might slow disease progression, some ALS patients decided on their own to try the drug. PatientsLikeMe built a data collection tool where participants could enter information about their symptoms, treatment, and outcomes, using the Revised Functional Rating Scale to measure disease progression. After 12 months, 149 people who took the drug met inclusion and exclusion criteria for analysis.’

The analysis showed no significant treatment effect from lithium, which was in agreement with the findings of other, larger clinical trials, which suggests that the online registry approach for the study was useful. For the authors of the article, this confirms that online data-sharing registries may be useful complements to traditional clinical trials.

I agree. We need as much data as we can gather about diseases, and even more so for rare diseases. Building platforms that can capture such data in a reliable way is therefore crucial. More about this in subsequent posts as we progress with our plans for an online registry.

The challenge of being a small rare disease patient group

We’re moving office today. Our old office was in a place in Cambridge called the Social Enterprise Centre. The facilities were a bit run down, but it was a fun place to work, with lots of other small charities and budding businesses and a great sense of entrepreneurship. It was in a building earmarked for demolition. That’s why the social enterprise that ran it (called FutureBusiness) managed to get such a low rent for its tenants. The landlord was willing to rent it out for very cheap while he sorted out selling it.

So a couple of months ago we were given notice that they were going to demolish the building in order to build a hotel. FutureBusiness managed to find new office space in the top floor of a DIY warehouse. It’s temporary accommodation while they raise finance to build a brand new social enterprise centre in the north of Cambridge. We’re doing the move today, with one of our volunteers (an AKU patient) hiring a van and recruiting his sons to help us shift our stuff.

Why do I tell you this story? To show you some of the challenges facing rare disease patient groups. Like most other small charities, we have very little money and depend on the goodwill of others to find us affordable office accommodation and other resources. We depend on the work of volunteers, including dedicated AKU patients, to help us move forward.

And yet, the AKU Society is one of the more developed rare disease patient groups. Most other ones don’t even have an office or dedicated staff. How can we expect them to make a significant difference for their patients if they don’t have the resources to do so?

That’s why I’m convinced of the urgent need to build the capacity of the rare disease patient group sector. We need foundations that will support them with more than just a few hundred pounds. We need affordable training for their staff and volunteers. We need a concerted effort at organising patient groups and helping them interact with academia and industry.

A few of us are getting together over the coming months to see what we can do. If you’re interested, drop me an email at nick@akusociety.org.

Patient registries at the World Orphan Drug Summit

I’m just about to leave for Frankfurt, Germany, to participate in the World Orphan Drug Summit. I’ve been invited to help facilitate a workshop on patient registries on Monday afternoon, led by CheckOrphan. It’s going to be an opportunity to discuss many of the issues we tackled in our application to the EC (see yesterday’s post) and encourage businesses to think more creatively about how they build patient registries.

So why are patient registries so important? Basically, a registry is a database of patient information about their condition, their treatments, their health, etc. It allows the registry owner to track how well patients are doing and is particularly useful for clinical trials. Without data on patients, it’s impossible to prove that a treatment is working.

Unfortunately, many patient registries are way too complicated. Clinicians and patients find them difficult to fill in and they’re often clunky and hard to use. That’s why we’re looking at setting up a very user-friendly registry, with online access by patients and clinicians, with all the data then anonymised for clinical trials.

It’s very important for rare disease patient groups to develop registries, as these will give them access to significant data for then working with industry and academia on developing new treatments. I’ll be publishing more about this in subsequent posts.

Plans for an EU-registry for AKU patients

OK – I’ve now submitted our proposal to the European Commission’s Executive Agency for Health and Consumers. We’ll hear by autumn whether it’s been successful. It’s highly competitive, although I’m cautiously optimistic because I think we’ve done a terrific job. The aim is to build an EU-wide network for AKU, based on our existing partners, but also identifying new ones, then to build an EU registry for AKU patients and an online reference network for AKU clinicians to share information about the disease and agree on common treatment guidelines.

If we get the funding, AKU Information Centres based in France, UK, Italy and Slovakia will develop simple mechanisms with health professionals to identify people with AKU, direct them into appropriate treatment and support and develop cooperation on AKU. They will start working in their own countries, and then extend to neighbouring countries.

Our AKU EU Coordination Centre, hosted in the UK, will coordinate the project. We will email patient identification questionnaires and information packs about AKU to a list of all doctors and medical specialists, helping with diagnosis, treatment and care. We will send information to people affected by AKU and their families/carers. We will set up a European network of AKU helplines/email systems. We will set up an EU register of people with AKU. We will develop the online registry into a virtual European AKU reference centre, with care and treatment guidelines and exchange of information. It’s all based on the successful pilot project we did in the UK in 2007-08.

Here are the expected outcomes by the end of the project:

• To set up an EU Information Network for AKU and identify up to 600 new patients in the EU.
• To set up an online registry and collect data on up to 1000 AKU patients (new and existing ones) in the EU.
• To set up a virtual EU Reference Network for AKU that shares information and expertise in order to improve overall quality and management of care for AKU across Europe.

I’ll let you know as soon as we hear back from the European Commission.

A great AKU symposium

We had a terrific two days in Liverpool on Thursday and Friday last week. Adam Taylor, who we funded through his PhD for the past 3.5 years, had his viva on the Thursday. He started with a lecture about his research to a group of 30 or so people. It was fascinating and showed just how much he accomplished in that time. He then had his 3 hour assessment with two supervisors and came out with flying colours. We were thoroughly impressed.

On the Friday, we did a mini symposium with world class speakers. Prof Virginia Kraus, president of the Osteoarthritis Research Society International, presented her latest research into osteoarthritis and made links with AKU. Dr Ranganath, our Medical Director, did a presentation on AKU. Dr Melinda Duer from Cambridge University explained about her research using solid state NMR. Dr Peter Clegg from the University of Liverpool  then talked abuot ‘osteoarthritis in athletes – lessons from a naturally occurring horse model.’

So we came back very inspired by how things are progressing.

Yesterday, however, was a slightly different matter as I spent the whole day working on our upcoming application to the European Commission for funding to set up a European registry and information/reference network for AKU. They sure know how to design long forms… However, I’m pleased to say that the application is nearly done. Just a few finishing touches.