Rare disease awareness: Alkaptonuria

Oliver Timmis

AKU Society

As part of our rare disease focus month we interview Oliver Timmis of the AKU society on how we can increase recognition of rare diseases such as AKU.

There are approximately 7000 rare diseases and many patients suffering from them unfortunately face years of misdiagnosis and are left feeling isolated and marginalised.

As part of our rare disease month we speak with Oliver Timmis of the AKU society, on how we can raise awareness of these disorders and help reduce patient isolation in these cases.

Interview summary

RA: Oliver, thank you for agreeing to take part in this interview, could you please start by explaining your background and how you came to be in your current role.

OT: I’m the Communications Manager for the AKU Society, where my main role involves keeping the scientific researchers in contact with AKU patients. We find this useful as it reminds the science and clinical teams why they need to understand and cure the disease, and it gives patients hope for the future. I’ve represented the society at national and international levels, as a member of the Genetic Alliance UK, Specialised Healthcare Alliance, EURORDIS and the advisory group to the UK Genetic Testing Network.


“Most of the large research-funding bodies in the UK have no clear plan for rare diseases.”

RA: What is Alkaptonuria and how does it affect patients?

OT: Alkaptonuria (AKU) is a rare genetic disease that causes early-onset, severe osteoarthritis. It was discovered more than 100 years ago, by a brilliant doctor called Sir Archibald Garrod, but still has no cure. AKU is present from birth, identified by the urine of babies turning dark when left to stand in air. By their late 20s / early 30s, patients start to develop back and joint pain. They tend to get black spots appear in the whites of their eyes, and their ears will darken as the cartilage underneath pigments. The pigmentation is due to the accumulation of a chemical called HGA (homogentisic acid) that binds to bones and cartilage turning it black and brittle. Eventually the cartilage breaks away, exposing the bone underneath and causing painful osteoarthritis. At the moment, the only widely-available options for treatment are pain relief and joint replacement surgery. AKU will also cause stones to form in the kidney and prostate, as well as increase the chances of developing heart disease.

RA: What have been the latest therapeutic advances in this area?

OT: We’ve just opened a new treatment centre, based at the Royal Liverpool University Hospital, and funded by the Department of Health. It will offer annual clinics to every patient in the UK and give them a great opportunity to track their own disease. The centre can also prescribe a new drug, called nitisinone. Nitisinone, produced by Swedish Orphan Biovitrum (Sobi), is not licensed for AKU, but since it’s licensed for another disease (tyrosinaemia), it can be used in the UK off-label. The centre is going to be tracking its usage in patients, and we’re building up to a phase III international clinical trial of the drug to start next year. While it’s still experimental, it looks to be the best hope for AKU patients. The AKU Society is also funding research into other forms of treatment, including a protein replacement project with Protein Technologies, an SME in Manchester and a gene therapy project with Imperial College London. Both of these ideas are still in very early stages and so, if successful, wouldn’t see human benefit for several years.


“Most of the large research-funding bodies in the UK have no clear plan for rare diseases.”

RA: What can be done to increase support for rare disease patient groups?

OT: Funding is a problem. Most of the large research-funding bodies in the UK have no clear plan for rare diseases. Even though 8% of the population have one of 7000 rare diseases, they just don’t see it as a priority. Without the means to allow rare disease groups to develop and grow, they can never professionalise and reach a point where we can make a significant difference. I’d like to see the strategy for the traditional funders to change to reflect an approach more similar to venture philanthropy, whereby funders spend more time on the due diligence: meeting the team, assessing their track record, discussing their strategy. And once they’ve found a team of A-players, they support it over a long period of time. Not a one- or even a three-year grant, but sometimes up to 10 years or more. Venture philanthropists know that persistence and commitment pays off.

RA: How can we reduce the marginalisation and isolation of rare disease patients?

OT: A key part of this is simply making sure that people are made aware of rare diseases. There’s a great example from the world of cancer research, where the University of Nottingham have shown that minority ethnic communities are severely underrepresented in all cancer treatments. It’s not that they don’t get cancer – in fact, Afro-Caribbean men are three times more likely than men from other backgrounds to develop prostate cancer – but that many minority communities treat cancer with a stigma. No-one talks about cancer, and anyone with cancer will hide the diagnosis. This is an extreme example, but similar to rare diseases. If no-one talks about them, then the scale of the problem is largely ignored. As a patient group, it’s our role to raise awareness.


“A lot of the problem is due to a lack of knowledge of rare diseases.”

RA: How can we raise awareness of the disease?

OT: One of the main tasks of the AKU Society is to find all patients with the disease so that we can offer support. In the UK, the most effective way of doing this was to run a patient identification campaign, by posting letters to every GP in the country. Back in 2007, that was 11,151 surgeries and thanks to a grant from the Big Lottery Fund, we contacted them all. It led to us increasing the number of AKU patients we knew from 4 to 81 and allowed us to form a much stronger network. To increase awareness among the general public or even the general medical professional is much harder. We attend many doctors conference and try to talk to as many people as possible, and occasionally it pays off and helps to identify a new patient, or a new research angle. However it’s slow and inconsistent. There needs to be a mass movement, along the lines of the events by Cancer Research UK. Groups such as the Genetic Alliance in the UK and EURORDIS in Europe have made great headway, but there’s still a long way to go.

RA: How can more accurate diagnoses be reached in patients with rare diseases?

OT: A lot of the problem is due to a lack of knowledge of rare diseases. There are more than 7000 so we cannot expect every doctor to know each one expertly, but I think more emphasis should be placed on spotting the patients that don’t quite fit into the normal common diseases. AKU is often mistaken for osteoarthritis and they are similar diseases. However, there are difference, AKU patients develop joint pain earlier in life, and will have other symptoms like the dark ears, black spots in the eyes, and maybe heart disease or a kidney stone. If more questions were asked when a patient has unusual symptoms for a common disease diagnosis, then I think fewer patients would face the years of misdiagnosis that are unfortunately common in rare diseases.

RA: Can you tell me more about the AKU Society?

OT: The AKU Society was founded in 2003 in Liverpool by a patient and his doctor. We often use the medical / patient partnership as a great example of how we try to involve both groups in all our work. Our latest big funding application was to the European Commission for 6 million Euros to run the nitisinone clinical trial. It couldn’t have been done without our well-developed network of clinicians, scientists, industry and other AKU patient groups.


“…more emphasis should be placed on spotting the patients that don’t quite fit into the normal common diseases.”

RA: How can research into rare diseases be applicable to more common and larger disease areas?

OT: Many rare diseases are seen to be extreme forms of a common disease. AKU is a more severe and earlier type of osteoarthritis. Much of our basic research looks at this connection and has just led to the teams at Liverpool publishing a paper on new anatomical structures – trabecular excrescences – found in AKU bone and now, for the first time, in OA bone. By understanding the rare disease, it often leads to understanding the common disease. It’s been seen before, even as far back as 1657, when the surgeon, Dr William Harvey could find no better way to advance medicine that “by the careful investigation of cases of rarer forms of disease”.

RA: Can you tell me more about findacure?

OT: Building on the idea of using rare diseases to understand common diseases, findacure, is a new foundation that will identify fundamental diseases and provide funding for their research. Fundamental diseases are those with a credible link to a common disease. The foundation will have three main aims, to increase public awareness of fundamental diseases, to significantly increase patient groups’ capacity for work, and massively scale up research.


“Many rare diseases are seen to be extreme forms of a common disease.”

RA: Finally, what would your take home message to pharma be?

OT: To involve patients and patient groups. My experience has shown that a lot of pharma companies tend to avoid too much interaction. However, our experience through working with Sobi has led to a great partnership and the start of a clinical trial next year. I’d like to see more industry / patient collaboration as it should benefit both of us.

RA: Oliver, thank you for your insights.


About the interviewee:

Oliver has an Bachelor’s degree in Natural Sciences from Cambridge University, where he developed an interest in the public understanding of health sciences and so found the role at the AKU Society in science communication appealing. Since working here, he has seen the apparent inequality in rare diseases. They contribute a massive health problem, with millions of people in the UK suffering from diseases that most doctors have never heard of and have little hope for treatment. The scale of the problem is largely misunderstood and in an attempt to get some answers to the question why this is so, he is due to begin studying for a MSc in Health Policy at Imperial College London this October.

How can we raise awareness of rare diseases such as Alkaptonuria?