This year Rare Disease Day fell on that rarest of calendar days, the 29th of February. The NSPKU now hold their annual conference on the weekend closest to that special day and this happy combination meant that it was well beyond time for me to attend again. I had last attended a pre-Christmas conference as a child, and remember little beyond the Santa Claus. Sadly, I could only attend on the Saturday this year, but the line up was worth the early start.

This report covers the Saturday morning session which includes the latest research and legal wrangling on PKU. I hope to cover some of what was going on at the food stands and in the afternoon workshops soon.

Pioneers of the First PKU Diet

Professor Anne Green, Birmingham Children’s Hospital

Professor Anne Green opened proceedings by taking us back to Birmingham in 1948 when three pioneering doctors synthesised the first dietary treatment. It wasn’t known if a treatment was even possible and embarking on a low protein diet in the midst of post-war rationing was an epic challenge. As Professor Green noted, many things had to come together for the development of a treatment:

  • Mary Jones had to spot that there was a problem with her daughter Sheila.
  • Mary’s GP listened to her concerns and referred her on to…
  • The three doctors at Birmingham Children’s who were determined to find a solution.
  • Mary and her family had to trust in a new diet and find a way to stick to it in a time when food in England was a precious commodity.

This was a sobering tale, but also a hopeful one. If the diet had improved so much from it’s early days, there is surely hope that the treatments will get easier. This section segued neatly into our next speaker.

Medical Update & Treatment Options

Dr Radha Ramachandran, Consultant in Inherited Metabolic Disease, Guys & St Thomas’ NHS Foundation Trust

Dr Radha reported on new research into PKU treatments. As I noted above, this is hopeful but all treatments are in their early stages and little is know about if they will work or what the long term effects might be.

Gut absorption therapy in PKU

There are a few options being investigated which might absorb Phe (Phenylalanine) in the gut before it goes into to bloodstream. One option is using a safe version of Lactobacillus to carry PAH (Phenylalanine Hydroxylase, the enzyme which people with PKU are lacking) into the digestive tract. Another option being looked at is using a medical resin instead of bacteria. It is very early days for both methods and we just don't know if either approach is safe or if it will be effective.

Enzyme replacement therapy for PKU- Beyond Palynziq

This branch of research looks at using a substitute enzyme to help someone with PKU to metabolise Phe. I’ve written more about the background of why and how this works here. Currently there is an enzyme replacement therapy on the market in the US and EU called Palynziq which needs to be injected into the skin at least daily. Dr Radha spoke about the possibility of introducing engineered cells to the liver to deliver the replacement enzyme directly to the digestive system. Again this is very new, and one of the key questions is working out how long such liver cells might live and thus how effective any treatment might be.

PKU and gene therapy

The news that there is work on setting up a gene therapy trial in the UK caused quite a stir during Dr Radha’s talk. In very layman’s terms, this therapy would involve:

  1. Isolating a bit of a gene which corrects the production of PAH in someone with PKU
  2. Finding a (good!) virus to carry the gene safely and without changing it
  3. Finding a way to inject the virus carrier and gene into someone with PKU
  4. Directing the virus carrier to the correct place in the body for it to work
  5. Once there the gene segment starts to work, producing PAH and treating the PKU.

You can see why there was excitement about this therapy and potential trial. But, as always in science and research, there are many But’s. Ensuring that steps one to four can happen safely and reliably many times over is no easy task. I don’t pretend to know the in’s and out’s but reproducibility and safety are big assumptions here.

If the technology does reach the stage where these steps are sorted out, there are still many unknowns like:

  • Will it work?
  • What is the correct dose and does that dose differ between patients?
  • Does virus affect other organs?

The researchers do know that the immune system will react to the virus. So each patient can only receive this treatment once. It is key to remember that, while the expectation is of a life time cure, we currently have no idea if that will actually happen. So if this is injected into someone and it doesn’t work then their immune system will probably mean that trying again is not an option.

Side step - Kuvan.

Kuvan, or sapropterin, was the talk of the conference thanks to the launch of a Daily Express campaign to get funding for the drug on the NHS. This was an exciting development which has progressed quickly in the last week. There is now a petition to parliament for Kuvan to be funded on the NHS. At time of writing enough people have signed to ensure that the government will respond, though no response had yet been received. To sign the petition, click here

PKU and the Law

Peter Todd, Partner, Hodge Jones & Allen, Solicitors, London

“Peter Todd is a solicitor and partner of Hodge Jones & Allen Solicitors, London. He practises in the field of medical and public law, including cases about refusal by the NHS of funding for expensive medical treatments.” 1

Peter became involved in medical funding several years ago and the success for his client drew the eye of a PKU parent who enlisted his help for Kuvan funding. This conference segment was an illuminating walk through the legal wrangle about the commissioning of Kuvan on the NHS.

Slide from Peter Todd's presentation

From the slide above, Kuvan currently sits in the ‘Not routinely funded’ box. Peter has led the charge in challenging this through the court. This work has been laborious but there has been some success in challenging the method used for reaching the ‘Not routinely funded’ decision. Peter noted that Kuvan is effectively now in a battle for funding against other rare diseases. I couldn’t help thinking that we are competing in the hunger games

In good news, those with PKU who cannot maintain levels below 600 µmol/L may have a route to Kuvan through an Individual Funding Request. I hesitate to discuss that process here as it is involved. Possibly the best place for a query is Kate Leaoryd (https://twitter.com/PKUFamily) of the NSPKU.

I did ask Peter if there is any scope to question the 'levels above 600’ only access to treatment. However, that is the limit for brain damage which is currently widely accepted by the medical community so that is the level at which access to the new treatment is set. As was pointed out during the extensive Q&A session, this is a frustrating and slow process which can seem unfair. But, thanks to the efforts of people like Peter, progress is being made.

PKU and the Family

Angela Matthews (NSPKU Support Group Lead for Kent) and Friends

Angela had gathered together a panel which included adults with PKU, the parent of an adult with PKU and the parent of a newly diagnosed PKU child. Their discussion was a frank one which ranged from memories of growing up through frustration of daily life with PKU to the fears of a parent. Discussions such as these hinge on the participants and all who took part were candid in their experiences. The nature of the section means that it is not easy to discuss here, but one outcome was agreed on by all:
Having a community around you really helps with PKU.

Whether it be a network ‘in real life’ (IRL) or online, having people who know what it is like to grow up with or along side someone with PKU is important. The fact that this is such a rare diesase means that finding people ‘IRL’ can be difficult. So if you are looking for a PKU community the best place to start may be online at:

https://www.facebook.com/groups/nspku or following @NSPKU and others with PKU on Twitter - like me!

I must finish by saying that being a part of the PKU community on social media has proven invaluable. Sometimes just having someone say ‘I get that too!’ is so encouraging. It was great to meet some of the online pals at the conference and I’m already looking forward to next year.

  1. NSPKU Conference 2020 - Programme Abstracts. http://www.nspku.org/publications/publication/47th-annual-conference-2020-programme-abstracts. Accessed March 2020. ↩︎