AGSD-UK helps fund Rotterdam group

The UK Pompe patients, organised within the AGSD-UK, had a clear goal. We wanted to raise funds and raise awareness, in order to help the Rotterdam group take their work on ERT forward.

In 1996, there was an opportunity to do exactly that.

The problem for the Dutch group (I am putting words into their mouths here, for which I apologise) was to find a way to make the jump from their ground-breaking experiments that demonstrated that ERT could work in principle, to clinical trials. The funding required for that (£ millions) seemed like an insurmountable problem, however they took the sensible approach of taking one small step at a time. For example,  a collaboration with John Hopwood's lab in Australia had resulted in the development of cells which produced alpha-glucosidase (complete with the critical sugar residues attached) and which were suitable for growing in a production vessel.

The strategy was therefore to use the Hopwood cell line to produce enough alpha-glucosidase to treat one or two patients and hope that a pharmaceutical company would then take it up. This was, to say the least, an approach fraught with uncertainty. However it is also true to say that there was no alternative.

To produce the enzyme, it was proposed to use a new company started by a former student (Martin van der Vliet) of Arnold Reuser's, called Biocell technology, who would build a small-scale fermenter. However this work, while being done at a bargain rate, still needed funding- and, despite applications to grant-awarding bodies and biotechnology companies, none was forthcoming.  That was where the AGSD-UK were able to step in and fund the building of the fermenter via a grant of £10,000. Here's a photo of it below (that's the old AGSD-UK logo in the corner):

This was a great day for the UK Pompe patients - at last we were taking an active part in shaping our own destiny. At the same time, the AMDA were funding similar work at Y T Chen's lab in the US (along with other projects).

I think that the AMDA had also offered to fund the Rotterdam work, however Arnold Reuser and Ans van der Ploeg opted to receive the money from the AGSD-UK instead, a route that involved them in a bit more hoop-jumping. Why? I don't know for sure but here are my guesses. Firstly, they knew how much it would mean to us to do it. Secondly, it always makes sense to keep a diverse range of funding options open - and they knew that the AMDA route would still be open to them in the future. Thirdly - and this is a complete guess on my part - Arnold had a shrewd idea that by allowing us to become a funder, it would give us a seat in future discussions on the development of ERT.

£10,000 is, of course, in the grand scheme of things a small amount (though it represented a lot of hard work and generosity by many people). However, I believe that it had an effect out of all proportion to the amount. Again, I am departing into the realm of conjecture here - what follows represents my opinion only and I am not going to present any evidence to back it up:-)

The reactor was indeed used to produce enzyme that was used in experimental work. However it also demonstrated to Erasmus University (and Sophia Children's Hospital) that the Pompe group were capable of raising funds from overseas to further their work. I think that would have helped to boost their profile.  Most important of all, the Rotterdam group had been in discussions with a biotech company called Pharming, regarding the production of alpha-glucosidase in the milk of transgenic animals. These discussions had been going on for a while and were inconclusive. However the advent of a new funding source (conveniently omitting that it was a small charity with limited resources) may have helped to push Pharming into a decision to commit to the project. It's a great theory - but I have absolutely no idea if it's true!

Soon after, Pharming did indeed commit to the Pompe project. And that decision was the key to making things happen.

1996

A quick summary of where we were at in 1996.

In retrospect, this was a pivotal year though it didn't seem so at the time. The patient group in the UK was growing slowly. The Pompe's Bulletin newletter was circulated to any patients, doctors and scientists that we could think of. The patient groups in different countries  began to reach out to each other via the internet.  Another common link was Arnold Reuser's group on Rotterdam - their willingness to engage with the growing patient community was crucial to its development. They struck a careful balance between their compassion and their professionalism.   There was a growing sense of beginning to come together for a common purpose. Little did we know that things were about to kick off in a quite astonishing way. But that's for 1997:-) First a couple of articles on 1996.

House improvements

I have tried to make this a roughly chronological account but I'm going to go off piste here because I can't give a good portrait of Randall and Marylyn without looking ahead.

In front of me is my first  written communication from the Houses. Dated 29 August, 1995, it expresses sympathy for our loss of Calum, introduces Randall, Marylyn and their daughter Tiffany (then just a 12-year-old slip of a girl) who has Pompe (they have two other children, who do not), shares their conclusions so far and a sheaf of information on diet, including a paper by Pompe patient Donald Ewers. In hindsight it has all the hallmarks that mark out the Houses: compassion for others, sharp analysis and - above all - a drive to translate those things into action. It's a bit of a cliché but I found a lot of the American pioneer spirit in the Houses.

We talked on the phone and exchanged emails and gradually built up a relationship. My dealings were mainly with Randall, whose no-nonsense approach impressed me. We were fairly guarded with each other at first, as we worked out each other's agendas. It's probably true to say that I respected Randall before I liked him - though I came to like him a great deal. He is straight-talking - not given to exaggeration or soft-soaping. I found that if he said something, he meant it and if he said he would do something, he did it.  I quickly realised that the Houses' resources were in a different league and that the most useful thing I could do was to be as open as possible and hope that it was reciprocated (it was).

Randall's words to me were along the lines of "We are not super-wealthy but we do have some means. We would like to use that means to find a treatment for this disease." Little did I realise then how much they would do. I also didn't fully appreciate at the time what those words meant. The Houses owned (still do, I think) a manufacturing business that they had devoted years to building up. That "some means" came from hard work and toil. I think it was, to a significant extent, their life's work up to that point. And yet they unhesitatingly put it at the service of finding a treatment for Pompe disease. In my view, their contribution to the development of a treatment for Pompe disease is as much their life's work as building their successful business.

I think I suggested that to have maximum effect they should found a patient organisation (the AGSD-US was, for whatever reason, less amenable to a devolved Pompe group than the UK version) , rather than act as individuals, and also have a scientific advisory board, to ensure that their money was spent wisely. We were both agreed that enzyme replacement therapy was the way to go.  I don't know whether I had any actual influence, however Randall and Marylyn founded the Acid Maltase Deficiency Association (AMDA) as a patient organisation.  They used that as their base to do some remarkable things.

Firstly, they built the AMDA as a source of advice and information for hundreds of people affected by Pompe disease. Secondly, they did something that had never been done before. They gathered together, at their own personal expense, Pompe experts from all over the globe and hosted a conference for them in San Antonio, Texas. This was on March 21-22, 1996. The talks read like a who's who of the Pompe world. It was followed by a second, even bigger, conference on June 22-23, 1997.

Organising these conferences was an imaginative and  far-sighted act. As important, I think, as the funding that the Houses put into research (again, a significant amount - nearly $5 million to date, according to the AMDA website). They were obviously scientific conferences, not patient ones, however the Houses were kind enough to send me video recordings of each conference, which allowed me to keep right up to date with what was happening. A characteristic piece of generosity on their part.

Looking at the 1996 programme now, I am amused to note that the session started at 7.00 am with breakfast and registration. That's approximately 2.5 hours earlier than most scientists are used to, so I guess Randall and Marylyn were putting their own work ethic stamp on proceedings from the start (1997 had a more leisurely 7.30 am start). The programme was designed by one Tiffany Laurel House, who now heads up the AMDA.

In the founding of the AMDA and the gathering of US patients together, and bringing together scientists, Randall and Marylyn were playing the major role in creating a worldwide Pompe community. In extending those connections to industry (I'm really getting ahead of myself now) they helped found a new model in the development of treatments for rare diseases, one in which patients, researchers, doctors and companies interact. The development of ERT for Pompe was possibly the first instance where an informed patient community said to industry, in effect, "We are your future customers, this is our condition and this is the treatment we would like you to develop." But more of that later.

For now, it's enough to say that Randall and Marylyn  changed the game. In a very real sense, they made ERT happen. They made it happen while being part of an international community. And they made it happen not just for Tiffany but for all Pompe patients.

Postscript
I don't think I actually met Randall until 1997, at the AGSD-UK's annual conference. Here's my earliest memory of him. We had introduced ourselves and I noted that he was wearing a formal business suit, unlike my scruffy self. I was fussing about trying to make some sense of the organisation of the Pompe session out of the customary AGSD-UK chaos. There was a group of parents who had found some space on the floor in order to feed/change their young children. Next time I turned around, Randall had hunkered down on the floor, amongst the crumbs, in his business suit, in order to talk with them. That's my abiding image of Randall House. Sorry, I can't tell you what brand of suit it was - or what kind of watch he was wearing.

Making connections

The UK group was definitely stirring and I had a growing mailing list that I could send paper newsletters to. However I realised that there were probably patient groups and individuals in other countries going through exactly the same process - but how could I contact them?*  The answer seems simple now - just use Google, d'oh!  Unfortunately, in 1995 Google was yet to be invented. I had internet access at work though and was keen on the idea of using a website as a sort of shop window.

A bit of history/nostalgia. My first web browser was something called Lynx which was entirely text-based. I then started using something called Mosaic which had the startling innovation of allowing you to see pictures and text. I got a hold of it by email - you got sent the code for it in chunks and had to manually piece them together to make a functioning piece of software. Happy days.  But I digress.

I put together a rudimentary website for the AGSD-UK and included the full text of my Pompe patients' guide.  A friend at work kindly hosted on his webspace (cheers, David). But how could people find it? I emailed it around to anyone I could think of but there were no search engines as such. However a couple of students at Stanford University had used their university account to set up a sort of index for interesting websites, so I listed it there. They had called their site Yahoo. It'll never catch on with a name like that, I thought.

Anyways, I gradually made contact with people from other countries - individuals from Germany and the US to begin with. Then I got a phone call from a guy in the USA that I'd never heard of but who had come to the same conclusions as me and was determined to do something about them. His name was Randall House and he, along with his wife Marylyn, changed everything.

*I realise on looking through my papers that the original list of names I was given by Ann Philips contained one non-UK contact - Helen Walker from Australia. I'm surprised by that and also to find that I've now been in touch with Helen for 15 years! More about the Ozzies later.