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Extracts from John Forman's report to LDNZ Trustees on his trip to the MPS/Lysosomal conference in Mainz, Germany, in June 2004.

There were a lot of positive things coming out of this conference, in terms of contacts made and information gained, for the benefit of LDNZ and the families we support, and of interest in knowing what progress is being made towards therapy. However it was necessary to search these things out in a conference that seemed a bit confused in its programme, themes and multiple concurrent sessions.

The “negative” side of it could be summarised as follows:

1. A conference that tended to be narrowly focused on MPS rather than inclusive of all Lysosomal diseases. Very disappointing that it was organised this way, rather than the “inclusive” approach taken at the main international conferences over the past 5 years.
2.  A consequence of this approach was more limited scientific sessions on the “related diseases”, as well as big gaps from a family perspective in getting any coverage of these in the family oriented sessions. In my view the MPS societies are failing those affected by the related diseases with such a narrow approach, and I have begun telling them this more directly and openly as time goes by.
3.  Even within the MPS conditions there was, understandably, a predominance of information about those with emerging therapies, but this left families with the likes of Sanfilippo, with little in the programme for them.
4. The sessions run by the support groups focused on operational and “feel good” topics like how to raise money, how to get media impact, etc, but did not address key strategic issues such as screening and diagnostic services, supporting research, orphan drug development policies, drug payment policies of governments, etc. I spoke at the end of the support groups’ session to urge a more strategic approach to solving many of these key issues.

But in spite of the quibbles I have about these issues, there we many positive outcomes as well:

1. GOLD held its first AGM and was well supported by many groups from many countries. It was a brief and formal meeting to present accounts and a Trustees report, but I got a chance in general business to draw attention of about 50 people present, to the pressure from disability activist organisations towards a “no prevention of disability through pregnancy termination” policy, that has been strongly put to the UN special committee on the proposed Disability Rights convention. I am concerned that these activists claim to speak “on behalf of 600 million disabled people worldwide” but I know they do not have a mandate, nor do they reflect the views of most parents, especially those who have had one seriously disabled child, and would not like another with the same condition. I urged GOLD to make itself aware of this and to consider a response, though there might well be a reluctance on GOLD’s part to get involved in a controversial issue early in its development phase. I will continue to push this issue in my other health and disability networks.
2. A discussion with Thomas Braulke from Hamburg (I approached him because he presented on NCL and had Dave Palmer listed in his acknowledgements or references), led to the discovery that a member of his team, Stephan Tiede, has a particular interest in ML3. I met with Stephan and others in the team and discussed Jenny’s work on this condition, and ISMRD’s work to support research and family links for this condition. I also introduced them to David Sillence so they could discuss the trial with pamidronate, and consider future collaboration. David said it was useful to him to know of their interest as they, and Gideon Bach in Israel, seem to be the only group in Europe/Middle East with plans for research on ML3, and they are now well linked up.
3. I made contact with new support groups from Poland, Hungary, Ireland and Spain, and I will add these to the LDNZ directory of groups soon. The more of these groups we have in our network, the better chance we have of getting international collaboration around strategic issues, and effectively sharing information with families about symptom management and risks.
4. A very significant benefit of the informal discussions with other groups, came from discussing ERT funding with the British MPS society. This helped me appreciate some of the indications of ERT for “mild” Hurler disease, and the importance of this therapy in probably avoiding serious problems for this group. Given our likely problems with drug funding here, it was very useful to hear that in England they are successfully appealing refusals to fund the drug. They are using a combination of clinical information and human rights issues to argue the cases directly to their health funding authorities and are winning them all it seems. They are ready to go to court and all the HFAs have conceded, either after representations from the MPS society, or just before it gets to court. They have agreed to send me anonymous appeal samples for our information. Given the strong similarities between UK and NZ legal and health systems, this could be a big bonus for us in our inevitable dealings with Pharmac and government over these issues
5. Newborn screening received some good discussion and covered two main themes – First, to ensure early identification so therapy can be applied where some treatment or intervention is available (the standard approach to NBS I would say, once a reliable test is available); Second, the use of NBS to identify affected babies even if no treatment is available, but where the interventions made possible would (1) avoid the stress of delayed diagnosis, (2) alert families to the condition for optimal care, (3) warning of risk in future pregnancies. Most of the scientific presentations were focused on NBS as possibly leading to early therapy. The second aspect was there mainly through my pushing and questions, and I was able to get this discussed at the final wrap-up session. The theme I pursued was talking about a strategic approach to reducing the total incidence as well as the severity of impact on affected patients and their families, and how NBS might help achieve this when the technology is refined. There were no conclusions drawn about it, but it was well covered in session, as well as in private discussions with some key people (Ed Kolodny, Peter Meikle). It will need a lot more discussion, but it was noted by many key people there as an important issue needing more work on the science as well as ethics and screening policy. GOLD will have it in its agenda.

Some comments on the science presentations, as gleaned by me from the final reporting back sessions:

1. New approaches are being devised to avoid man-6 receptor difficulties and show some promise in improving targeting.
2. Direct injection of enzyme with AAV vector, and intrathecal injection to cross the blood brain barrier, are showing early promise in animal models. The intrathecal injection in an MPS6 dog, looked very interesting because of relatively simple tolerisation to avoid immune response and successful crossing of the BBB, with a remarkable benefit shown in a video of the treated dog. This seemed as dramatic as the benefit of direct injection gene therapy on CNS function in an Alpha- Mannosidosis cat, that I saw a video of in Washington.
3. Targetted synthetic drugs are also demonstrating a reduction of GAG synthesis.
4. Small molecule therapies are shown to cross the BBB.
5. Discussion on transgenics as a technically and financially promising way of producing enzymes for the future.
6. We can expect rapid progress in coming years for a number of Lysosomal diseases.
7. But in spite of this progress the unanswered questions seem to grow:
   1. Early treatment is important but what is the optimal time to start?
   2. How to deal with immune response?
   3. How to deliver enzyme to CNS, bone, joints and other problem areas?
   4. Can gene therapy provide persistent expression?
   5. Combination therapies might give best outcomes, but cost is a major issue in all countries.
8. Developments of therapy highlight need for good studies of distribution and impacts of these diseases in  whole populations, as well within patient groups.
9. Natural history data is needed.
10. International registries are needed and GOLD might play an important role in this, especially for the “super-orphan” diseases.

Overall, a very useful conference with a number of good outcomes. I greatly appreciate LDNZ’s support with registration costs for this meeting. Regards, John