UK & Ireland Fanconi Anaemia Family/Clinical Network

We are now on the countdown to raising our first £100,000, with only £6000 to go!

This amazing figure, achieved in less than two years, is due to the magnificent efforts of our FA families and friends across the UK and Ireland.

This has enabled us to publish the first UK Standards of Care, hold Clinician and Family meetings and provide over £30,000 for UK FA research. We will also shortly be funding an international gene therapy workshop and making a further significant donation to UK FA research.

Thank you everyone!

National Institutes of Health grant expands OHSU’s 15-year research effort into the cause, prevention, treatment of the disease.

Oregon Health & Science University is partnering with the University of Oregon and Harvard Medical School to expedite basic science research into new and existing drugs and compounds that may prevent the complications associated with Fanconi anemia, an inherited condition that can lead to bone marrow failure and cancer.

With a new $10.7 million grant from the National Heart Lung and Blood Institute, a branch of the NIH, the research teams will screen and sort thousands of drug candidates in mice at OHSU, zebra fish at UO and human cell lines at Harvard.  more

Many thanks are to due to Dr Helen Walden of Cancer Research UK for organising the first UK FA Research Conference, held on May 24th.

 A big thank you also to Cancer Research UK for funding the event. In supporting this event and in funding FA research, Cancer Research UK has shown its commitment to FA research as a means to furthering research into cancers in general.

The conference was attended by 25 researchers from the FA  molecular/cell biologist community and also a representative from the FA gene therapy community, Prof  Linda Lako, whose research Fanconi Hope is currently funding.

A representative from Fanconi Hope was kindly invited to attend and to speak briefly at the outset to explain the charity’s role in trying to bring together the UK FA research community and in expediting FA research.

It was very encouraging to see so many of the the researchers meeting for the first time and discussing ways of helping each other. It was also gratifying to realise that there were now in excess of 25 researchers from across the UK working in just this one area of FA research – molecular biology.  When you add the researchers working in other aspects of FA research it proves there is a significant body of research now in the UK devoted to Fanconi Anaemia.

One of the conclusions from the event was that there was an appetite for further such events. Fanconi Hope fully supports this and intends to be actively involved in the organisation of future research conferences not only in the molecular biology field but in FA research more generally.

The programme of events can be downloaded here.

Prof Lako discussing her Gene TherapyResearch	Prof Neil McDonald and Dr Helen Walden in discussion during the coffee break	Dr Ambrose Cole discusses the FA Core Complex	Question Time

Thomas Carroll and Bob Dalgleish of Fanconi Hope attended the British Society for Gene Therapy’s Annual Conference in London on March 29th. Thomas Carroll spoke at the invitation of the BSGT president, Professor Adrian Thrasher on the Public Engagement Day on  ”Fanconi…hope: from ‘Saviour Sibling’ to gene therapy”. Thomas attended for the whole duration of the 3 day conference and was able to meet with a large number of researchers in the gene therapy community to promote the concept of using FA as a target for their research. Fanconi Hope’s sponsorship of the event, entailed covering travel expenses for  Dr Juan Bueren, one of the world’s leading researchers of gene therapy in Fanconi Anaemia, who presented on his ground-breaking work. Fanconi Hope also paid for a ‘bag drop’ which allowed us to target the gene therapy research community with an information sheet to encourage them to consider using FA as the basis of their research.

Fanconi Hope has Trustee membership of the BSGT and is now an official charity sponsor.  Our logo can now be seen on their Charity partners web page. We recognise the tremendous significance of gene therapy as a potential cure for FA and are seeking to expedite the move from basic research to clinical trials through helping to link relevant groups and individuals and through lobbying for Eu funding to support trials.

Our Information Sheet for the Gene Therapy research community	Thomas Carroll presenting on “Fanconi…hope: from ‘Saviour Sibling’ to gene therapy”	Thomas (left) in discussion withProf Adrian Thrasher (2nd L), current BSGT president and Prof Len Seymour, past president.(on right)

Fanconi Hope is one of a number of groups sponsoring the British Society of Gene Therapy Annual Conference to be held in London, 29th -31st March. The event is chaired by Professor Adrian Thrasher, the BSGT President, who some of you may recall, gave a presentation at our last Family Meeting.

Thomas Carroll, our Chairman, will be giving a talk entitled “Fanconi…hope: from ‘Saviour Sibling’ to gene therapy” on Monday 31st March and Dr Juan Bueren, who also presented at our Family Meeting will be talking on Wed 31st March on “Gene Therapy and Cell Reprogramming Approaches in Fanconi Anemia”

Fanconi Hope, who have Trustee membership of the BSGT, are sponsoring Dr Bueren’s attendance expenses and paying for a ‘bag drop’ which allows us to disseminate targetted Fanconi Hope literature to all those involved in Gene Therapy. This material will seek to persuade them to consider using Fanconi Anaemia as a basis for Gene Therapy research and trials.

We are pleased to welcome our three latest Research Network Members, Prof Majlinda Lako, Peter McHugh and Dr Michael Carty:-

Prof Lako’s group at Newcastle University focuses their research on understanding of the basic biology of human embryonic stem cells, their self-renewal and differentiation to haematopoietic, retinal and corneal lineages.

Peter McHugh runs the DNA Damage and Repair Research Group at Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford Peter’s group has an increasing interest in FA, and has recently published their first paper in this area. Peter regularly participates in the US FARF, is giving a lecture this year, and is a regular grant reviewer for the FARF.

Michael Carty’s group at the DNA Damage Response laboratory at NUI, Galway have an interest in Fanconi Anaemia as part of their research into the responses of cells to DNA damaging agents such as cisplatin and mitomycin C, and to mitosene derivatives synthesized by colleagues in the School of Chemistry at NUI, Galway.

 Research just published in Nature Structural and Molecular Biology by Dr Helen Walden of Cancer Research UK (and a member of our UK FA Research Network) describes how her team have unravelled the structure of the FancL protein.
Dr Walden says “We have taken the first full atomic snapshot of a protein in this cell repair pathway, right at the very heart of the route by which cancer cells defend themselves against treatments which are intended to destroy them. By blocking this repair ‘ignition switch’, it may be possible to boost traditional treatments. As such, it’s a drug target.”

This link between FA and potential mainstream cancer cures amply illustrates the importance of spending money on research into orphan diseases such as FA. This is clearly recognised by Cancer Research UK as they have over 7 people  in 2 separate research labs currently working on FA. 

More: http://news.scotsman.com/science/New-hope-as-cancers39-.6071258.jp

The Ethics and Law Advisory Committee (ELAC) have now considered the outcomes of the consultation event and have made recommendations to the Authority for the future licensing of preimplantation tissue typing.  In summary,  ELAC have recommended that for preimplantation tissue typing a case-by-case approach should be maintained for the immediate future, that there should be a commitment to further a further reduction in the time taken to make decisions, and that a greater range of information should be made available on the HFEA website for people seeking this kind of treatment.
 
The Authority considered the recommendations of ELAC on 20th January and key decisions will be published on the HFEA website shortly.  
The ELAC papers and the minutes of the discussion had by the Committee can be found here:  http://www.hfea.gov.uk/5669.html
The Authority papers are now published , and can be found here: http://www.hfea.gov.uk/5721.html

Fanconi Hope is pleased to announce that in collaboration with the US Fanconi Anemia Research Fund we have provided a grant of £30,000 for the first UK research programme relating to the use of stem cell technology in conjunction with gene therapy which may in future provide a cure for Fanconi Anaemia; ‘Using iPSC technology to understand early haematopoietic development in Fanconi Anaemia patients’.  Fanconi Hope’s research grant of £30,000 is now funding the first phase of the work, and we have set ourselves a target of raising a further £100,000 for the remaining phases.

Background:

Recent joint research by the Salk Institute for Biological Studies in Calfornia, the Center of Regenerative Medicine in Barcelona (CMRB) and the CIEMAT Centre in Barcelona have shown for the first time that in principle human genetic diseases such as Fanconi Anaemia can be cured using a combination of gene therapy and induced pluripotent stem (iPS) cell technology. 
The potential significance of this is that corrected cells from the patient’s own tissue would be used in a bone marrow transplant thereby avoiding the issue of tissue rejection which often causes cancers subsequently in transplanted patients.
This groundbreaking research has been shown to cure an FA-affected cell and in theory this could then be transplanted into a FA-affected patient to cure the blood-related element of the disease. However many hurdles remain before the theory can become practice not least in preventing the reprogrammed cells from inducing tumours, and the international team are now funded to pursue research aimed at translating basic science into clinical cures. 

Prof Majlinda Lako

Prof Chris Mathew

Now for the first time in the UK a collaborative research programme into this exciting new technology has been initiated between a group in Newcastle led by Prof Majlinda Lako working with induced pluripotent stem (iPS) cell technology and a group in London led by Prof Chris Mathew researching in Fanconi Anaemia.

In brief, the programme involves generating and characterising iPS cell lines (the first phase of the programme). Next, the team will study whether these iPS cell lines behave the same way as normal FA cells with respect to DNA repair, genomic instability and the ability to make blood cells. If they do, they will then have a good FA model (which can be used in a laboratory environment rather than testing on humans) to test different corrective measures/drugs for the faulty DNA repair mechanism. The team will then investigate to see whether the process of creation of blood producing cells is different for FA and control patients. This should give a better understanding of what goes on so that hopefully they can help improve the process of curing patients through new therapeutic regimes using gene therapy and iPS cell technology.

This research project is being funded by Fanconi Hope in collaboration with the Fanconi Anemia Research Fund (FARF) in the US. Fanconi Hope has provided a grant of £30,000 for the first phase of the work and has set a target of raising a further £100,000 for the remaining phases. This research topic was selected by the Trustees of Fanconi Hope from a shortlist of candidate UK research programmes which have been approved for funding by the FARF Scientific Advisory Board, whose 14 members comprise FA specialists from the US, Canada, Holland and the UK.

Further details of the research can be found on the Fanconi Hope Funded Research page.

An HFEA Consultative Meeting was held on 1st Dec 2009 to review the licensing conditions for PGD for later onset, lower penetrance conditions and for HLA tissue typing. See Agenda and Discussion document – case by case approach to PGD

The meeting was attended by around 50 people with speakers for and against change. Attendees with an interest in FA included Dr Josu de la Fuente from St Mary’s Hospital, London, Colleen Lynch from Genesis Genetics and Bob Dalgleish from Fanconi Hope. This post is written by Bob Dalgleish.

An introduction from Juliet Tizzard, HFEA Head of Policy was followed by presentations from:-

- Dr Sue Price, HFEA Authority Member
- Dr Sioban Sengupta, UCL Centre for PGD
- Dr David King, Human Genetics Alert

Presentation material from the first two speakers is available on request. (Dr David King spoke without supporting material).

2 Consultation workshops were then run in parallel:-

Workshop A. Case-by-case licensing of lower penetrance, later onset conditions. (No Fanconi Hope representation)
A workshop in which participants were asked for their experience of the
case by case licensing process lower penetrance, later onset conditions
and consulted on alternative models for the future.
 
Workshop B. Case-by-case licensing of tissue typing applications. (Attended by Bob Dalgleish from Fanconi Hope)
A workshop in which participants were asked for their experience of the
case by case licensing process for preimplantation tissue typing and
consulted on alternative models for the future.

In Workshop B three options were presented for discussion, namely;

Option 1. Status quo: Continue to license applications on a case by case basis. The Licence Committee
would continue to be responsible for licensing novel conditions, and the ELP responsible for
licensing applications from subsequent families, on the basis of evidence provided from the
clinician responsible for the sibling’s care. This delegation of subsequent decisions to the ELP
may help to resolve concerns about the time the process takes.

Option 2. Centres to notify the HFEA of the intention to tissue type. The Licence Committee would
continue to licence novel conditions. Clinicians would assess the appropriateness of treatment in
particular family cases, using HFEA Code of Practice guidance. Centres would simply notify the
HFEA that they intended to tissue type, by supplying to the HFEA a letter indicating the support
of the sibling’s treating clinician.

Option 3. Cease consideration on a case by case basis. The Licence Committee would continue to license
novel conditions. The clinician would have responsibility for deciding the appropriateness of
treatment in particular cases, using HFEA Code of Practice guidance. The HFEA would require
clinics to obtain the support of the sibling’s treating clinician, as currently set out in the case by
case application form. Evidence of this support and adherence to Code of Practice Guidance
could be checked on inspection.
It was clear that few could see the logic or benefit of case-by-case applications as the application forms per family were ‘largely cut and paste’ according to the London PGD/HLA/IVF provider so the decision was not actually being made on a per family basis in any case. The HFEA were also unable to say whether for any two families with the same condition different decisions had been made.  It was seen that the patient’s clinician was in the best position to judge the appropriateness of PGD/HLA/IVF and those clinicians were already working within a framework of HFEA guidelines so the checks and balances were still there. This view came from across the spectrum of clinicians, both PGD/HLA/IVF providers and support groups.

Of the 3 options, out of around 18 participants I believe 17 voted for Option 3, with only Dr David King dissenting.
The forum was advised by the HFEA that taking position 3 required acceptance of the fact that the HFEA could review the position in the light of new evidence such as embryo damage during cell selection.

Plenary Session Summary
Danny Edwards summarised the Tissue Typing Applications Workshop View in the Plenary Session as follows.
There was a very strong view that HLA tissue typing should be brought into line with PGD, and in fact there is an even stronger justification for this than for cancer predisposition. This would mean a move away from case-by-case approval removing one of the main uncertainties for families, who already have to deal with the uncertainties of funding, in particular as some funding bodies will not consider funding until the HFEA have licensed the case of a particular family.
This will require a Framework of Guidance which will define for which conditions HLA will always be the best treatment.
There was a call for more research on cure rates as there is a lack of information for families on the efficacy of the treatment.

The summary on Licensing of Lower Penetrance, Later Onset Conditions was that this had to be considered on a condition by condition basis as to whether it should be agreed on a case-by-case basis

Next Steps
The recommendations will be taken to the Ethics and Law committee on 15th Dec with subsequent recommendations to the HFEA in January 2010.