2015 Events

Review of the Gene Therapy for GM2 Gangliosidosis Scientific Meeting 2015

On the 14th May The Cure & Action for Tay-Sachs (CATS) Foundation hosted the first ever scientific meeting for Gene Therapy for GM2 Gangliosidosis in Europe. Bringing together a variety of people; ranging from specialists in the field of gene therapy; health professionals who support individuals affected by GM2 Gangliosidosis (Tay-Sachs and Sandhoff disease); patient organisations; academics; and families with children affected by the diseases, the meeting discussed the development of gene therapy and the current work in this field.

Chairing the meeting was Dr Ivor Lewis who is an Honorary Consultant Paediatrician at East Surrey Hospital in Redhill. Dr Lewis gave a short briefing about what we wanted to achieve from the meeting and gave introductions to all of the speakers.


Talk 1 – Gene Therapy in the UK

The first speaker at the Gene Therapy for GM2 Gangliosidosis Scientific Meeting was Dr Claire Booth who is an Honorary Consultant in Paediatric Immunology at Great Ormond Street Hospital. Dr Booth’s talk gave a very interesting overview on how gene therapy has evolved over time and used the success of a treatment for Severe Combined Immunodeficiency (SCID) as an example of how an effective trial can be undertaken. Using treatment centres around the world, it was shown that Gene therapy for SCID works by correcting the genetic mutation in the hematopoietic stem cells (required for all immune cells) of the affected individual. Cells are removed from the patient’s bone marrow and, using special viral material, scientists introduce a functioning copy of the faulty gene that causes SCID. The corrected cells are then re-transplanted into the patient, and can use this functioning copy of the gene as a blueprint for making working immune system cells.

Dr Booth proceeded to describe the complex process of establishing a clinical trial and highlighted the variety of national bodies involved in approving the various stages of this process. Although this can be a lengthy process (it can take 10 years from the initial research idea to starting a trial) they all play important roles in ensuring the efficacy of the work and that all ethical considerations are discussed for a trial to start.


Talk 2 – Substrate Reduction Therapy Approach for Late-Onset GM2 Gangliosidosis

The second talk of the day was given by Gerry Cox who is Vice President of Rare Diseases Clinical Development at Genzyme Corporation. The basis of the talk was to introduce everyone to substrate reduction therapy and how this process works.

During the talk it was highlighted that symptoms of Tay-Sachs only begin occurring when someone has a HEX A enzyme activity level of under around 10%. It has been shown that people do not actually have to have large quantities of this enzyme to live a normal, symptom free life.

The talk continued to look at the discovery and development of substrate reduction therapy by explaining that in a metabolic or genetic pathway, enzymes catalyze a series of reactions. Each enzyme is regulated or mediated by one gene and at each phase in the pathway, enzyme activity catalyzes a reaction in which a precursor molecule (the substrate) is transformed into its next intermediate state. Failure of the metabolic pathway leads to accumulation of the substrate, with possible harmful effects. Substrate reduction therapy addresses this failure by reducing the level of the substrate to a point where residual degradative activity is sufficient to prevent substrate accumulation.

In the example of Late-Onset Tay-Sachs (LOTS), the disease occurs when harmful quantities of a fatty acid derivative called a ganglioside accumulate in the nerve cells of the brain. Gangliosides are lipids, components of cellular membranes, and the ganglioside GM2, implicated in LOTS is especially common in the nervous tissue of the brain. By manipulating the brain’s metabolism of GM2 gangliosides, an effective therapy could potentially be developed. An experiment described by Gerry Cox has demonstrated that, by using the enzyme sialidase, the genetic defect can be effectively bypassed and GM2 gangliosides can be metabolized so that they become almost inconsequential. This treatment could be developed further which would lead to causing the increased expression of lysosomal sialidase in neurons, which in theory could be an effective treatment for LOTS.

This innovative and ground breaking work is still in its infancy, but there is great excitement that a relatively non-invasive treatment for LOTS and other diseases may be on the horizon.


Talk 3 – Current works towards a gene therapy trial for GM2 Gangliosidosis in Europe

After a short break the third talk of the meeting was given by Dr Begoña Cachón who is senior member of the research team working with Professor Timothy Cox in the Department of Medicine at the University of Cambridge.

The talk began with an overview of the gene therapy project by Dr Cachón, a Senior Research Scientist at Cambridge based at Addenbrooke’s Hospital. She had developed this research over a 15-year period with Prof Cox and it includes spectacular results of the successful use of gene therapy in animal models of Tay-Sachs and Sandhoff diseases.

It was found that when mice that were an authentic model of these disease were given a single treatment in early adult life there was a greatly increased life quality and survival. In addition, it was found that the treatment prevented the onset of the devastating neurological disease that mimics the acute illness occurring in babies and young children. Further work in the laboratory has perfected this approach: given at the right time, long-term cures or near-cures are the rule.

In October 2013 the team received a £2.84 million grant from the UK Medical Research Council to develop and fund the clinical trial for a treatment for Tay-Sachs and Sandhoff diseases. Already several planning meetings have taken place and more will be needed with a variety of regulatory bodies as required to approve all the work so that the trial can start.

Prof Cox gave a update on how this large project has been progressing and outlined enrolment and other criteria for the trial. One of the main milestones involves developing the best clinical vectors for delivering the corrective genes safely and effectively in the brains of the patients with the disease.

Reporting on how the work has been progressing, he outlined one of the main milestones, which involves the selection of the exact type of vectors for delivering the therapy and which would be approvable for human use. However, when used in one of the animal models, vectors now being obtained from a facility in London did not have the desired effects and so unfortunately the project will need to be subject to a delay – estimated to be 6 or as much as 12 months – for this milestone to be achieved. The entire team and collaborators have examined the options in order to explain this unexpected effect and an action plan was in place to re-establish progress as quickly as possible. Although this was disappointing news, there is every hope that the problem can be rectified – beyond a delay in the start of the trial of up to 12 months.

With the expected support of the Medical Research Council, the research team should be able to continue with its work to make this trial of gene therapy a reality and one that could enter the phase of more prolonged testing across the board (phase 3 studies). Clearly the CATS Foundation would be kept regularly informed of progress.


Talk 4 – Overview of a patient organisation involvement in the gene therapy trial for GM2 Gangliosidosis

The last talk of the meeting was by Daniel Lewi, one of the founders and the Chief Executive of The Cure & Action for Tay-Sachs (CATS) Foundation. This talk focused on the role the charity has played since it was launched in 2011 in supporting families and the work towards a potential treatment.

The talk highlighted the fact that the charity plays an important part in the development of the trial as we represent the patient interests. The charity also asks the difficult questions about who will take part, explaining that a focus should be on the quality of an individuals life rather than quantity. The risks about taking part are also a subject the charity discusses extensively with the trial team as it is important for people to understand the possible outcome of taking part in the gene therapy trial.

During the talk our support of the research was also highlighted through our new initiatives. These include employing our Family Support Officer, Nikki Backus, who is now the direct liaison with all the families in the UK with a child affected by Tay-Sachs or Sandhoff disease. The role will be expanded once the trial begins to support those individuals selected to take part in the trial.

Another new initiative discussed in great depth was the launch of the European Registry for Tay-Sachs and Sandhoff disease. This database has been developed and created in collaboration with our Spanish charity partner Acción y Cura para Tay-Sachs (ACTAYS) and was funded by a €7,000 grant from the Stop Tay-Sachs Association. The registry will enable us to record in detail all those people affected by the diseases. It will also help us begin to build a deeper understanding of the prevalence of Tay-Sachs and Sandhoff disease in Europe, the onset of the different symptoms and the various different gene mutations of the diseases.


Summary of the Gene Therapy for GM2 Gangliosidosis Scientific Meeting

The meeting was a huge success and was very well attended. It was an amazing experience to bring together people form all over the world and there were attendees from Oxford University, Cambridge University, Addenbrookes Hospital, Evelina Children’s Hospital, Guys & St Thomas’s Hospital, East Surrey Hospital, Great Ormond Street Hospital, Manchester Children’s Hospital and Alder Hey Children’s Hospital. We also had doctors who travelled from Spain, Australia and America join us along with families from the UK, Germany and Spain.

If you would like more information about what was discussed during the meeting please get in touch with us.





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1 Comment

  1. connie
    September 7, 2015

    Hi, I am a mother of three year old little girl who was diagnosed with GM2 Gangliosidosis AB Variant in April of 2014. It’s been very frustrating trying to locate any information on the condition itself and or pending possible treatment in the works. Your website is the first I’ve seen that gave me a little bit of hope. I was wondering if in the near future, you guys will be coming to the US? For whatever reason, I can’t located any support group located in the US. Everything I’ve seen in the Internet is in the UK which is far from me. But I am grateful for your website and the great information that is provided.

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