The 12th International Symposium of Mucopolysaccharidoses and Related Diseases took place between June 28th and July 1st 2012 in the Netherlands. By: Raquel Marques of Portugal
The conference was intense and productive. We used our free time to have private meetings and informal conversations with some researchers: Graciana Diez-Roux/Andrea Ballabio (Italy), John Hopwood / Kim Hemsley (Astralia), Gregourz Wegryzn (Poland), Brian Bigger (UK), Alexey Pshezhetsky (Canada), Jerome Ausseil (France) and make an update on research.
To the researchers was also very important to meet us as well as our children. They feel how important are they to us. They stop seeing cell lines only, and start to see people too. John Hopwood, during our private meeting, finally got his own camera and took a picture of our group of Sanfilippo parents!
We devoured information. Our heads were spinning! Strong emotions, as always. I laughed and cried!
Seeing all the families around us , with some severe affected children, always give me a bitter / sweet feeling. Beautiful love stories , that sometimes carry me to an unknown future…
For MPSIII, was very encouraging to see how science is changing and how many progresses were made in genetic disorders. In the last couple of years, three types of treatments for MPS disorders were arisen and so many others are close. Seeing so many routes on research for MPS III and so many people around the subject, made me motivated. To go on!
Here are a few of my notes, most related to Sanfilippo:
- Brian Bigger
Everything is ready for a clinical trial with pure synthetic genistein in Manchester, UK. If they could get funded now, they could start tomorrow. The problem is that there are still 580.000 pounds missing and it is becoming really difficult to get this funding. As parents, we promoted several approaches amongst the Polish, the British and the Dutch to try to get an understanding and collaboration and finding a solution for the funding that is missing.
The principal investigator of the trial will be Simon Jones (Manchester).
B. Bigger also explained his project on pre-clinical studies of lentiviral haematopoietic stem cells transplant in MPSIIIA mice and the success on the results. Before proceeding to clinical trial, further studies are needed regarding toxicity. Brian Bigger will test the same therapeutic approach for type B.
- Alexey Pshezhetsky/ Brian Bigger – gene therapy (type C)
A new post doc was hired to work on the project, starting next September in Manchester. The rats were characterized in Canada, are considered good models and traveled to the United Kingdom.
At the moment, the type C colony C is prepared in Manchester. They already have the vectors that are going to be used. Within six months (starting from September), so by March, the plan is to inject the mice with the gene. Fingers crossed it will work!
Moreover Alexey Pshezhetsky has shown in its presentation that type C is slower to progress, compared to A and B, due to less accumulation of heparan sulfate.
- Graciana Diez-Roux / Andrea Ballabio
As in Geneva, Graciana came and spoke with our group, this time with Andrea Ballabio.
Ballabio explained the work that is being developed with the TFEB. He found that there is a 'master' gene that controls all functions of the lysosome, once it’s activated, promotes cellular clearance. This has been demonstrated both in vitro and in vivo, in animal models of various lysosomal diseases, including MPS IIIA mice.
He said this approach is a very promising therapy, but still in early stages, because they have to figure out the next phase, where does the eliminated material goes? To the bloodstream, urine? They have to find out ...
Moreover, in TIGEM’s lab, they were sponsored by BioMarin that bought a huge 'screening' machine, to find molecules that can activate the TFEB. At this time, they have screened 1500 molecules and had 150 hits. This is the first step, because from this 150, some can be used and some cannot. For example, if a molecule enables TFEB, but if kills cells around, it doesn’t fit. So the hits that they’re getting, are being subjected to various tests: activation, toxicity, etc ...
Ballabio used to work as a pediatrician, is a very sensitive person and passionated with his job. He chose investigating LSD’s because he wanted to help somehow families with affected children, that he was following as a doctor, some years ago.
- John Hopwood / Kim Hemsley –Australia group
They were very kind and made us an update on the project that TeamSanfilippo / StopSanfilippo started funding in February. They are studying pathology in Sanfilippo, what happens in the brain, can damage be reversible, what is the percentage on the production of new cells, are new cells healthy, etc ...
The project is moving fast. They concluded cells staining and are now studying cells movements. Marioko (the Phd student) took pictures of each stage of the project, showing all the specialized equipment used to cut parts of the brain slices (like salami), how it is weighted, etc..
Tracking cells will allow to know: how many cells are produced, what path they take, how they divide, if the new generation of cells are healthy, what kind of cells are created....
Now that they have stained cells, will try to get answers to all questions. The stained cells are growing in cultures. Let's wait...
- L. Calogera Simonaro – Monte Sinai school Medicine USA
With her presentation "Activation of the TLR4 pathway in the MPS: potentials for therapy"
Dr Simonaro demonstrated that the use of a molecule that is both FDA and EMA approved, polysulfat pentosan (PPS), had excellent results in MPS VI rats (bones and muscles) - the before and after videos had huge differences! PPS reduces the inflammation in the cells, reducing the severity of physical symptoms. MPS VI does not have neurological involvement like MPSIII.
We spoke with her, and she told us she was open to test the compound in MPS III mice, to see if the PPS can cross the BBB.
- F. Wijburg, G. Ruijter – AMC Amsterdam
His presentation 'Heparan sulfate in plasma and GAGs in urine correlate with disease severity in Sanfilippo disease', proved that there is a correlation between the plasma gags level and severity of the disease.
Lower HS levels in plasma and urine - more attenuated - less severe
On the posters section, one of them had the first results of Barbara Burton’s study 'High Dose Synthetic Genistein Treatment in MPS Patients with Neurological Involvement' . They used pure synthetic genistein at high doses (150 mg / kg / day ) in MPS II and MPS III patients. No side effects were observed and the product was well tolerated.
On another note, there was also Wegrzyn’s poster with his discovery that genistein enhances expression of TFEB, a regulator of lysossomal biogenesis.
-Regarding Lysogene’s gene therapy clinical trial, taking place in France for MPS IIIA, there was no presentation. Although, all four patients have been enrolled. However regarding the efficacy ,results will come out next year.
Below is a very useful link, were some videos and presentations from the conference are available:
Thanks to all of you, whom have supported our cause, science goes forward. Thanks to your help and contributions, every day researchers make progresses. THANK YOU!- Raquel
Raquel... I would be at a complete loss without her. Over the course of two years I have gotten to know her very well. We skype at least once a week. We have met each other in 7 different countries, stayed in each others homes and shared hotel rooms. Giggled like old school mates and cried like desperate Mom's.
Raquel is Portuguese she speaks perfect English; her French and Spanish is getting there. She's a beautiful soul and I'm so very thankful to have her in my boat. Raquel has 2 daughters, Joana is 8 now and her little sister Sophia will be celebrating her 4th Birthday on the same day as Jonah (July 30th.) How time flies. For Jonah and Joana the clock is ticking. Joana was born on leap year, so she's really only 2. :) So we like to tell ourselves. -Jill p.s. I don't know why the white box is there, it is a glitch.