Just a short note highlighting our trip to Geneva for Sanfilippo Congress. Sorry for any typos, I am blasting this out fast.
I have tried my best to relay the information as I received it. I am not a scientist nor am I a doctor. So, with that said, I ask that you take my interpretation with a grain of salt.
Of course, I want everything to be positive. I am a positive person! However, I have tried to share the good news and the bad news as I received it without filtering. In particular, I have already had parents reach out to me about Prof. Hopwood’s data showing a reduced efficacy of ERT in mice past a certain age. Regarding this data, I will share with you what I was told; Humans are not mice. There significant differences in anatomy in humans and mice; enough so that one cannot translate clinical outcomes of animal data to humans. The primary hypothesis that was proven via the mice data was that, indeed IT ERT does work in animals. What this data may suggest is that there is A point where IT ERT doesn’t work anymore. Understanding where the “point of no return” for humans is will require testing in humans, there is no way around that.
The temptation to extrapolate from mice data to humans is understood. It doesn’t only happen to laypeople; researchers do it too.
What I liked:
1) Meeting the researchers
2) Meeting the families:
3) Getting latest Info (Good and Bad), more details to follow
- Hopwood: Intrathecal ERT - In mice IT ERT doesn't seem to work if started after symptoms present clinically. However, HUMANS ARE NOT MICE, and we hope to see data from Shire's Phase I/II in 6 months, at the end of the Phase I/II . At that point they will have some efficacy data along with an idea of the correct dosing regimen. Fingers crossed!
- Genistein: Professor Wergzyn and Brian Bigger presented data on genistein. There is growing consensus that it has an effect in mice at high doses. There is interest in launching a double-blind placebo controlled trial for genistein within the next year.
- Important note: Dr. W showed that there was significant variability of genistin content in the "natural" version of these products. Further, he showed that there were some negative synergies involved with some of the other compounds used in those products. In other words, you may be better off using nothing than using the natural versions of this compound used in some supplements.
- As far as I know, the only way to obtain the pure synthetic version of genistein in the US is to either be part of Dr. Burton's study in Chicago or through Fallon Pharmacy.
- Natural History Study - Shire has identified several new biomarkers and learned much about the disease through the University of Minnesota study. These biomarkers are so important, not only to understand what works from a treatment pespective but also to get drugs approved. Accelerated approval relies on proper biomarkers as surrogate endpoints. Here are some of the key findings:
- Brain volume decreases along with time. Also, it was shown to correlate well with the cognitive decline, as measured by the ratio of cognitive age to chronological age.
- Brain volume can be computationally measured by analyzing MRI data.
- Cerebro-spinal Fluid GAG levels are fairly constant with time. In other words, the do not increase with disease progression
- Two new bio-chemical markers were found. I don't recall both of their names but one was called Hepatocyte Growth Factor.
- Inter cerebral Gene Therapy (France): At least one patient has been treated. No safety issues so far. Four French patients will be included. The trial will expand to a phase III in a couple of years based on data from the Phase I/II. A phase I/II study for Sanfilippo B patients will open by the end of next year. They are looking to include eight European patients younger than 6 years of age.
- Dr Fu's Gene Therapy: Dr. Fu is using a new gene therapy vector than the folks in France. Her vector can be administered intravenously - versus through direct injection to the brain. They are completing the animal toxicology work and hope to open a Phase I/II trial in three or so years.
- Prof. Doug Mccarty, Dr. Fu's colleague, also described a program for gene therapy for MPS IIIA. Like their type B program, it can be administered intravenously. It is several years behind the Type B program and lagging further behind from a funding perspective. On the positive side, they have learned much for their MPS IIIB gene therapy that has allowed them to produce a much more "efficient" vector for MPS IIIB. That means that the viral vector used can work with fewer vectors. This makes it more cost-effective and even safer.
I am very grateful for drug companies and the researchers who have taken up this fight along with families. I am also grateful for the families that have participated in the Natural History Study of these diseases. It is a tough choice for families to get involved. The procedures are invasive and the time commitment is a burden. However, the data is so valuable in the fight against these awful diseases.
Finally, we should all be very grateful for the contributions of Shire to our children. They have shown an amazing commitment to Sanfilippo. By their own financial statement one can assume that they have poured tens of millions into research. Further, their openness in sharing their natural history findings and biomarkers is a contribution to the community as a whole.