EHE Research Updates
Dr Brian Rubin, who heads a small EHE research team at the Cleveland Clinic in the USA, is seeing exciting progress in a number of key areas. Several different streams within his overall research program are coming to fruition, with key results likely in 2018. Here is just a brief summary.
Therapeutic drug screening:
Dr Che in Dr Rubin’s team has been working to develop a drug screening assay to test a large number of potentially therapeutic compounds to see if they have any impact on the WWTR1(TAZ)-CAMTA1 fusion protein that is believed to be a key driver of EHE. The assay is now complete and Dr Rubin hopes to be testing compounds throughout February. The original plan was to test 50,000 but Dr Rubin hopes that this number may become even greater. If any of these compounds are shown to bind to the fusion protein, which is a key driving force of EHE, then greater analysis of the compound and the impact it may have will follow with a view to hopefully developing a therapeutic drug that can help us start to manage EHE. So Q1 will be an important period in the compound-screening schedule! This project also has a special place for our group as Dr Che is the post-doc that Dr Rubin was able to recruit with the funds we provided in 2016.
EHE mouse model:
At the current time there is no mouse model that we are aware of that is available for EHE research. Over the past 2 years Dr Rubin has been painstakingly working with other specialists to produce a genetically modified mouse model that has EHE. This has been done by genetically modifying the mice so that they have the key WWTR1(TAZ)-CAMTA1 EHE gene mutation and will produce the fusion gene that is believed to drive EHE. Earlier in the year Dr Rubin’s team had managed to achieve germline transmission of the gene mutation in the mice (the transfer of the gene mutation from the parents to their young during reproduction). These mice have been bred and allowed to grow, and in January 2018 Dr Rubin’s team will sacrifice some of the mice for the first time to see if they have in fact developed EHE tumors. If they have, we may finally have an EHE mouse model that can be bread and shared with other researchers interested in working to understand the disease. This would of course be a huge step forward.
Mekinist drug trial:
2017 saw the launch of the Mekinist (Trametinib) clinical trial for EHE patients with progressing EHE. This is the multi-institutional-trial that Dr Rubin had alerted the group to earlier in the year. The trial is led by Dr Schuetze from University of Michigan who is the Principal Investigator. This trial is designed based on Dr Rubin's preclinical research on EHE biology. Dr Rubin was delighted to have had 10 patients enroll by year-end, and believes that others are in the ‘pipeline’. This is important as this is sufficient to complete the first arm of the trial. It also demonstrates that the EHE community can be contacted and mobilized in sufficient numbers to make EHE research viable, something that had been openly questioned when Dr Rubin was proposing this trial. We are also supporting this trial financially as our EHE group have provided funding for the biopsies that Dr Rubin hopes people will agree to so that the real impact of Mekinist on EHE cells can be understood.
As part of the EHE Foundations patient support role, the group has also established a confidential closed Facebook page for patients taking part in the study so that they may be able to assist each other as they continue through the trial. We wish them all success as they participate in this important trial.