Scientific materials that we currently use:
iPSC cell line with BAG3 P209L mutation (heterozygous)
isogenic iPSC cell line without mutation, i.e. a healthy cell line
isogenic iPSC cell line with BAG3 P209L mutation on both alleles (homozygous)
fibroblasts with the BAG3 P209L mutation
breeding mice expressing the human mutant hBAG3 P209L protein (the mice also have their own BAG3 protein)
[in progress] new mouse model in which mouse BAG3 will be replaced with human wild-type and mutant BAG3
In our research, we use a number of scientific studies listed on the BAG3 P209L mutation page.
Treatment strategies
drug repurposing - G, M and others [in progress, Poland]
editing of the mutated gene - Prime Editor [in progress, Germany, Canada]
silencing of the mutated gene - ASO [in progress, USA]
silencing of the mutated gene - siRNA [in progress, Germany]
silencing of the mutated and delivery - siRNA+cDNA in AAV [planned]
Current activities
[2024, October]
Participation in the WMS 2024 conference, establishing contacts with companies working on delivering BAG3 and companies delivering ASO to muscles
Bioinformatic analysis of the mutated BAG3 allele for the creation of ASO
Further experiments in mice using new targets (including M, G+B)
[2024, August]
Conducting nanopore sequencing to fully distinguish BAG3 gene alleles
Results of experiments on mice fed a G+B+S mixture
Establishing cooperation with a company searching for alleloselective ASO
Designing and preliminary tests of Prime Editor in Canada
Developing a protocol for observing the disease on cardiomyocytes in Germany
[2024, June]
Planning to create a new mouse model that will have the human BAG3 gene inserted in place of the mouse one (cDNA only)
[2024, May]
Participation in the Myology 2024 conference
Establishing contact with scientists from Canada working on Prime Editor
Establishing contact with a scientific unit from Hong Kong
[2024, February]
Extension of cooperation with the University of Gdańsk
First results of experiments on fibroblasts and G, B, S, M mixtures
[2023, July]
Signing an annex to the contract with the University of Gdańsk, allowing to hire an additional person to work
Planning further experiments
Presentation of the results of experiments on hBAG3 P209L mice
[2023, April]
First results of experiments on fibroblasts
[2023, March]
Delivering the mice to Gdańsk and starting their reproduction
In Germany:
testing the effectiveness of all siRNA variants for the BAG3 P209L mutation
creating and testing many Base Editor variants for mutation correction
further work on organoids created from iPSC-CM and attempts to induce disease symptoms
[2023, January]
Signing a research grant agreement with the University of Gdańsk
Delivery of fibroblasts to Gdańsk and start of experiments
Creation of the iPSC BAG3 P209L cell line from Krzyś's blood collected in June 2022
Creation of an isogenic iPSC cell line devoid of the BAG3 P209L mutation
[2022, December]
Establishing the rules of cooperation with the University of Gdańsk
Start of multiplication of mice (hBAG3 P209L) in Germany
Taking a section of Krzyś's skin for fibroblast culture at the Medical University of Warsaw
[2022, September]
In Germany, a lot of research is carried out at the University of Bonn on various cellular mechanisms initiated by cellular stress. One of them concerns exactly "our" mutation. The study in the first phase developed an animal model of the disease (currently the best in the world illustrating human disease). In the second phase, the project has the following objectives:
creation of iPSC-CM BAG3 P209L, i.e. cardiomyocytes grown from stem cells of sick children [it has already been done!]
preparation of a procedure for testing drugs or other compounds on the above cells [in progress]
screening of available drugs using the above procedure
development and testing of very advanced genetic tools for correcting mutated DNA on iPSC-CM cells
[Ongoing activities]
At the same time, we are conducting discussions:
with scientists from Poland, aimed at conducting drug tests on mice and/or on skin cells, i.e. fibroblasts
with scientists from the USA, with the participation of the Alexander's Way Foundation, aiming at creating a genetic drug
with scientists from the USA, with the participation of the Alexander's Way Foundation, aiming at discovering other methods of treatment
In our activities, we try to simultaneously support Polish science, which is why we are looking for scientists willing to cooperate.