Summary
Stem cells led to effective cures for diseases of blood and epithelia. However, in the case of diseases affecting muscles, connective tissue or brain, significant challenges persist for expansion of a sufficient number of corrected cells, delivery and engraftment. Even when these problems will be solved the prospective per-patient cost of the treatment (up to 2M$) will make such therapies unsustainable for NHS. We developed protocols of cell therapy using mesoangioblasts (Mabs), vessel associated progenitors that, despite promising results in animal models, showed modest efficacy in patients. To address this, we transplanted autologous dystrophic Mabs expressing a small nuclear RNA engineered to skip dystrophin exon 51, that enters and corrects also neighboring nuclei of the multinucleated muscle fiber, thus bringing dystrophic production to therapeutic levels. A Phase I/IIa trial is currently running. Even in case of success, the cost would remain prohibitive.
Through the ongoing ERC ADG 884952-UniMab, we are completing the development of immortal, immune-privileged Mabs from dystrophic patients thanks to genome editing of HLA and the expression of tolerogenic proteins. In this PoC project we will produce universal Mabs from healthy donors and will study the feasibility of producing and storing a large amount of universal Mabs through a bank of universal donor Mabs from healthy patients, ready to be corrected for the specific genetic mutation and injected into the patient following the motto “one serve many”. Available cells, a GMP-grade lentivector, expressing the wt cDNA of the mutated gene and a mouse model for pre-clinical tests would be sufficient to start a trial even for extremely rare diseases that currently lack even the hope of a therapy. This work will enable the business exploitation of the MABANK technology, by creating a company with a GMP biobank that may operate internally and make cells available to clinicians and Biotech companies.
Through the ongoing ERC ADG 884952-UniMab, we are completing the development of immortal, immune-privileged Mabs from dystrophic patients thanks to genome editing of HLA and the expression of tolerogenic proteins. In this PoC project we will produce universal Mabs from healthy donors and will study the feasibility of producing and storing a large amount of universal Mabs through a bank of universal donor Mabs from healthy patients, ready to be corrected for the specific genetic mutation and injected into the patient following the motto “one serve many”. Available cells, a GMP-grade lentivector, expressing the wt cDNA of the mutated gene and a mouse model for pre-clinical tests would be sufficient to start a trial even for extremely rare diseases that currently lack even the hope of a therapy. This work will enable the business exploitation of the MABANK technology, by creating a company with a GMP biobank that may operate internally and make cells available to clinicians and Biotech companies.
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More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101137970 |
| Start date: | 01-09-2023 |
| End date: | 28-02-2025 |
| Total budget - Public funding: | - 150 000,00 Euro |
Cordis data
Original description
Stem cells led to effective cures for diseases of blood and epithelia. However, in the case of diseases affecting muscles, connective tissue or brain, significant challenges persist for expansion of a sufficient number of corrected cells, delivery and engraftment. Even when these problems will be solved the prospective per-patient cost of the treatment (up to 2M$) will make such therapies unsustainable for NHS. We developed protocols of cell therapy using mesoangioblasts (Mabs), vessel associated progenitors that, despite promising results in animal models, showed modest efficacy in patients. To address this, we transplanted autologous dystrophic Mabs expressing a small nuclear RNA engineered to skip dystrophin exon 51, that enters and corrects also neighboring nuclei of the multinucleated muscle fiber, thus bringing dystrophic production to therapeutic levels. A Phase I/IIa trial is currently running. Even in case of success, the cost would remain prohibitive.Through the ongoing ERC ADG 884952-UniMab, we are completing the development of immortal, immune-privileged Mabs from dystrophic patients thanks to genome editing of HLA and the expression of tolerogenic proteins. In this PoC project we will produce universal Mabs from healthy donors and will study the feasibility of producing and storing a large amount of universal Mabs through a bank of universal donor Mabs from healthy patients, ready to be corrected for the specific genetic mutation and injected into the patient following the motto “one serve many”. Available cells, a GMP-grade lentivector, expressing the wt cDNA of the mutated gene and a mouse model for pre-clinical tests would be sufficient to start a trial even for extremely rare diseases that currently lack even the hope of a therapy. This work will enable the business exploitation of the MABANK technology, by creating a company with a GMP biobank that may operate internally and make cells available to clinicians and Biotech companies.
Status
SIGNEDCall topic
ERC-2023-POCUpdate Date
12-03-2024
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