Neuroregenerative peptide treatment for multiple sclerosis

Project Information

REGENERA MS

Grant agreement ID: 101158120

DOI

10.3030/101158120

Project closed

EC signature date 12 February 2024

Start date 1 July 2024

End date 31 December 2025

Funded under

• European Research Council (ERC)

Total cost

No data

EU contribution

€ 150 000,00

Coordinated by

HELSINGIN YLIOPISTO
Finland

Periodic Reporting for period 1 - REGENERA MS (Neuroregenerative peptide treatment for multiple sclerosis)

Reporting period: 2024-07-01 to 2025-12-31

Summary of the context and overall objectives of the project

Multiple sclerosis (MS) is a chronic inflammatory, autoimmune, and neurological disease without a cure, affecting the lives of 1.2M Europeans and causing significant economic costs to patients and society. MS primarily affects young adults aged 20-30 and is characterized by demyelination and neuronal death, where the immune system mistakenly targets the protective myelin covering of nerve fibers. This results in neurological impairments such as tremors, stiffness, and bladder problems, significantly impacting patients’ daily lives, independence, mobility, and social interactions.

In the REGENERA MS project the technical and commercial potential of MANF fragment a groundbreaking therapy with neurorestorative potential for the treatment of multiple sclerosis (MS) was investigated
We validated the effect of MANF fragment in in vitro (Olineu cells, in vitro OPC cultures) and in vivo models of MS (EAE and LPC mouse models) and studied the IP strategy and business development including market research and engagement with industry.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

We were able to show that MANF fragment induced remyelination, improves motor coordintion and reduce symptoms in an animal model of MS. In more detailed,
we were able to show that C-MANF suppresses neuroinflammatory activation and facilitates the recovery of
oligodendrocytes after demyelination, while reducing long-term activation of the UPR. Furthermore, we showed that
C-MANF enhances myelination of primary OPCs in culture, that promotion of remyelination in cerebellar organotypic slice
cultures is dependent on UPR-modulation, and that exogenously applied C-MANF suppresses chronic activation of all
three UPR pathways in oligodendroglia. Finally, we showed that demyelination in MANF-deficient brains (analyzing MANF knock out mice)
leads to extensive neuroinflammation and CNS degeneration, implicating UPRmodulation by MANF as a key component in tissue responses
to demyelination. Altogether, we show that UPR modulation with C-MANF is a promising new therapeutic approach for
treating neuroinflammatory demyelination.

Regarding the business developent activities, during the REGENERA MS proect, we were able to file a new patent application, conduct a market study and make a thorough research on competitors in the MS market.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

As summary, C-terminal fragment of MANF (studied in the Regenera MS project)
significantly improved clinical recovery in EAE mice via improved remyelination and
suppression of neuroinflammation in the CNS. We also showed that
endogenous MANF is a key player in restoring tissue homeostasis
following demyelination. This is a result of a novel form of UPR
modulation, and presents a new therapeutic avenue for treating diseases featuring autoimmune demyelination, such as MS.
Based on these results we can say that MANF fragment has clear potential in the treatment of MS.
As there are no MS drugs that can induce remyelination, MANF fragment also has high commercial potential.