Periodic Reporting for period 1 - REGENERA (COMMERCIALISATION OF A NOVEL PROTEIN VARIANT WITH NEURORESTORATIVE EFFECTS FOR AMYOTROPHIC LATERAL SCLEROSIS)
Okres sprawozdawczy: 2022-07-01 do 2023-12-31
I have discovered that MANF fragment is transported to the Brain, so it can be subcutaneously administered, is safe, economical, and has neurorestorative effects. In addition, my group has already demonstrated that MANF fragment has protective and restorative effects on motoneurons:
A clear improvement in motor coordination and a 2-week increase in survival and a protection of spinal cord motoneurons was observed after 4-week chronic subcutaneous MANF fragment administration in SOD1-G93A ALS mice.
Importantly, no off-target effects or in vivo side-effects were identified. Moreover, the selectivity of MANF fragment has the potential to be easily tailored to target indications beyond ALS to a myriad of neurodegenerative diseases with common mechanisms
In this project the effects of MANF fragment were validated in cell and animal models of ALS and we also performed an IP landscape analysis and establish freedom-to-operate (FTO) and analyzed the market structure. We additionally familiarized ourselves to competitive strategies that are being developed for the treatment of ALS
We were able to show that MANF fragment increased survival and motoneuron numbers in SOD1-G93A mouse model of ALS, MANF fragment also showed a tendency for neuroprotection in genetic TDP-43 rat model of ALS. We were able to witness a clear effect to inflammation : MANF fragment reduced the glial and astrocytic activation (as measured by IBA1 and GFAP analyses). In addition, MANF fragment had a robust effect and reduced ER stress and cell death in animal and in cell model. In addition we were able to detect a tendency for reduced neurofilament levels (After MANF fragment treatment in SOD1 animal). Neurofilament is a biomarker for ALS, increased levels of neurifilament levels tell about neurodegeneration and reduced neurofilament levels correlate with improved clinial score and neuroiprotection. .