Brain Shuttle - a brain selective drug delivery tool

Purpose and goal

Our aim is to develop a unique technology platform to improve or enable protein drug delivery into the brain - a major hurdle in todays´s drug development for brain disorders. Our solution is a unique product consisting of a carrier X + a chemical linker which can be chemically conjugated to the drug of choice (the ´cargo´). In this prestudy the key goal was to show increased brain uptake of at least one of two model proteins when conjugated to our compound. Two subgoals were achieved (MS1 & 2, see below) but not the key goal, proof of concept, due to that we got surprisingly low serum levels in vivo.

Results and expected effects

MS1: Prod. 3 diff carrier-linker compounds in total. Of the first two, one (BS2) was active on the target (at 6.6 uM). Not impressive but we decided good enough for testing the concept. Recently we made a new compound, BS3, with 4x better potency than BS2. MS2: Conjugation of BS2 to protein. Bigger challenge than expected but we solved it. However could not get enough concentration or level of conjugation ratio BS2/protein due to precipitation of the conjugate at higher conc or BS2/protein ratio. This limited the max dose in vivo but we still expected much higher serum levels than what we got.

Approach and implementation

Collaboration with KeyToLead for synthesis of our carrier-liner compounds worked out very well, despite challenges in the synthetic route for some of the compounds. Collaboration with experts at BMS, Uppsala Univ. to develop conjugation methodology for BS2 to our model proteins went very well too. Despite several unexpected problems that emerged during the process and delayed us up to 4.-5 months, it was solved thanks to the expertise at BMC. We now know we need better potency of the carrier-linker + higher conc of the conjugate to reach serum levels in vivo closer to the carrier EC50.