Platform Technologies
ICAM-1 Targeting Technology
ICAM-1 targeting may dramatically improve the efficacy of enzyme replacement therapy for lysosomal disorders.
Our approach is to target the CNS and peripheral delivery of the optimal enzyme through the ICAM-1 receptor. ICAM-1 is overexpressed in all tissues during pathological states, including NPD and other LSDs, making ICAM-1 an ideal, self-regulated target. The ICAM pathway, in which the cellular receptor ICAM-1 delivers molecules to lysosomes via clathrin and caveolae-independent mechanisms, is an elegant means whereby therapeutic ASM combined with the ICAM-binding peptide, as a fusion protein prodrug, can be delivered to the brain, thereby extending the ERT treatment to neurological NPD-A and AB patients.
In addition, since it is known that recombinant ASM reaches the lungs less efficiently than other systemic organs (e.g., liver and spleen), an ICAM-1-ASM prodrug could also be more effective for the pulmonary complications of NPD and allow for lower dosing to avoid toxicities. By improving targeting to the lungs, and potentially enhancing the circulation half-life and biodistribution to the major organs using glycan optimization, the ICAM-1 technology may lead to a safer and less costly therapy.
More broadly, this novel ICAM-1 fusion protein approach will be applicable as a platform for all existing LSDs, to enhance the transduction efficiency of ERT to the brain and other visceral organs. Once transduction efficiency to the brain is established for our ICAM-1-ASM fusion protein via validated biomarkers of CNS activity, our plan is to initiate development of the next ICAM-1/geCHO ERT program.
ICAM-1-Targeting-Technology
ICAM-1/geCHO: A Broad Platform to Address CNS Manifestation for Lysosomal Storage Disorders
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