Recombinant Technologies LLC — Department of Health and Human Services SBIR Phase I: N

Description

Abstract Alzheimer s disease AD is the most common cause of dementia among elderly patients afflicted by neurodegenerative diseases affecting about million people worldwide and regarded as the fourth most common cause of death Significant accumulation in the brain of Amyloid A is consistently observed in AD Due to its accumulation in AD removal of the toxic A from the system is expected to benefit AD patients Extensive efforts were devoted to developing therapeutic interventions targeting A and its clearance to treat AD but with limited success Ongoing modified attempts to target A using anti A antibodies or small molecule inhibitors of A production are yielding somewhat favorable success Although anti A antibodies meet the desired goal unintended immunological side effects in patients has been a concern We have developed and characterized a non immune based retro inverso peptide Amytrap with significant A binding properties We have shown that Amytrap can bind both soluble and less soluble forms of A A and A in vitro and that it can reduce A plaque size and A protein levels in the brain of a clinically relevant mouse model of AD and restore memory functions We have also shown that immobilized Amytrap peptide can bind and trap spiked A from sera samples in a concentration dependent manner Amytrap peptide is stable due to its D amino acid configuration and it is safe as it did not show any immune side effects in the AD mice In this phase we propose to develop an ex vivo system that could selectively remove A from the circulation without being systemically introduced into the patients We plan to generate and test a prototype extracorporeal column named Amytrapper to bind and remove A from plasma Currently there are no extracorporeal systems to treat AD patients Amytrapper is first of its kind to treat AD Amytrapper will be in the form of a cartridge containing a solid support chemically linked to Amytrap peptide We envision Amytrapper to be a part of a standard apheresis system wherein plasma from AD patients is passed through to selectively sequester A and A free plasma re enters the body Reducing the circulatory A will shift the amyloid equilibrium towards the periphery and thus will deplete brain A burden In this proof of concept study we will develop and characterize Amyrapper and test its performance with plasma spiked with A We will in Aim synthesize and characterize Amytrapper for A binding efficiency in Aim evaluate sensitivity and specificity of Amytrapper suspension format to bind A in plasma and in Aim prepare and test Amytrapper prototype column format for its sequestering ability of A in plasma We are confident to succeed in this effort as we have designed an appropriate target product plan with defined goals and deliverables Besides we have lined up the right industry leaders who are currently marketing FDA approved apheresis columns for other indications as CRO s to collaborate with us In subsequent phase of the study the device will be tested in a clinically relevant mouse model of AD followed by a first in human study Narrative Significant accumulation in the brain of Amyloid A is consistently observed in Alzheimerandapos s Disease We have developed and characterized a non immune based peptide Amytrap with significant A binding properties In this phase we propose to develop a prototype extracorporeal column called `Amytrapperandapos that could selectively remove A from the circulation Amytrapper will be in the form of a cartridge containing a solid support chemically linked to Amytrap peptide We envision Amytrapper to be a part of a standard apheresis system wherein plasma from AD patients is passed through to selectively sequester A and A free plasma re enters the body In this proof of concept study we will develop characterize and evaluate Amyrapper for its Amyloid binding performance We are confident to succeed in this effort as we have lined up the right industry leader to collaborate with us and we have designed an appropriate target product plan with defined goals and deliverables