# Discovery of Novel Blood-Brain Barrier Targeting Antibodies for the Treatment of Alzheimer's Disease

> **NIH NIH R43** · ABILITA BIO, INC. · 2021 · $432,856

## Abstract

SUMMARY
Over 5 million Americans suffer from Alzheimer’s Disease (AD). The approved therapies available for AD only
treat symptoms and do not address the underlying neurodegeneration. Importantly, disease-modifying
therapeutics (DMT) to delay onset or progression of AD could reduce up to 50% of AD cases. However, the
major hurdle to developing DMTs for AD is the largely impermeable blood brain barrier (BBB). 98% of all
systemically administered therapeutics and virtually all antibodies fail to reach the brain, and thus are ineffective
at treating AD. Members of BBB transporters have been previously used to transport nanoparticle formulations,
but are associated with significant scientific complexity and toxicity risk. Abilita Bio will circumvent these risks by
using its proprietary and innovative platform, Enabled Membrane ProteinTM (EMP), to develop single domain
antibodies (sdAbs) that will latch onto transporters without altering their natural function, enter the BBB via
endocytosis, then into the brain via exocytosis. However, expression level of transporters and their efficiency
widely vary. Therefore, Abilita Bio will take a multi-target approach to identify a strong candidate. We have
identified transporters from 4 different functional subfamilies to test as novel antibody targets to deliver AD
therapeutics through the BBB.
The goal of this Phase I SBIR proposal is to develop sdAbs of our 4 identified targets and perform proof-of-
concept of BBB transport in vitro. This will be accomplished through the execution of 3 aims. In Aim 1, we will
use our EMP platform to evolve the 4 targets to generate variants with enhanced properties while maintaining
wildtype function. In Aim 2, we will immunize llamas with our EMP variants to develop sdAbs against each target.
We will test sdAb hits for specificity and affinity. With our two top hits, we will perform in vitro proof of concept
studies using a microfluidic-based BBB model. This model provides more complexity than simple transwell
systems and will provide more relevant data to support future in vivo studies. Successful completion of this Phase
I program will develop potentially two candidates with in vitro efficacy. This data will inform in vivo efficacy and
safety studies in a Phase II program where we will combine our novel BBB transporter sdAb with Abilita Bio’s
AD therapeutic that is currently under investigation. Ultimately, the development of this BBB transporter has the
potential to improve AD patient outcomes.

## Key facts

- **NIH application ID:** 10254514
- **Project number:** 1R43AG073065-01
- **Recipient organization:** ABILITA BIO, INC.
- **Principal Investigator:** Mauro Mileni
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $432,856
- **Award type:** 1
- **Project period:** 2021-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10254514

## Citation

> US National Institutes of Health, RePORTER application 10254514, Discovery of Novel Blood-Brain Barrier Targeting Antibodies for the Treatment of Alzheimer's Disease (1R43AG073065-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10254514. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*