# Non-toxic CNS drug delivery across the BBB in Alzheimer's and other dementias

> **NIH NIH R41** · SOMATOCEUTICS, LLC · 2024 · $474,531

## Abstract

Project Summary
Alzheimer’s disease (AD) is the principal cause of dementia worldwide with its incidence anticipated to double
every 20 years as the population ages. It represents an ongoing public health crisis, compounded by the lack of
effective therapeutics to attenuate or reverse its progression. The principal obstacles to treatment are the inability
of drugs to penetrate the blood brain barrier (BBB) and their potential to cause adverse effects when administered
systemically. The unmet need of effective drug delivery systems for AD and AD-related dementias (ADRD) led
to the application of a variety of nanomaterials including carbon-based nanotubes and intranasal delivery
systems in order to encapsulate noxious drugs during their delivery and reduce drug toxicity. Unfortunately, many
of these alternatives, like carbon nanotubes, are themselves toxic, reducing their applicability. To surmount these
obstacles, Somatoceutics, LLC aims to utilize nanotechnology to apply materials, functionalized structures or
devices having novel properties in order to generate tools that may serve as new diagnostics, therapeutics and
preventatives. To this end, we identified a natural peptide-based nanomaterial derived from the C-terminal 41
residues of insulin-like growth factor binding protein-2 (IGFBP2 residues 249-289), which we named SMC-101
nanotubes (NTs). We have shown that SMC-101 peptides self-assemble into NTs that are 35 nm wide by 10 –
1,000 nm long driven by disulfide bond formation. They are stable and can be loaded with drugs such as
doxorubicin for cell delivery mediated by an intrinsic RGD motif, targeting them to integrins. Thus, SMC-101 NTs
represent natural, peptide-based drug delivery agents that provide a safe, non-toxic advantage over current
nanoparticles for delivery of drugs across the BBB. In this Phase I proof of principle application we hypothesize
that SMC-101 NTs will exhibit high stability and the ability to transcytose the BBB endothelium for efficient CNS
penetration. The objective of this application is to demonstrate the in vitro and in vivo effectiveness of SMC-101
NTs by completing the following two Specific Aims. The goal of AIM 1 is to optimize and standardize SMC-101
NT assembly, drug-loading, and BBB transcytosis in vitro. We will standardize SMC-101 NT assembly to
generate 100 nm long NTs. Immortalized human hCMEC3/D3 endothelial cells on Transwell inserts will be used
to demonstrate SMC-101 NT transcytosis as a model of the BBB. RGD-dependence for SMC-101 NT cellular
uptake and transcytosis will be determined. In AIM 2 we will evaluate the toxicity of SMC-101 NTs in mice and
their ability to deliver galantamine (GAL) to the CNS. We will compare the effectiveness of SMC-101 NT
encapsulated vs. “free” GAL in improving CNS penetration. These studies will provide strong proof of principle
demonstrating the efficacy of SMC-101 NTs as drug delivery agents for the treatment of AD. This will establish
SMC-101 NTs as safe, ef...

## Key facts

- **NIH application ID:** 10920948
- **Project number:** 1R41AG079748-01A1
- **Recipient organization:** SOMATOCEUTICS, LLC
- **Principal Investigator:** STEVEN Alan ROSENZWEIG
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $474,531
- **Award type:** 1
- **Project period:** 2024-09-25 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10920948

## Citation

> US National Institutes of Health, RePORTER application 10920948, Non-toxic CNS drug delivery across the BBB in Alzheimer's and other dementias (1R41AG079748-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10920948. Licensed CC0.

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