Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2024 Apr 12;12(4):851.
doi: 10.3390/biomedicines12040851.

Transcytosis-Driven Treatment of Neurodegenerative Disorders by mRNA-Expressed Antibody-Transferrin Conjugates

Sarfaraz K Niazi  1 , Matthias Magoola  2
Affiliations
Review

Transcytosis-Driven Treatment of Neurodegenerative Disorders by mRNA-Expressed Antibody-Transferrin Conjugates

Sarfaraz K Niazi et al. Biomedicines. .

Abstract

The recent setbacks in the withdrawal and approval delays of antibody treatments of neurodegenerative disorders (NDs), attributed to their poor entry across the blood-brain barrier (BBB), emphasize the need to bring novel approaches to enhance the entry across the BBB. One such approach is conjugating the antibodies that bind brain proteins responsible for NDs with the transferrin molecule. This glycoprotein transports iron into cells, connecting with the transferrin receptors (TfRs), piggybacking an antibody-transferrin complex that can subsequently release the antibody in the brain or stay connected while letting the antibody bind. This process increases the concentration of antibodies in the brain, enhancing therapeutic efficacy with targeted delivery and minimum systemic side effects. Currently, this approach is experimented with using drug-transferring conjugates assembled in vitro. Still, a more efficient and safer alternative is to express the conjugate using mRNA technology, as detailed in this paper. This approach will expedite safer discoveries that can be made available at a much lower cost than the recombinant process with in vitro conjugation. Most importantly, the recommendations made in this paper may save the antibodies against the NDs that seem to be failing despite their regulatory approvals.

Keywords: aducanumab; antibodies; cinpanemab; donanemab; lecanemab; mRNA; nanobodies; neurological diseases; protein aggregates; protein misfolding.

PubMed Disclaimer

Conflict of interest statement

The authors are developers of mRNA therapies as executives of RNA Therapeutics, Inc., Deerfield, IL, USA. The mRNA sequence reported is part of several pending US patents held by the authors. None of the authors are paid employee of RNA Therapeutics, Inc.

Figures

Figure 1
Figure 1
The blood–brain barrier means expediting natural or induced transport as a therapeutic measure [shutterstock_2304653921 Licensed].
Figure 2
Figure 2
Transferrin-fused antibodies are transported across the BBB.
Figure 3
Figure 3
mRNA-based translation of proteins [Shutterstock license].
See this image and copyright information in PMC

Similar articles

See all similar articles

References

    1. Goedert M. Neurodegenration: Alzheimer’s and Parkinson’s diseases: The prion concept in relation to assembled Aβ, tau, and α-synuclein. Science. 2015;349:1255555. doi: 10.1126/science.1255555. - DOI - PubMed
    1. Bertram L., Tanzi R.E. The genetic epidemiology of neurodegenerative disease. J. Clin. Invest. 2005;115:1449–1457. doi: 10.1172/JCI24761. - DOI - PMC - PubMed
    1. Walsh D.M., Selkoe D.J. A critical appraisal of the pathogenic protein spread hypothesis of neurodegeneration. Nat. Rev. Neurosci. 2016;17:251–260. doi: 10.1038/nrn.2016.13. - DOI - PMC - PubMed
    1. Makin S. The amyloid hypothesis on trial. Nature. 2018;559:S4–S7. doi: 10.1038/d41586-018-05719-4. - DOI - PubMed
    1. Ross C.A., Tabrizi S.J. Huntington’s disease: From molecular pathogenesis to clinical treatment. Lancet Neurol. 2011;10:83–98. doi: 10.1016/S1474-4422(10)70245-3. - DOI - PubMed

Grants and funding

This research received no external funding.

LinkOut - more resources

-