Background: Recombinant antibody fragments are promising alternatives to full-length
immunoglobulins and offer important advantages compared with conventional monoclonal
antibodies: extreme specificity, higher affinity, superior stability and solubility, reduced immunogenicity
as well as easy and inexpensive large-scale production.
Objective: In this article we will review and discuss recombinant antibodies that are being evaluated
for neurodegenerative diseases in pre-clinical models and in clinical studies and will summarize new
strategies that are being developed to optimize their stability, specificity and potency for advancing
Methods: Articles describing recombinant antibody fragments used for neurological diseases were
selected (PubMed) and evaluated for their significance.
Results: Different antibody formats such as single-chain fragment variable (scFv), single-domain
antibody fragments (VHHs or sdAbs), bispecific antibodies (bsAbs), intrabodies and nanobodies, are
currently being studied in pre-clinical models of cancer as well as infectious and autoimmune
diseases and many of them are being tested as therapeutics in clinical trials. Immunotherapy
approaches have shown therapeutic efficacy in several animal models of Alzheimer´s disease (AD),
Parkinson disease (PD), dementia with Lewy bodies (DLB), frontotemporal dementia (FTD),
Huntington disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis
(MS). It has been demonstrated that recombinant antibody fragments may neutralize toxic extra- and
intracellular misfolded proteins involved in the pathogenesis of AD, PD, DLB, FTD, HD or TSEs
and may target toxic immune cells participating in the pathogenesis of MS.
Conclusion: Recombinant antibody fragments represent a promising tool for the development of
antibody-based immunotherapeutics for neurodegenerative diseases.