Immunotherapies for Neurodegenerative Diseases

Abstract

The current treatments for neurodegenerative diseases are mostly symptomatic without affecting the underlying cause of disease. Emerging evidence supports a potential role for immunotherapy in the management of disease progression. Numerous reports raise the exciting prospect that either the immune system or its derivative components could be harnessed to fight the misfolded and aggregated proteins that accumulate in several neurodegenerative diseases. Passive and active vaccinations using monoclonal antibodies and specific antigens that induce adaptive immune responses are currently under evaluation for their potential use in the development of immunotherapies. In this review, we aim to shed light on prominent immunotherapeutic strategies being developed to fight neuroinflammation-induced neurodegeneration, with a focus on innovative immunotherapies such as vaccination therapy.

Peptide-Based Vaccines for Neurodegenerative Diseases: Recent Endeavors and Future Perspectives

“…Thus, PrP rather than individual disease-associated proteins might be (immuno)therapeutically targeted. Moreover, a few additional molecular targets have been reported in the literature, e.g., TAR DNA-binding protein 43 (TDP-43), dipeptide repeat proteins (DPRs), superoxide dismutase 1, and huntingtin protein [1,14,18,31,32], but little data on the development of vaccines against these targets are available. [3].…”

“…Second-generation Aβ vaccines that have subsequently been tested in clinical trials (Table 1) include CAD106, ACC-001 (vanutide cridificar), Lu AF20513, UB-311, ACI-24, V-950, ABvac40, AD01, AD02, and AD03 [3][4][5]14,61,62]. CAD106 [1,[3][4][5]14,[61][62][63][64] is based on the first 6 amino acids of Aβ, ACC-001 [1,3,5,14,61,62,65] is based on the first 7 amino acids, Lu AF20513 [3][4][5]61,62] is based on the first 12 amino acids, UB-311 [3][4][5]14,61,62,66] is based on the first 14 amino acids, and ACI-24 [1,3,5,14,61,62] is based on the first 15 amino acids, whereas V-950 also employs an N-terminal Aβ peptide fragment [3,61,62], reported to be Aβ(1-15) [66]. On the other hand, it should be noticed that ABvac40 vaccine [1,…”

“…The most common neurodegenerative disease is Alzheimer's disease (AD), while other well-known neurodegenerative diseases include Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), etc. [1].…”

“…In addition to the extracellular amyloid plaques composed of Aβ, AD is also characterized by the formation of intracellular neurofibrillary tangles composed of the microtubule-associated protein tau in an abnormally phosphorylated form [11]. Thus, abnormal Aβ and tau aggregates have been considered the most typical characteristic of AD [1,12]. Though it is not clear how these aberrant oligomers/aggregates can lead to neurodegeneration, synaptic dysfunction and neuroinflammation they seem to cause might be the reason [13,14].…”

“…In addition to PD, α-syn has been lately associated with AD, too [17]. Misfolding/accumulation of additional proteins, e.g., superoxide dismutase 1 and huntingtin, in specific brain regions has been related to the onset/progress of neurodegenerative diseases, such as ALS and HD, respectively [1,14,18]. To further support the linkage between certain proteins/peptides and neurodegenerative diseases, focusing on AD, we should mention that cerebrospinal fluid (CSF) levels of Aβ-and tau-related biomarkers have been widely employed for confirming AD diagnosis, along with positive amyloid-PET scans [5,19].…”