Reagents against tau variants selectively present in human Alzheimer's disease or traumatic brain injury samples as biomarkers and therapeutics for neurodegenerative disease

Michael Sierks (Inventor)

Research output: Patent

Abstract

Misfolding and aggregation of proteins, such as beta-amyloid (A), alpha-synuclein (a-syn), tau and TAR DNA-binding protein 43 (TDP-43), have been strongly correlated with early onset of neurodegenerative diseases such as Alzheimer's Disease (AD), Parkinson's Disease (PD), Frontotemporal Dementia (FTD), amyotrophic lateral sclerosis (ALS) and other dementias as well as traumatic brain injury (TBI). Detection of specific variants of these proteins, such as the toxic oligomeric protein forms, have great promise as sensitive and dynamic biomarkers for neurodegenerative diseases and TBI. Researchers at Arizona State University have synthesized recombinant antibody fragments (nanobodies) for the treatment and early diagnosis of neurodegenerative diseases such as AD, PD, ALS, FTD, ALS and traumatic brain injury (TBI)-mediated neurodegeneration. These nanobodies specifically target toxic oligomeric protein variants but do not bind monomeric, fibrillar or non-disease associated forms. These nanobodies can be used for detecting the protein variants present in blood, CSF and other biological samples. These highly specific and selective nanobodies have great utility in diagnosing, staging, treating and imaging neurodegenerative diseases and TBI. Moreover, their very specific targeting minimizes unwanted side effects, and may provide for a safer long-term therapeutic. Potential Applications Detection, staging and treatment of misfolded toxic oligomeric protein forms present in neurodegenerative diseases: A, tau, TDP-43 & a-syn- Alzheimer's Disease, Parkinson's Disease, taupathies, FTD, ALS, TBI & other dementias Assessment of neuronal damage & treatment strategies following TBI Assess protein variants of A, tau, TDP-43 & a-syn at select times to identify the stage and severity of TBI Creation of an effective personalized treatment plan targeting the proteins as early possible to alter disease progression and future damage Benefits and Advantages Picomolar sensitivity Can readily distinguish between AD, PD, FTD, ALS, and cognitively normal samples and the stages of neurodegeneration Can detect severity of TBI Can be conjugated to an imaging agent Can be used in immunoassays for early stage diagnoses Specific to only the neurotoxic protein variants to minimize unwanted side effects Targets an early cause, rather than treating symptoms Well defined specificities and selectivities for selected protein forms to facilitate specific diagnoses Early diagnoses - well before onset of disease or mild-cognitive impairment Download Original PDF For more information about the inventor(s) and their research, please see Dr. Sierks' directory webpage Dr. Sierks' laboratory webpage
Original languageEnglish (US)
StatePublished - Oct 22 2015

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