Neurodegenerative Summaries

A biomarker to monitor CNS efficacy of 2-hydroxypropyl-β-cyclodextrin (HPBCD)
Ory, Daniel
T-012136

— Background: Niemann-Pick type C1 (NPC1) disease is a rare neurological disorder characterized by cholesterol and lipid accumulation in the central nervous system. Individuals with the abnormal buildup of cholesterol and other lipids in the brain often suffer from cognitive and movement difficulties,…

Neural interface device for complex, specific stimulation of peripheral nerves
Christiansen, Blaine ; MacEwan, Matthew ; Moran, Daniel
T-007621

— Technology Description This technology is patented bipolar sieve electrode designed to stimulate peripheral nerves in a specific direction and thereby expand the potential of using this type of neural interface device in clinical applications such as nerve regeneration and prosthetics. Sieve elec…

Novel bile acids as biomarkers for Niemann-Pick type C disease
Jiang, Xuntian ; Ory, Daniel
T-014292

— Technology Description Researchers at Washington University have developed and validated a set of bile acid biomarkers to screen, diagnose, and monitor the progression of Niemann-Pick disease type C (NPC), a genetic lysosomal storage disorder resulting from a defect in lipid transport. Previous ef…

MRI-based Alzheimer’s disease biomarkers for early diagnosis and clinical trials
Yablonskiy, Dmitriy ; Zhao, Yue
T-015754

— Technology Description Researchers in Prof. Dmitriy Yablonskiy’s laboratory have developed patented neuroimaging techniques to identify pre-clinical and early stage Alzheimer’s disease (AD) using MRI-based biomarkers of amyloid accumulation and other pathological changes in the brain. …

PET tracers for detection of early stage Alzheimer’s disease
Guruswami, Sundaram ; Sharma, Vijay ; Sivapackiam, Jothilingam
T-013525

— Technology Description Researchers at Washington University in St. Louis have developed PET radiotracers to image amyloid beta (A-beta) at early stages of Alzheimer’s Disease (AD). For AD treatment to be effective, it may have to be administered during the preclinical stage. As such, there i…

Neural interface device for complex, specific stimulation of peripheral nerves
Christiansen, Blaine ; MacEwan, Matthew ; Moran, Daniel
T-007621

— Technology Description This technology is patented bipolar sieve electrode designed to stimulate peripheral nerves in a specific direction and thereby expand the potential of using this type of neural interface device in clinical applications such as nerve regeneration and prosthetics. Sieve elec…

Biomarkers for Alzheimer’s Disease and Brain Injury
Ladenson, Jack ; Landt, Yvonne ; Laterza, Omar ; Modur, Vijay
T-004414

— Technology Description Researchers in Prof. Jack Ladenson’s laboratory have discovered biomarkers and associated antibodies for Alzheimer’s disease (AD) that could be used for early/presymptomatic diagnosis or in clinical trials for AD drugs. This patented technology is based on the i…

NMDA receptor modulator for neuroprotection after a stroke
Mennerick, Steven ; Sun, Min-Yu ; Taylor, Amanda ; Zorumski, Charles
T-016328

— Disease indication – neuroprotection in stroke/ischemia with potential for treating other neurodegenerative diseases Drug format – neurosteroid Drug class – drug repurposing (25-hydroxycholesterol) Research stage and Preliminary data: In vitro – The inventors demonstrated…

MicroRNA-induced Direct Conversion of Human Adult Fibroblasts into Neurons
Abernathy, Daniel ; Yoo, Andrew
T-017136

— Background: Studying late-onset neurodegenerative disorders using patient-specific neurons is one of the primary goals of precision medicine. The ability to generate human neurons that mimic the neurons of elderly individuals will provide an instrumental platform to model and study adult-onset neuro…

Sensitive and Accurate Mass Spec-based assay for simultaneous quantification of glycosylsphingosine and galactosylsphingosine
Jiang, Xuntian ; Ory, Daniel
T-016077

— Background Gaucher and Krabbe disease are two types of lipid (fat) storage diseases that can result in progressive damage to the nervous system and other organ systems. Together, these diseases affect about 450,000 people worldwide. In both of these diseases, there is an undesirable accumulation of…

Neurofibromin/dopamine signaling as a biomarker for cognitive and behavioral problems in children with neurofibromatosis type 1 (NF1)
Anastasaki, Corina ; Gutmann, David
T-015422

— Background: Neurofibromatosis type 1 (NF1) is a common neurological condition affecting roughly 1 in every 2,500 individuals. NF1 is associated with a host of clinical presentations, including malignant tumors and cognitive defects ranging from attention deficits, mental retardation, and autism. The…

Manipulating Tricellular Junction Permeability in Blood Brain Barrier to Treat Brain Tumors
Gong, Yong-feng ; Hou, Jianghui
T-017092

— Background: Brain tumors are the most lethal disease known to mankind with approximately 170,000 annual diagnoses and 13,000 deaths attributed to brain cancer. Glioblastoma, the most common and aggressive, has a median survival of approximately 18 months. Chemotherapeutic agents have been approved b…

Therapeutic Approach for Huntington’s Disease (HD)
Kim, Albert ; Yano, Hiroko
T-016079

— Dr. Hiroko Yano and Dr. Albert Kim, and their research teams at the Washington University School of Medicine in St. Louis developed and extensively evaluated a novel therapeutic approach using DNMT inhibitors to treat Huntington’s Disease (HD) and other neurodegenerative disorders. Currently D…

Modulation of the DLK/JNK Pathway as a Method for Inhibiting Axonal Degeneration
DiAntonio, Aaron ; Milbrandt, Jeffrey ; Miller, Bradley ; Press, Craig
T-008422

— Background: Axonal degeneration is a feature commonly associated with many neuropathological conditions including response to injury, exposure to neurotoxins, hereditary neuropathies, glaucoma, and neurodegenerative diseases. The degenerative process is active when neuronal insults trigger a self-de…

Tri-heterocyclic ring compounds as alpha-synuclein ligands
Kotzbauer, Paul ; Mach, Robert ; Tu, Zhude "Will" ; Yu, Lihai
T-011942

— A novel series of phenothiazine-derived molecules are useful for detecting Parkinson’s disease using positron emission tomography (PET) imaging. The molecules bind with high affinity to the alpha- synuclein protein, which forms aggregates in the brain and is associated with the neurodegenerati…

microRNA biomarker and drug target for ALS and other motor neuron diseases
Dougherty, Joseph ; Hoye, Mariah ; Hyman, Theodore ; Koval, Erica ; Miller, Timothy
T-015167

— Prof. Timothy Miller and colleagues have identified a motor neuron-specific, drug responsive microRNA (miR-218) that reflects the pathology of amyotrophic lateral sclerosis (ALS). This biomarker could be a target for therapeutic intervention or a proxy for motor neuron health and survival, including…

A companion diagnostic to SARM1 inhibitors for neurodegenerative diseases
Bloom, Adam ; DiAntonio, Aaron ; Mao, Xianrong ; Milbrandt, Jeffrey
T-019378

— Technology Description Researchers at Washington University, led by Jeffrey Milbrandt, have developed a companion diagnostic for SARM1 inhibitors that detects pathogenic variants of the SARM1 gene. Patients with one of several identified variants of SARM1 would respond well to SARM1 inhibitor thera…

Automated image processing tools for quantitative SPECT and PET scans
Jha, Abhinav Kumar ; Liu, Ziping ; Moon, Hae Sol ; Rahman, Md Ashequr ; Yu, Zitong
T-019331

— Engineers in Washington University’s Computational Medical Imaging Lab have developed automated, machine-learning techniques to improve nuclear medicine imaging (SPECT and PET). These tools include estimation-based segmentation methods to define boundaries and ASC (attenuation and scatter comp…

Eye test to diagnose preclinical Alzheimer’s disease
Apte, Rajendra ; Van Stavern, Gregory
T-018518

— Technology Description Researchers at Washington University in St. Louis have developed a non-invasive screening method using optical coherence tomography angiography (OCTA) to detect Alzheimer’s disease (AD) at the early, preclinical stage. AD is characterized by progressive memory loss, be…

Blood-based biomarkers of Alzheimer’s disease for diagnostics and clinical trials
Cruchaga, Carlos ; Dube, Umber ; Ibanez, Laura
T-019198

— Technology Description: Researchers in Prof. Carlos Cruchaga’s laboratory have identified a sensitive and specific panel of circular RNAs (circRNA) that could be used for diagnosing, screening or monitoring patients with Alzheimer’s disease. The expression of these circRNAs tracks with …

Treatments for Wolfram syndrome
Clark, Amy ; Mahadevan, Jana ; Urano, Fumihiko
T-015862

— Technology Description Dr. Fumihiko Urano at Washington University in St. Louis (WUSTL) and colleagues have developed therapeutic strategies to treat Wolfram syndrome. Wolfram syndrome is a rare, life-threating, genetic disorder characterized by insulin-dependent diabetes mellitus, diabetes insipi…

Plasma oxysterols as biomarkers for Niemann-Pick C disease
Ory, Daniel
T-007594

— Background Niemann-Pick type C is a rare, progressive neurodegenerative disease characterized by accumulation of cholesterol and other lipids in the viscera and central nervous system. For cases caused by mutations in the NPC1 or NPC2 gene, egress of lipids from endosomes or lysosomes are impaired, resulting in clinical symptoms such as abnormal eye movements, hearing loss, cerebellar ataxia, difficulty swallowing, and cognitive impairment. However, patients with Neimann-Pick disease have highly variable clinical presentation and symptom progression, making diagnosis challenging. Technology Summary A panel of oxygenated forms of cholesterol (oxysterols) in plasma that can be used as a diagnostic test for Neimann-Pick type C1 disease. The mass spectrometry-based panel is able to discriminate between subjects with NPC1 and normal control subjects. The oxysterol biomarkers have clinical utility in newborn screening for early diagnosis of NP1C disease, as markers for disease severity, and as biomarkers to aid in evaluation of new therapies for NPC1. Key Advantages High sensitivity Rapid diagnostic for screening infants Patents US 8,497,122 Issued US 9,012,216 Issued Publications Porter et al., 2010 – Cholesterol oxidation products are sensitive and specific blood-based biomarkers for NPC1 disease.

Alpha-synuclein ligands as specific PET imaging probes for Parkinson’s Disease and other disorders
Dhavale, Dhruva ; Kotzbauer, Paul ; Tu, Zhude "Will" ; Yue, Xuyi
T-018038

— Technology Description A team of researchers at Washington University have developed and optimized highly potent PET imaging probes which are specific for the misfolded protein that is the hallmark of Parkinson’s disease and related disorders. This family of molecules was designed based on s…

microRNA biomarker and drug target for ALS and other motor neuron diseases
Dougherty, Joseph ; Hoye, Mariah ; Hyman, Theodore ; Koval, Erica ; Miller, Timothy
T-015167

— Prof. Timothy Miller and colleagues have identified a motor neuron-specific, drug responsive microRNA (miR-218) that reflects the pathology of amyotrophic lateral sclerosis (ALS). This biomarker could be a target for therapeutic intervention or a proxy for motor neuron health and survival, including…

Drugs to supplement microglial metabolism during treatment of Alzheimer’s disease
Colonna, Marco ; Ulland, Tyler
T-017401

— Background: Alzheimer’s disease (AD) is the 6th leading cause of death in the United States, and yet causation of the disease is poorly understood and targets for therapeutic intervention are still being identified. Recently, mutations in the immune receptor TREM2 have been found to be strongl…

Tri-heterocyclic ring compounds as alpha-synuclein ligands
Kotzbauer, Paul ; Mach, Robert ; Tu, Zhude "Will" ; Yu, Lihai
T-011942

— A novel series of phenothiazine-derived molecules are useful for detecting Parkinson’s disease using positron emission tomography (PET) imaging. The molecules bind with high affinity to the alpha- synuclein protein, which forms aggregates in the brain and is associated with the neurodegenerati…

Therapeutic targeting of LDL in ALS
Kreple, Collin ; Miller, Timothy ; Nielsen, Susan ; Racette, Brad
T-020021

— Technology Description Researchers in Brad Racette and Tim Miller’s labs at Washington University have developed a therapeutic strategy for treating ALS by using statins to lower LDL. Statins were successful at prolonging both survival and time with a normal gait. The researchers identif…

Lightweight, wearable cap for bedside functional optical neuroimaging
Bergonzi, Karla ; Culver, Joseph ; Eggebrecht, Adam ; Ferradal, Silvina
T-013611

— Technology Description Researchers in Prof. Joseph Culver’s laboratory have developed a patented, compact, lightweight functional neuroimaging device for long-term bedside monitoring. This technology, based on high-density diffuse optical tomography (HD-DOT), could be used as a surrogate for …

Robust, scalable phase control system for non-invasive neuromodulation devices
Li, Jr-Shin ; Zlotnik, Anatoly
T-016206

— Technology Description: Researchers in Prof. Jr-Shin Li’s laboratory have developed a robust, scalable, patented technology to control and entrain complex, noisy, non-linear oscillating systems such as neuronal firing and circadian rhythms. This system uses a single global, open-loop control …

Sigma-1 targeted PET tracers
Mach, Robert ; Tu, Zhude "Will" ; Wang, Wei
T-010394

— Technology Description Researchers at Washington University in St. Louis and their colleagues have developed positron emission tomography (PET) tracers with high affinity for sigma-1 receptors. Sigma receptors have two subtypes, sigma-1 and sigma-2. Sigma-1 has high expression in the limbic and mo…

Drug target and biomarker for multiple sclerosis
Klein, Robyn ; Williams, Jessica
T-017623

— Technology Description Researchers in Prof. Robyn Klein’s laboratory have discovered that interferon lambda (IFN-λ) is a potential target for treating multiple sclerosis (MS), particularly secondary progressive MS (SPMS). Most patients with MS present with relapsing remitting MS (RRM…

Design and Development of Organomedicinals for Imaging and Treatment of Amyotrophic Lateral Sclerosis and Frontotemporal Dementia (FTD)
Guruswami, Sundaram ; Sharma, Vijay ; Sivapackiam, Jothilingam
T-016665

— Background Frontotemporal Dementia (FTD) is the second most common form of non-Alzheimer’s dementia in the population under 65 years old. FTD represents approximately 20% of all dementias and onset normally appears in the mid to late 50s. Clinically FTD is characterized by a progressive neur…

Sulfur-containing compounds targeting on vesicular acetylcholine transporter for cognitive function
Jin, Hongjun ; Liu, Hui ; Luo, Zonghua ; Tu, Zhude "Will"
T-016517

— Background: Dementia caused by Alzheimer’s disease, Parkinson’s disease, and other neurodegenerative diseases manifests as a progressive decline in memory and other cognitive abilities. Deposits of beta-amyloid plaques and tangles of the tau protein are thought to cause the destruction o…

Multi-Parametric Imaging of Tumor Heterogeneity Using Noninvasive, Non-radiative Water Diffusion
Benzinger, Tammie ; Guzman, Gloria ; Wang, Qing ; Wang, Yong
T-016652

— Background Currently, biopsies are the only definitive method to diagnose a brain tumor. While PET-CT is used for initial imaging and monitoring of the tumor, after completion of treatments, a 6-8-week delay is usually implemented to avoid false-positive results. Yet, the delay could also result in…

Novel human astrovirus sequences for diagnostics and vaccine development for encephalitis and gastroenteritis
Finkbeiner, Stacy ; Virgin, Herbert ; Wang, David ; Zhao, Guoyan
T-009294

— Technology Description A team of researchers at Washington University and the Centers for Disease Control discovered, sequenced and patented a novel human astrovirus that can cause encephalitis and gastroenteritis (non-etiologic diarrhea), offering a path to detection and diagnostics. The virus (…

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