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UA receives $37.5 million NIH grant to research potential regenerative therapy for Alzheimer's

Reviewed by James Ives, M.Psych. (Editor)Sep 6 2019

The University of Arizona Center for Innovation in Brain Science has received a $37.5 million grant from the National Institutes of Health to research a potential regenerative therapy for Alzheimer's disease.

A team led by Roberta Diaz Brinton, PhD, director of the Center for Innovation in Brain Science, received the multi-million dollar grant from the National Institute on Aging. The five-year grant will fund a national multi-site Phase 2 clinical trial to determine the effectiveness of allopregnanalone, or allo, as a treatment for individuals with early-stage Alzheimer's who carry the genetic risk factor for the disease. This award supports the goals of the National Alzheimer's Project Act.

Based on our discovery and early clinical research findings, we are optimistic that allo could be an effective treatment for Alzheimer's. Our precision medicine approach for Alzheimer's is designed to treat the right person at the right time. Specifically, our clinical trial of allo will focus on those with early-stage Alzheimer's who have the genetic risk factor for the disease. We are thrilled to advance allo as the first regenerative therapeutic for Alzheimer's and to bring innovations in the brain science of the future to those who need a cure today."

Roberta Diaz Brinton, PhD, director of the Center for Innovation in Brain Science, University of Arizona

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Assessment and Measurement of Spasticity in MS: State of the Evidence.

Author information

1Department of Neurology, Oregon Health & Science University, 3303 SW Sam Jackson Park Rd., L226, Portland, OR, 97239, USA. This email address is being protected from spambots. You need JavaScript enabled to view it. Portland Health Care System, 3710 SW US Veterans Hospital Rd., R&D 27, Portland, OR, 97239, USA. This email address is being protected from spambots. You need JavaScript enabled to view it.t of Neurology, Oregon Health & Science University, 3303 SW Sam Jackson Park Rd., L226, Portland, OR, 97239, USA.4VA MS Center of Excellence-West, VA Portland Health Care System, 3710 SW US Veterans Hospital Rd., Portland, OR, 97239, USA.

Abstract

PURPOSE OF REVIEW:

The purpose of this review is to familiarize the reader with assessments and measurement of spasticity in people with Multiple Sclerosis (MS). Spasticity affects 60-84% of people with MS, Worsening as disability worsens and impacting activity, participation, and quality of life. Spasticity manifests in many ways, including spasms, resistance to passive stretch, pain, and perception of tightness, and can affect muscles throughout the body, making assessment and quantification of spasticity challenging but important. Assessment tools include those quantified by clinicians, instrumentation, and patients.

RECENT FINDINGS:

Most tools for measuring spasticity are based on clinician scoring, were developed many years ago, and have undergone minimal recent advances. More recent developments are patient-reported outcome measures for spasticity, including the Numeric Rating Scale for Spasticity (NRS-S) and the disease-specific Multiple Sclerosis Spasticity Scale-88 (MSSS), and, most recently, imaging through elastography. MS-related spasticity is common and often disabling. There are various spasticity measurement tools available, each with advantages and limitations. Newer tools are likely to be developed as our understanding of spasticity in MS grows.

KEYWORDS:

Assessment; Measurement; Multiple Sclerosis; Outcomes; Spasticity
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Original author: Stuart
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Computational Drug Repurposing Algorithm Targeting TRPA1 Calcium Channel as a Potential Therapeutic Solution for Multiple Sclerosis.

Author information

1Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania.2Faculty of Pharmacy, "Carol Davila" University of Medicine and Pharmacy, Traian Vuia 6, 020956 Bucharest, Romania. This email address is being protected from spambots. You need JavaScript enabled to view it. for Physiology and Pharmacology, Medical University of Vienna, Schwarzspanierstrasse 17, 1090 Vienna, Austria.

Abstract

Multiple Sclerosis (MS) is a chronic autoimmune disease affecting the central nervous system (CNS) through neurodegeneration and demyelination, leading to physical/cognitive disability and neurological defects. A viable target for treating MS appears to be the Transient Receptor Potential Ankyrin 1 (TRPA1) calcium channel, whose inhibition has been shown to have beneficial effects on neuroglial cells and protect against demyelination. Using computational drug discovery and data mining methods, we performed an in silico screening study combining chemical graph mining, quantitative structure-activity relationship (QSAR) modeling, and molecular docking techniques in a global prediction model in order to identify repurposable drugs as potent TRPA1 antagonists that may serve as potential treatments for MS patients. After screening the DrugBank database with the combined generated algorithm, 903 repurposable structures were selected, with 97 displaying satisfactory inhibition probabilities and pharmacokinetics. Among the top 10 most probable inhibitors of TRPA1 with good blood brain barrier (BBB) permeability, desvenlafaxine, paliperidone, and febuxostat emerged as the most promising repurposable agents for treating MS. Molecular docking studies indicated that desvenlafaxine, paliperidone, and febuxostat are likely to induce allosteric TRPA1 channel inhibition. Future in vitro and in vivo studies are needed to confirm the biological activity of the selected hit molecules.
PMID: 31480671 DOI: 10.3390/pharmaceutics11090446

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Original author: Stuart
  650 Hits
650 Hits