scholarly journals Antisense Drugs Make Sense for Neurological Diseases

2021 ◽  
Vol 61 (1) ◽  
pp. 831-852
Author(s):  
C. Frank Bennett ◽  
Holly B. Kordasiewicz ◽  
Don W. Cleveland
Keyword(s):  
Neurodegenerative Diseases ◽  
Rna Splicing ◽  
Genetic Basis ◽  
Neurological Diseases ◽  
Intrathecal Injection ◽  
Long Term Effects ◽  
New Class ◽  
Therapeutic Platform ◽  
Lateral Sclerosis

The genetic basis for most inherited neurodegenerative diseases has been identified, yet there are limited disease-modifying therapies for these patients. A new class of drugs—antisense oligonucleotides (ASOs)—show promise as a therapeutic platform for treating neurological diseases. ASOs are designed to bind to the RNAs either by promoting degradation of the targeted RNA or by elevating expression by RNA splicing. Intrathecal injection into the cerebral spinal fluid results in broad distribution of antisense drugs and long-term effects. Approval of nusinersen in 2016 demonstrated that effective treatments for neurodegenerative diseases can be identified and that treatments not only slow disease progression but also improve some symptoms. Antisense drugs are currently in development for amyotrophic lateral sclerosis, Huntington's disease, Alzheimer's disease, Parkinson's disease, and Angelman syndrome, and several drugs are in late-stage research for additional neurological diseases. This review highlights the advances in antisense technology as potential treatments for neurological diseases.

scholarly journals Antisense Oligonucleotide Therapies for Neurodegenerative Diseases

2019 ◽  
Vol 42 (1) ◽  
pp. 385-406 ◽  
Author(s):  
C. Frank Bennett ◽  
Adrian R. Krainer ◽  
Don W. Cleveland
Keyword(s):  
Neurodegenerative Diseases ◽  
Spinal Muscular Atrophy ◽  
Antisense Oligonucleotide ◽  
Antisense Oligonucleotides ◽  
Muscular Atrophy ◽  
Neurological Diseases ◽  
Great Promise ◽  
Disease Symptoms ◽  
Therapeutic Platform ◽  
Lateral Sclerosis

Antisense oligonucleotides represent a novel therapeutic platform for the discovery of medicines that have the potential to treat most neurodegenerative diseases. Antisense drugs are currently in development for the treatment of amyotrophic lateral sclerosis, Huntington's disease, and Alzheimer's disease, and multiple research programs are underway for additional neurodegenerative diseases. One antisense drug, nusinersen, has been approved for the treatment of spinal muscular atrophy. Importantly, nusinersen improves disease symptoms when administered to symptomatic patients rather than just slowing the progression of the disease. In addition to the benefit to spinal muscular atrophy patients, there are discoveries from nusinersen that can be applied to other neurological diseases, including method of delivery, doses, tolerability of intrathecally delivered antisense drugs, and the biodistribution of intrathecal dosed antisense drugs. Based in part on the early success of nusinersen, antisense drugs hold great promise as a therapeutic platform for the treatment of neurological diseases.

scholarly journals Multiscale Approximate Entropy for Gait Analysis in Patients with Neurodegenerative Diseases

Entropy ◽  
2019 ◽  
Vol 21 (10) ◽  
pp. 934
Author(s):  
An-Bang Liu ◽  
Che-Wei Lin
Keyword(s):  
Neurodegenerative Diseases ◽  
Diagnostic Marker ◽  
Neurological Diseases ◽  
Reaction Force ◽  
Approximate Entropy ◽  
Parkinson’S Diseases ◽  
Gait Abnormalities ◽  
The Right ◽  
Lateral Sclerosis

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS), Parkinson’s diseases (PD), and Huntington’s disease (HD) are not rare neurological diseases. They affect different neurological systems and present various characteristic gait abnormalities. We retrieved gait signals of the right and left feet from a public domain on the Physionet. There were 13 patients with ALS, 15 patients with PD, 20 patients with HD and 16 healthy controls (HC). We used multiscale approximate entropy (MAE) to analyze ground reaction force on both feet. Our study shows that MAE increases with scales in all tested subjects. The group HD has the highest MAE and group ALS has the lowest MAE. We can differentiate ALS from HC by MAE, while scale factors >10 in the left foot. There are few significant differences of MAE between the HC and HD. We found a good correlation of MAE between both feet in group ALS. In conclusion, our results indicate that MAE analysis of gait signals can be used for diagnosis and long-term assessment for ALS and probably HD. Similarity of MAE between both feet can also be a diagnostic marker for ALS.

Traumatic brain injury: a risk factor for neurodegenerative diseases

2016 ◽  
Vol 27 (1) ◽  
pp. 93-100 ◽  
Author(s):  
Rajaneesh Gupta ◽  
Nilkantha Sen
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Chronic Traumatic Encephalopathy ◽  
Disease Process ◽  
Acute Effects ◽  
Secondary Progressive ◽  
Lateral Sclerosis

AbstractTraumatic brain injury (TBI), a major global health and socioeconomic problem, is now established as a chronic disease process with a broad spectrum of pathophysiological symptoms followed by long-term disabilities. It triggers multiple and multidirectional biochemical events that lead to neurodegeneration and cognitive impairment. Recent studies have presented strong evidence that patients with TBI history have a tendency to develop proteinopathy, which is the pathophysiological feature of neurodegenerative disorders such as Alzheimer disease (AD), chronic traumatic encephalopathy (CTE), and amyotrophic lateral sclerosis (ALS). This review mainly focuses on mechanisms related to AD, CTE, and ALS that are induced after TBI and their relevance to the advancement of these neurodegenerative diseases. This review encompasses acute effects and chronic neurodegenerative consequences after TBI for a better understanding of TBI-induced neuronal death and to design therapies that will effectively treat patients in the primary or secondary progressive stages.

The Influence of Vitamin D on Neurodegeneration and Neurological Disorders: A Rationale for its Physio-pathological Actions

2020 ◽  
Vol 26 (21) ◽  
pp. 2475-2491 ◽  
Author(s):  
Maria Morello ◽  
Massimo Pieri ◽  
Rossella Zenobi ◽  
Alessandra Talamo ◽  
Delphine Stephan ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Vitamin D ◽  
Neurodegenerative Diseases ◽  
Neurological Disorders ◽  
Neurological Diseases ◽  
Steroid Hormone ◽  
Neuroactive Steroid ◽  
Brain Functions ◽  
Prevention And Treatment ◽  
Lateral Sclerosis

Vitamin D is a steroid hormone implicated in the regulation of neuronal integrity and many brain functions. Its influence, as a nutrient and a hormone, on the physiopathology of the most common neurodegenerative diseases is continuously emphasized by new studies. This review addresses what is currently known about the action of vitamin D on the nervous system and neurodegenerative diseases such as Multiple Sclerosis, Alzheimer’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis. Further vitamin D research is necessary to understand how the action of this “neuroactive” steroid can help to optimize the prevention and treatment of several neurological diseases.

Rodent models of early environment effects on offspring development and susceptibility to neurological diseases in adulthood

2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Laurence Coutellier
Keyword(s):  
Environmental Conditions ◽  
Developmental Plasticity ◽  
Neurological Diseases ◽  
Adult Life ◽  
Later Life ◽  
Long Term Effects ◽  
Early Environment ◽  
Offspring Development ◽  
Early Life Events

AbstractEvents early in life can program brain for a pattern of neuroendocrine and behavioral responses in later life. This mechanism is named “developmental phenotypic plasticity”. Experimental evidences from rodents show that early experiences influence long-term development of behavioral, neuroendocrine and cognitive functions. While some neonatal conditions lead to positive outcomes, offspring might also display neurological dysfunctions in adulthood in case of adverse conditions during the early development. Different factors have been suggested to mediate the effects of neonatal conditions on offspring development but their exact contribution as well as their interaction still needs to be clarified. Studies based on rodents have been developed to model the long-term effects of early environmental conditions on the developing brain. These studies highlight importance of maternal behavior in mediating the effects of early environmental conditions on the offspring. However, other studies suggest that aside from the level of maternal care, other factors (gender, neonatal glucocorticoid levels) contribute to the adjustment of offspring phenotype to early environmental cues. Altogether, rodents-based evidence suggests that developmental plasticity is a very complex phenomenon mediated by multiple factors that interact one to each other. Ultimately, the goal is to understand how early life events can lead to advantageous phenotype in adult life, or, on the contrary, can predispose individuals to psychopathologies such as depression or anxiety.

scholarly journals Lasting Effects of Intrauterine Exposure to Preeclampsia on Offspring and the Underlying Mechanism

2019 ◽  
Vol 09 (03) ◽  
pp. e275-e291 ◽  
Author(s):  
Hui Qing Lu ◽  
Rong Hu
Keyword(s):  
Clinical Management ◽  
Neurological Diseases ◽  
Large Body ◽  
Underlying Mechanism ◽  
Pregnancy Complication ◽  
Adverse Impact ◽  
Long Term Effects ◽  
Epidemiological Evidence ◽  
Short Term

AbstractPreeclampsia is a common pregnancy complication which can have adverse impact on both mother and baby. In addition to the short term effects, a large body of epidemiological evidence has found preeclampsia can exert long-lasting effects on mother and offspring. Studies suggest that offspring exposed to preeclampsia are at a higher risk of developing cardiovascular, metabolic, and neurological diseases, as well as other diseases. However, studies investigating the underlying mechanism are limited, the exact mechanism still remains unclear. In this study, we will review the epidemiological evidence and studies exploring the mechanism underlying long-term effects of preeclampsia on offspring. Further studies should be targeted at this field so as to implement effective clinical management to prevent the exposed offspring from potential diseases.

Long-term effects of edaravone on patients with amyotrophic lateral sclerosis

2017 ◽  
Vol 381 ◽  
pp. 572
Author(s):  
M. Okada ◽  
H. Ueyama ◽  
M. Ishizaki ◽  
Y. Maeda ◽  
S. Yamashita ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Long Term Effects ◽  
Lateral Sclerosis

scholarly journals Salivary Biomarkers: Future Approaches for Early Diagnosis of Neurodegenerative Diseases

2020 ◽  
Vol 10 (4) ◽  
pp. 245
Author(s):  
Giovanni Schepici ◽  
Serena Silvestro ◽  
Oriana Trubiani ◽  
Placido Bramanti ◽  
Emanuela Mazzon
Keyword(s):  
Early Diagnosis ◽  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Neuronal Degeneration ◽  
Neurological Diseases ◽  
Alpha Synuclein ◽  
Future Studies ◽  
Salivary Biomarkers ◽  
Biological Liquids ◽  
Lateral Sclerosis

Many neurological diseases are characterized by progressive neuronal degeneration. Early diagnosis and new markers are necessary for prompt therapeutic intervention. Several studies have aimed to identify biomarkers in different biological liquids. Furthermore, it is being considered whether saliva could be a potential biological sample for the investigation of neurodegenerative diseases. This work aims to provide an overview of the literature concerning biomarkers identified in saliva for the diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Specifically, the studies have revealed that is possible to quantify beta-amyloid1–42 and TAU protein from the saliva of AD patients. Instead, alpha-synuclein and protein deglycase (DJ-1) have been identified as new potential salivary biomarkers for the diagnosis of PD. Nevertheless, future studies will be needed to validate these salivary biomarkers in the diagnosis of neurological diseases.

scholarly journals Long-Term Effects of Myoinositol on Behavioural Seizures and Biochemical Changes Evoked by Kainic Acid Induced Epileptogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Lia Tsverava ◽  
Manana Kandashvili ◽  
Giorgi Margvelani ◽  
Tamar Lortkipanidze ◽  
Georgi Gamkrelidze ◽  
...  
Keyword(s):  
Kainic Acid ◽  
Neurological Diseases ◽  
Treatment Strategies ◽  
Biochemical Changes ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Molecular Changes ◽  
Acute Seizures ◽  
Spontaneous Recurrent Seizures

Epilepsy is one of the most devastating neurological diseases and despite significant efforts there is no cure available. Occurrence of spontaneous seizures in epilepsy is preceded by numerous functional and structural pathophysiological reorganizations in the brain—a process called epileptogenesis. Treatment strategies targeting this process may be efficient for preventing spontaneous recurrent seizures (SRS) in epilepsy, or for modification of disease progression. We have previously shown that (i) myoinositol (MI) pretreatment significantly decreases severity of acute seizures (status epilepticus: SE) induced by kainic acid (KA) in experimental animals and (ii) that daily post-SE administration of MI for 4 weeks prevents certain biochemical changes triggered by SE. However it was not established whether such MI treatment also exerts long-term effects on the frequency of SRS. In the present study we have shown that, in KA-induced post-SE epilepsy model in rats, MI treatment for 28 days reduces frequency and duration of behavioural SRS not only during the treatment, but also after its termination for the following 4 weeks. Moreover, MI has significant effects on molecular changes in the hippocampus, including mi-RNA expression spectrum, as well as mRNA levels of sodium-MI transporter and LRRC8A subunit of the volume regulated anionic channel. Taken together, these data suggest that molecular changes induced by MI treatment may counteract epileptogenesis. Thus, here we provide data indicating antiepileptogenic properties of MI, which further supports the idea of developing new antiepileptogenic and disease modifying drug that targets MI system.

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