scholarly journals Emerging Oligonucleotide Therapeutics for Rare Neuromuscular Diseases

2021 ◽  
pp. 1-16
Author(s):  
Yoshitsugu Aoki ◽  
Matthew J.A. Wood
Keyword(s):  
Rare Diseases ◽  
Neuromuscular Diseases ◽  
Exon Skipping ◽  
Rare Condition ◽  
Regulatory Agencies ◽  
Ribonucleic Acids ◽  
Rna Transcripts ◽  
The Usa ◽  
Target Rna

Research and drug development concerning rare diseases are at the cutting edge of scientific technology. To date, over 7,000 rare diseases have been identified. Despite their individual rarity, 1 in 10 individuals worldwide is affected by a rare condition. For the majority of these diseases, there is no treatment, much less cure; therefore, there is an urgent need for new therapies to extend and improve quality of life for persons who suffer from them. Here we focus specifically on rare neuromuscular diseases. Currently, genetic medicines using short antisense oligonucleotides (ASO) or small interfering ribonucleic acids that target RNA transcripts are achieving spectacular success in treating these diseases. For Duchenne muscular dystrophy (DMD), the state-of-the-art is an exon skipping therapy using an antisense oligonucleotide, which is prototypical of advanced precision medicines. Very recently, golodirsen and viltolarsen, for treatment of DMD patients amenable to skipping exon 53, have been approved by regulatory agencies in the USA and Japan, respectively. Here, we review scientific and clinical progress in developing new oligonucleotide therapeutics for selected rare neuromuscular diseases, discussing their efficacy and limitations.

scholarly journals International Cooperation as a Prerequisite for Improvement of Access to Orphan Biologic Medicines

2021 ◽  
Vol 14 (2) ◽  
Author(s):  
Zbigniew Więckowski
Keyword(s):  
International Cooperation ◽  
Rare Diseases ◽  
Patent Protection ◽  
Positive Impact ◽  
Mutual Recognition ◽  
Orphan Drugs ◽  
Economic Incentives ◽  
Regulatory Agencies ◽  
The Usa ◽  
The Eu

Rare diseases constitute a global problem. Worldwide, 350 million people suffer from such diseases. The number of diagnosed cases are on the rise. Only a small percentage of those suffering have the opportunity to be treated with modern therapies. Medicines used to treat rare diseases are called orphan drugs. Biologic medicines developed for orphan drug indications, besides patent protection, have a period of regulatory and market exclusivity. After this period of time has elapsed, access to orphan drugs could be improved by the introduction of biosimilar medicines. The biggest challenge is to develop effective legal, tax and economic incentives to stimulate the development of biosimilar medicines for orphan indications. The regulatory agencies - EMA in the EU and the FDA in the USA - play a key role in increasing access to orphan biologics. Undoubtedly, the international cooperation, especially the mutual recognition of registration procedures between countries, and the creation of a common vocabulary and the unification of incentives for the pharmaceutical industry would have the positive impact on access to modern therapies.

Effect of new dietary supplement on sperm quality

2012 ◽  
Vol 153 (45) ◽  
pp. 1787-1792 ◽  
Author(s):  
Mária Horváth ◽  
Endre Czeizel
Keyword(s):  
Adverse Effect ◽  
Clinical Trial ◽  
Dietary Supplement ◽  
Male Fertility ◽  
Sperm Quality ◽  
Sperm Count ◽  
Before And After ◽  
The Usa ◽  
New Treatments

Introduction: There is a decline in male fertility thus new treatments are needed. Aims: To test the efficacy of a new dietary supplement developed in the USA and registered as a curing drug in Hungary (OGYI). Methods: In a clinical trial 100 men with low sperm quality (spermium count 5–20 M/ml, good motility 10–40%, and adverse shape 30–50%) were examined. Results: Sperm parameters were measured before and after a 3-month treatment and after another 3-month without treatment. This dietary supplement statistically and clinically significantly improved sperm count and motility. In 74 cases this dietary supplement demonstrated a beneficial effect on sperm quality (more than 10% increase in sperm count, or quality of motility, or shape); in 16 cases the improvement exceeded 30%. No adverse effect could be accounted for this treatment. Conclusions: This new dietary supplement may contribute to the treatment of male infertility. Orv. Hetil., 2012, 153, 1787–1792.

Boilerplate

2012 ◽  
Author(s):  
Margaret Jane Radin
Keyword(s):  
Economic Efficiency ◽  
Analytical Framework ◽  
Daily Basis ◽  
Regulatory Agencies ◽  
Jury Trial ◽  
Comprehensive Treatment ◽  
New Methods ◽  
And Control ◽  
Fine Print

Boilerplate—the fine-print terms and conditions that we become subject to when we click “I agree” online, rent an apartment, or enter an employment contract, for example—pervades all aspects of our modern lives. On a daily basis, most of us accept boilerplate provisions without realizing that should a dispute arise about a purchased good or service, the nonnegotiable boilerplate terms can deprive us of our right to jury trial and relieve providers of responsibility for harm. Boilerplate is the first comprehensive treatment of the problems posed by the increasing use of these terms, demonstrating how their use has degraded traditional notions of consent, agreement, and contract, and sacrificed core rights whose loss threatens the democratic order. This book examines attempts to justify the use of boilerplate provisions by claiming either that recipients freely consent to them or that economic efficiency demands them, and it finds these justifications wanting. It argues that our courts, legislatures, and regulatory agencies have fallen short in their evaluation and oversight of the use of boilerplate clauses. To improve legal evaluation of boilerplate, the book offers a new analytical framework, one that takes into account the nature of the rights affected, the quality of the recipient's consent, and the extent of the use of these terms. It goes on to offer possibilities for new methods of boilerplate evaluation and control, and concludes by discussing positive steps that NGOs, legislators, regulators, courts, and scholars could take to bring about better practices.

Trial by Triad: substituted judgment, mental illness and the right to die

2021 ◽  
pp. medethics-2020-107154
Author(s):  
Jacob M Appel
Keyword(s):  
Depressive Symptoms ◽  
Depressive Disorders ◽  
Substituted Judgment ◽  
Diminished Capacity ◽  
Accepted Standard ◽  
The Usa ◽  
Aid In Dying ◽  
Incapacitated Patients ◽  
The Right

Substituted judgment has increasingly become the accepted standard for rendering decisions for incapacitated adults in the USA. A broad exception exists with regard to patients with diminished capacity secondary to depressive disorders, as such patients’ previous wishes are generally not honoured when seeking to turn down life-preserving care or pursue aid-in-dying. The result is that physicians often force involuntary treatment on patients with poor medical prognoses and/or low quality of life (PMP/LQL) as a result of their depressive symptoms when similarly situated incapacitated patients without such depressive symptoms would have their previous wishes honoured via substituted judgment. This commentary argues for reconsidering this approach and for using a substituted judgment standard for a subset of EMP/LQL patients seeking death.

scholarly journals Comprehensive Overview of Sleep Disorders in Patients with Chronic Liver Disease

2021 ◽  
Vol 11 (2) ◽  
pp. 142
Author(s):  
Oana-Mihaela Plotogea ◽  
Madalina Ilie ◽  
Simona Bungau ◽  
Alexandru Laurentiu Chiotoroiu ◽  
Ana Maria Alexandra Stanescu ◽  
...  
Keyword(s):  
Sleep Disorders ◽  
Daily Practice ◽  
Chronic Liver ◽  
Asian Countries ◽  
Chronic Liver Diseases ◽  
Comprehensive Overview ◽  
The Usa ◽  
The Impact ◽  
Reliable Methods

The impact of sleep disorders (SDs) on patients with chronic liver diseases (CLD) is tremendous. SDs are frequently encountered among these patients and interfere with their quality of life. This review aims to present the data available so far about the prevalence, phenotypes, and proposed pathophysiological mechanisms of SDs in CLD. Moreover, we proposed to search the literature regarding the most reliable methods to assess SDs and the possible therapeutic options in patients with CLD. The main results of this review show that when it comes to prevalence, the percentages reported vary widely between studies performed among populations from the USA or Europe and those coming from Asian countries. Furthermore, it has been proven that SDs may also be present in the absence of neurocognitive disorders attributable to hepatic encephalopathy (HE), which contradicts traditional suppositions where SDs were considered part of the clinical scenario of HE. Currently, there are no specific recommendations or protocols to assess SDs in CLD patients and data about the therapeutic management are limited. Taking into consideration their impact, a protocol for diagnosing and managing SDs should be developed and included in the daily practice of hepatologists.

scholarly journals Influence of Bagging on the Development and Quality of Fruits

Plants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 358
Author(s):  
Muhammad Moaaz Ali ◽  
Raheel Anwar ◽  
Ahmed F. Yousef ◽  
Binqi Li ◽  
Andrea Luvisi ◽  
...  
Keyword(s):  
Fruit Quality ◽  
Consumer Choice ◽  
Abiotic Factors ◽  
Market Value ◽  
Quality Attribute ◽  
Export Markets ◽  
External Appearance ◽  
The Usa ◽  
Main Determinants

Fruit quality is certainly influenced by biotic and abiotic factors, and a main quality attribute is the external appearance of the fruit. Various possible agronomical approaches are able to regulate the fruit microenvironment and, consequently, improve fruit quality and market value. Among these, fruit bagging has recently become an integral part of fruits’ domestic and export markets in countries such as Japan, China, Korea Australia and the USA because it is a safe and eco-friendly technique to protect fruits from multiple stresses, preserving or improving the overall quality. Despite increasing global importance, the development of suitable bagging materials and, above all, their use in the field is quite laborious, so that serious efforts are required to enhance and standardize bagging material according to the need of the crops/fruits. This review provides information about the effects of bagging technique on the fruit aspect and texture, which are the main determinants of consumer choice.

scholarly journals Nutraceutical Screening in a Zebrafish Model of Muscular Dystrophy: Gingerol as a Possible Food Aid

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 998
Author(s):  
Rosario Licitra ◽  
Maria Marchese ◽  
Letizia Brogi ◽  
Baldassare Fronte ◽  
Letizia Pitto ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Muscular Dystrophy ◽  
Genomic Medicine ◽  
Neuromuscular Diseases ◽  
Dystrophin Gene ◽  
Neuromuscular Disorder ◽  
Heme Oxygenase 1 ◽  
Zebrafish Model ◽  
Screening Study

Duchenne muscular dystrophy (DMD), caused by mutations in the dystrophin gene, is an inherited neuromuscular disorder that causes loss of muscle mass and motor skills. In the era of genomic medicine, there is still no known cure for DMD. In clinical practice, there is a growing awareness of the possible importance of nutrition in neuromuscular diseases. This is mostly the result of patients’ or caregivers’ empirical reports of how active substances derived from food have led to improved muscle strength and, thus, better quality of life. In this report, we investigate several nutraceutical principles in the sapje strain of zebrafish, a validated model of DMD, in order to identify possible natural products that, if supplemented in the diet, might improve the quality of life of DMD patients. Gingerol, a constituent of fresh ginger, statistically increased the locomotion of mutant larvae and upregulated the expression of heme oxygenase 1, a target gene for therapy aimed at improving dystrophic symptoms. Although three other compounds showed a partial positive effect on locomotor and muscle structure phenotypes, our nutraceutical screening study lent preliminary support to the efficacy and safety only of gingerol. Gingerol could easily be proposed as a dietary supplement in DMD.

scholarly journals Polypurine Reverse-Hoogsteen Hairpins as a Tool for Exon Skipping at the Genomic Level in Mammalian Cells

2021 ◽  
Vol 22 (7) ◽  
pp. 3784
Author(s):  
Véronique Noé ◽  
Carlos J. Ciudad
Keyword(s):  
Dna Sequencing ◽  
Rare Diseases ◽  
Mammalian Cells ◽  
Mrna Level ◽  
Exon Skipping ◽  
Selective Medium ◽  
Rt Pcr ◽  
Exon 2 ◽  
Reading Frame ◽  
Additional Exon

Therapeutic strategies for rare diseases based on exon skipping are aimed at mediating the elimination of mutated exons and restoring the reading frame of the affected protein. We explored the capability of polypurine reverse-Hoogsteen hairpins (PPRHs) to cause exon skipping in NB6 cells carrying a duplication of exon 2 of the DHFR gene that causes a frameshift abolishing DHFR activity. Methods: Different editing PPRHs were designed and transfected in NB6 cells followed by incubation in a DHFR-selective medium lacking hypoxanthine and thymidine. Surviving colonies were analyzed by DNA sequencing, RT-PCR, Western blotting and DHFR enzymatic activity. Results: Transfection of editing PPRHs originated colonies in the DHFR-selective medium. DNA sequencing results proved that the DHFR sequence in all these colonies corresponded to the wildtype sequence with just one copy of exon 2. In the edited colonies, the skipping of the additional exon was confirmed at the mRNA level, the DHFR protein was restored, and it showed high levels of DHFR activity. Conclusions: Editing-PPRHs are able to cause exon skipping at the DNA level and could be applied as a possible therapeutic tool for rare diseases.

scholarly journals Bioinsecticides based on plant essential oils: a short overview

2020 ◽  
Vol 75 (7-8) ◽  
pp. 179-182
Author(s):  
Murray B. Isman
Keyword(s):  
Essential Oils ◽  
Crop Protection ◽  
Large Body ◽  
Regulatory Agencies ◽  
The European Union ◽  
Plant Essential Oils ◽  
The Past ◽  
Wide Range ◽  
The Usa ◽  
Regulatory Challenges

AbstractInterest in the discovery and development of plant essential oils for use as bioinsecticides has grown enormously in the past 20 years. However, successful commercialization and utilization of crop protection products based on essential oils has thus far lagged far behind their promise based on this large body of research, most notably because with the exceptions of the USA and Australia, such products receive no special status from regulatory agencies that approve new pesticides for use. Essential oil-based insecticides have now been used in the USA for well over a decade, and more recently have seen use in the European Union (EU), Korea, and about a dozen other countries, with demonstrated efficacy against a wide range of pests and in numerous crop systems. For the most part these products are based on commodity essential oils developed as flavor and fragrance agents for the food and cosmetic industries, as there are formidable logistic, economic, and regulatory challenges to the use of many other essential oils that otherwise possess potentially useful bioactivity against pests. In spite of these limitations, the overall prospects for biopesticides, including those based on essential oils, are encouraging as the demand for sustainably-produced and/or organic food continues to increase worldwide.

Eagle Syndrome: an underdiagnosed cause of orofacial pain

2021 ◽  
Vol 14 (1) ◽  
pp. e238161
Author(s):  
João Ferreira de Barros ◽  
Maria Vieira Rodrigues ◽  
Leonor Aurélio Barroso ◽  
Isabel Cruz Amado
Keyword(s):  
Orofacial Pain ◽  
Rare Condition ◽  
Styloid Process ◽  
High Clinical Suspicion ◽  
Body Sensation ◽  
Cervical Approach ◽  
Considerable Length ◽  
Eagle Syndrome

Eagle Syndrome (ES), also termed stylohyoid syndrome or styloid syndrome, is a rare condition characterised by a cluster of symptoms related to an elongation of the styloid process (SP) of the temporal bone. These may range from mild pharyngeal foreign body sensation and dysphagia to severe orofacial pain. High clinical suspicion is necessary owing to the unspecific clinical picture and limited diagnostic clues. Until a definitive diagnosis is achieved, these patients may develop symptoms which significantly impact their quality of life. The aim of this article is to report a case of ES in which a considerable length of SP was documented. Diagnosis was made years after the initial complaints and several medical workups by different specialties. Surgical resection of the elongated process by cervical approach was the adopted treatment modality. Patient recovery and follow-up was satisfactory, with remission of the afflicting symptoms.

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