Previous Issue

Table of Contents

J. Pers. Med., Volume 9, Issue 1 (March 2019)

  • Issues are regarded as officially published after their release is announced to the table of contents alert mailing list.
  • You may sign up for e-mail alerts to receive table of contents of newly released issues.
  • PDF is the official format for papers published in both, html and pdf forms. To view the papers in pdf format, click on the "PDF Full-text" link, and use the free Adobe Readerexternal link to open them.
View options order results:
result details:
Displaying articles 1-14
Export citation of selected articles as:
Open AccessReview Autonomy Challenges in Epigenetic Risk-Stratified Cancer Screening: How Can Patient Decision Aids Support Informed Consent?
J. Pers. Med. 2019, 9(1), 14; https://doi.org/10.3390/jpm9010014
Received: 11 February 2019 / Accepted: 14 February 2019 / Published: 18 February 2019
Viewed by 193 | PDF Full-text (622 KB)
Abstract
Information of an individual's epigenome can be useful in cancer screening to enable personalised decision making on participation, treatment options and further screening strategies. However, adding this information might result in complex risk predictions on multiple diseases, unsolicited findings and information on (past) [...] Read more.
Information of an individual's epigenome can be useful in cancer screening to enable personalised decision making on participation, treatment options and further screening strategies. However, adding this information might result in complex risk predictions on multiple diseases, unsolicited findings and information on (past) environmental exposure and behaviour. This complicates informed consent procedures and may impede autonomous decision-making. In this article we investigate and identify the specific features of epigenetic risk-stratified cancer screening that challenge the current informed consent doctrine. Subsequently we describe current and new informed consent models and the principle of respect for autonomy and argue for a specific informed consent model for epigenetic risk-stratified screening programmes. Next, we propose a framework that guides the development of Patient Decision Aids (PDAs) to support informed consent and promote autonomous choices in the specific context of epigenetic cancer screening programmes. Full article
(This article belongs to the Special Issue Risk-stratified Cancer Screening)
Open AccessArticle The Association between Plasma Omega-6/Omega-3 Ratio and Anthropometric Traits Differs by Racial/Ethnic Groups and NFKB1 Genotypes in Healthy Young Adults
J. Pers. Med. 2019, 9(1), 13; https://doi.org/10.3390/jpm9010013
Received: 17 January 2019 / Revised: 12 February 2019 / Accepted: 13 February 2019 / Published: 16 February 2019
Viewed by 194 | PDF Full-text (755 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and [...] Read more.
Evidence for a relationship between omega-6/omega-3 (n-6/n-3) polyunsaturated fatty acid (PUFA) ratio and obesity in humans is inconsistent, perhaps due to differences in dietary intake or metabolism of PUFAs between different subsets of the population. Since chronic inflammation is central to obesity and inflammatory pathways are regulated by PUFAs, the objective of this study was to examine whether variants in the NFKB1 gene, an upstream regulator of the inflammatory response, modify the association between the n-6/n-3 ratio (from diet and plasma) and anthropometric traits in a multiethnic/multiracial population of young adults. Participants’ (n = 898) dietary PUFA intake was assessed using a food frequency questionnaire and plasma PUFA concentrations by gas chromatography. Nine tag single nucleotide polymorphisms (SNP) in NFKB1 were genotyped. Significant interactions were found between racial/ethnic groups and plasma n-6/n-3 ratio for body mass index (BMI) (p = 0.02) and waist circumference (WC) (p = 0.007). Significant interactions were also observed between racial/ethnic groups and three NFKB1 genotypes (rs11722146, rs1609798, and rs230511) for BMI and WC (all p ≤ 0.04). Significant interactions were found between two NFKB1 genotypes and plasma n-6/n-3 ratio for BMI and WC (rs4648090 p = 0.02 and 0.03; rs4648022 p = 0.06 and 0.04, respectively). Our findings suggest that anthropometric traits may be influenced by a unique combination of n-6/n-3 ratio, racial/ethnic background, and NFKB1 genotypes. Full article
(This article belongs to the Special Issue Nutrigenomics)
Figures

Figure 1

Open AccessReview The Developing Story of Predictive Biomarkers in Colorectal Cancer
J. Pers. Med. 2019, 9(1), 12; https://doi.org/10.3390/jpm9010012
Received: 24 November 2018 / Revised: 28 January 2019 / Accepted: 4 February 2019 / Published: 7 February 2019
Viewed by 573 | PDF Full-text (478 KB)
Abstract
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the [...] Read more.
Colorectal cancer (CRC) is the third most common malignancy worldwide. Surgery remains the most important treatment for non-metastatic CRC, and the administration of adjuvant chemotherapy depends mainly on the disease stage, which is still the strongest prognostic factor. A refined understanding of the genomics of CRC has recently been achieved thanks to the widespread use of next generation sequencing with potential future therapeutic implications. Microsatellite instability (MSI) has been suggested as a predictive marker for response to anti-programmed-cell-death protein 1 (PD-1) therapy in solid tumors, including CRC. It should be noted that not all cancers with MSI phenotype respond to anti-PD-1 immunotherapy, highlighting the urgent need for even better predictive biomarkers. Mitogen-Activated Protein Kinase (MAPK) pathway genes KRAS, NRAS, and BRAF represent important molecular targets and could serve as independent prognostic biomarkers in CRC, and identify those who potentially benefit from anti-epidermal growth factor receptor (EGFR) treatment. Emerging evidence has attributed a significant role to inflammatory markers including blood cell ratios in the prognosis and survival of CRC patients; these biomarkers can be easily assessed in routine blood exams and be used to identify high-risk patients or those more likely to benefit from chemotherapy, targeted therapies and potentially immunotherapy. Analysis of cell-free DNA (cfDNA), circulating tumor cells (CTC) and/or micro RNAs (miRNAs) could provide useful information for the early diagnosis of CRC, the identification of minimal residual disease and, the evaluation of the risk of recurrence in early CRC patients. Even the selection of patients suitable for the new targeted therapy is becoming possible with the use of predictive miRNA biomarkers. Finally, the development of treatment resistance with the emergence of chemo-resistance clones after treatment remains the most important challenge in the clinical practice. In this context it is crucial to identify potential biomarkers and therapeutic targets which could lead to development of new and more effective treatments. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
Open AccessArticle The Interaction between Genetic Polymorphisms in FTO and TCF7L2 Genes and Dietary Intake with Regard to Body Mass and Composition: An Exploratory Study
J. Pers. Med. 2019, 9(1), 11; https://doi.org/10.3390/jpm9010011
Received: 12 November 2018 / Revised: 10 January 2019 / Accepted: 18 January 2019 / Published: 5 February 2019
Viewed by 405 | PDF Full-text (476 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
In contrast to the large number of genetic studies on obesity, there has been significantly less nutrigenetics investigation of the interaction between diet and single nucleotide polymorphisms (SNPs) in obesity, especially within Eastern Mediterranean populations. The aim of this study was to evaluate [...] Read more.
In contrast to the large number of genetic studies on obesity, there has been significantly less nutrigenetics investigation of the interaction between diet and single nucleotide polymorphisms (SNPs) in obesity, especially within Eastern Mediterranean populations. The aim of this study was to evaluate the potential interactions between three candidate SNPs, namely, rs1558902 and rs9939609 in the fat mass and obesity (FTO) gene and the rs7903146 variant of the Transcription factor 7 like 2 (TCF7L2) gene, and macronutrient intake with regard to obesity, body fat, and muscle composition. Three hundred and eight healthy Lebanese adults were included in this study. Data collection included a questionnaire for demographics and lifestyle in addition to a detailed dietary assessment using a culture-specific 80-item semi-quantitative food frequency questionnaire. This was coupled with anthropometric measurements and peripheral blood withdrawal for DNA and genotyping using Taqman allele discrimination assays. The two FTO candidate SNPs were not associated with risk of obesity in this population sample, yet there was a trend, though not a significant one, towards lower muscle mass among carriers of the risk allele of either FTO SNPs. To our knowledge, these results have not been previously reported. As for the TCF7L2 rs7903146 variant, results were congruent with the literature, given that individuals who were homozygous for the risk allele had significantly higher body mass index (BMI) and body fat despite lower intakes of saturated fat. Similar interactions, though not significant, were shown with muscle mass, whereby individuals who were homozygous for the risk allele had lower muscle mass with higher intakes of saturated fat, a result that, to our knowledge, has not been previously reported. Full article
(This article belongs to the Special Issue Nutrigenomics)
Figures

Figure 1

Open AccessCommentary Understanding Implementation Challenges to Genetic Testing for Familial Hypercholesterolemia in the United States
J. Pers. Med. 2019, 9(1), 9; https://doi.org/10.3390/jpm9010009
Received: 2 January 2019 / Revised: 19 January 2019 / Accepted: 21 January 2019 / Published: 1 February 2019
Viewed by 350 | PDF Full-text (201 KB) | HTML Full-text | XML Full-text
Abstract
Cardiovascular disease (CVD) is the leading cause of death in the United States (US), with familial hypercholesterolemia (FH) being a major inherited and genetic risk factor for premature CVD and atherosclerosis. Genetic testing has helped patients and providers confirm the presence of known [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death in the United States (US), with familial hypercholesterolemia (FH) being a major inherited and genetic risk factor for premature CVD and atherosclerosis. Genetic testing has helped patients and providers confirm the presence of known pathogenic and likely pathogenic variations in FH-associated genes. Key organizations, such as the Centers for Disease Control and Prevention (CDC), American Heart Association (AHA), FH Foundation, and National Lipid Association (NLA), have recognized the clinical utility of FH genetic testing. However, FH genetic testing is underutilized in clinical practice in the US for reasons that are underexplored through the lens of implementation science. In this commentary, we discuss seven key implementation challenges that must be overcome to strengthen the clinical adoption of FH genetic testing in the US. These implementation challenges center on evidence of cost-effectiveness, navigating patient and provider preferences and concerns, gender and ethnic diversity and representation in genetic testing, and establishing clinical consensus around FH genetic testing based on the latest and most relevant research findings. Overcoming these implementation challenges is imperative to the mission of reducing CVD risk in the US. Full article
(This article belongs to the Special Issue Genomic Medicine and Policy)
Open AccessArticle VARIFI—Web-Based Automatic Variant Identification, Filtering and Annotation of Amplicon Sequencing Data
J. Pers. Med. 2019, 9(1), 10; https://doi.org/10.3390/jpm9010010
Received: 28 December 2018 / Revised: 26 January 2019 / Accepted: 28 January 2019 / Published: 1 February 2019
Viewed by 334 | PDF Full-text (1178 KB)
Abstract
Fast and affordable benchtop sequencers are becoming more important in improving personalized medical treatment. Still, distinguishing genetic variants between healthy and diseased individuals from sequencing errors remains a challenge. Here we present VARIFI, a pipeline for finding reliable genetic variants (single nucleotide polymorphisms [...] Read more.
Fast and affordable benchtop sequencers are becoming more important in improving personalized medical treatment. Still, distinguishing genetic variants between healthy and diseased individuals from sequencing errors remains a challenge. Here we present VARIFI, a pipeline for finding reliable genetic variants (single nucleotide polymorphisms (SNPs) and insertions and deletions (indels)). We optimized parameters in VARIFI by analyzing more than 170 amplicon-sequenced cancer samples produced on the Personal Genome Machine (PGM). In contrast to existing pipelines, VARIFI combines different analysis methods and, based on their concordance, assigns a confidence score to each identified variant. Furthermore, VARIFI applies variant filters for biases associated with the sequencing technologies (e.g., incorrectly identified homopolymer-associated indels with Ion Torrent). VARIFI automatically extracts variant information from publicly available databases and incorporates methods for variant effect prediction. VARIFI requires little computational experience and no in-house compute power since the analyses are conducted on our server. VARIFI is a web-based tool available at varifi.cibiv.univie.ac.at. Full article
Open AccessReview Personalized Assessment of the Coronary Atherosclerotic Arteries by Intravascular Ultrasound Imaging: Hunting the Vulnerable Plaque
J. Pers. Med. 2019, 9(1), 8; https://doi.org/10.3390/jpm9010008
Received: 25 November 2018 / Revised: 3 January 2019 / Accepted: 21 January 2019 / Published: 24 January 2019
Viewed by 412 | PDF Full-text (956 KB) | HTML Full-text | XML Full-text
Abstract
The term “vulnerable plaque” is commonly used to refer to an atherosclerotic plaque that is prone to rupture and the formation of thrombosis, which can lead to several cardiovascular and cerebrovascular events. Coronary artery atherosclerosis has a wide variety of different phenotypes among [...] Read more.
The term “vulnerable plaque” is commonly used to refer to an atherosclerotic plaque that is prone to rupture and the formation of thrombosis, which can lead to several cardiovascular and cerebrovascular events. Coronary artery atherosclerosis has a wide variety of different phenotypes among patients who may have a substantially variable risk for plaque rupture and cardiovascular events. Mounting evidence has proposed three distinctive histopathological mechanisms: plaque rupture, plaque erosion and calcified nodules. Studies have demonstrated the characteristics of plaques with high vulnerability such as the presence of a thin fibrous cap, a necrotic lipid-rich core, abundant infiltrating macrophages and neovascularization. However, traditional coronary angiographic imaging fails to determine plaque vulnerability features, and its ability to individualize treatment strategies is limited. In recent decades, catheter-based intravascular ultrasound imaging (IVUS) modalities have been developed to identify vulnerable plaques and ultimately vulnerable patients. The aim is to individualize prediction, prevention and treatment of acute coronary events based on the identification of specific features of high-risk atherosclerotic plaques, and to identify the most appropriate interventional procedures for their treatment. In this context, the aim of this review is to discuss how personalized assessment of coronary atherosclerotic arteries can be achieved by intravascular ultrasound imaging focusing on vulnerable plaque detection. Full article
(This article belongs to the Special Issue Personalized and Targeted Atherosclerosis Treatments)
Figures

Figure 1

Open AccessReview Pharmacogenomics of Novel Direct Oral Anticoagulants: Newly Identified Genes and Genetic Variants
J. Pers. Med. 2019, 9(1), 7; https://doi.org/10.3390/jpm9010007
Received: 29 October 2018 / Revised: 24 December 2018 / Accepted: 11 January 2019 / Published: 17 January 2019
Viewed by 617 | PDF Full-text (1117 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a [...] Read more.
Direct oral anticoagulants (DOAC) have shown an upward prescribing trend in recent years due to favorable pharmacokinetics and pharmacodynamics without requirement for routine coagulation monitoring. However, recent studies have documented inter-individual variability in plasma drug levels of DOACs. Pharmacogenomics of DOACs is a relatively new area of research. There is a need to understand the role of pharmacogenomics in the interpatient variability of the four most commonly prescribed DOACs, namely dabigatran, rivaroxaban, apixaban, and edoxaban. We performed an extensive search of recently published research articles including clinical trials and in-vitro studies in PubMed, particularly those focusing on genetic loci, single nucleotide polymorphisms (SNPs), and DNA polymorphisms, and their effect on inter-individual variation of DOACs. Additionally, we also focused on commonly associated drug-drug interactions of DOACs. CES1 and ABCB1 SNPs are the most common documented genetic variants that contribute to alteration in peak and trough levels of dabigatran with demonstrated clinical impact. ABCB1 SNPs are implicated in alteration of plasma drug levels of rivaroxaban and apixaban. Studies conducted with factor Xa, ABCB1, SLCOB1, CYP2C9, and VKORC1 genetic variants did not reveal any significant association with plasma drug levels of edoxaban. Pharmacokinetic drug-drug interactions of dabigatran are mainly mediated by p-glycoprotein. Strong inhibitors and inducers of CYP3A4 and p-glycoprotein should be avoided in patients treated with rivaroxaban, apixaban, and edoxaban. We conclude that some of the inter-individual variability of DOACs can be attributed to alteration of genetic variants of gene loci and drug-drug interactions. Future research should be focused on exploring new genetic variants, their effect, and molecular mechanisms that contribute to alteration of plasma levels of DOACs. Full article
Figures

Figure 1

Open AccessEditorial Acknowledgement to Reviewers of JPM in 2018
J. Pers. Med. 2019, 9(1), 6; https://doi.org/10.3390/jpm9010006
Published: 17 January 2019
Viewed by 351 | PDF Full-text (113 KB) | HTML Full-text | XML Full-text
Abstract
Rigorous peer-review is the corner-stone of high-quality academic publishing [...] Full article
Open AccessReview The Emerging Role of Checkpoint Inhibition in Microsatellite Stable Colorectal Cancer
J. Pers. Med. 2019, 9(1), 5; https://doi.org/10.3390/jpm9010005
Received: 30 November 2018 / Revised: 5 January 2019 / Accepted: 11 January 2019 / Published: 16 January 2019
Viewed by 572 | PDF Full-text (810 KB) | HTML Full-text | XML Full-text
Abstract
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit [...] Read more.
Checkpoint inhibitor therapy has introduced a revolution in contemporary anticancer therapy. It has led to dramatic improvements in patient outcomes and has spawned tremendous research into novel immunomodulatory agents and combination therapy that has changed the trajectory of cancer care. However, clinical benefit in patients with colorectal cancer has been generally limited to tumors with loss of mismatch repair function and those with specific germline mutations in the DNA polymerase gene. Unfortunately, tumors with these specific mutator phenotypes are in the minority. Recent pre-clinical and clinical studies have begun to reveal encouraging results suggesting that checkpoint inhibitor therapy can be expanded to an increasing number of colorectal tumors with microsatellite stability and the absence of traditional predictive biomarkers of checkpoint inhibitor response. These studies generally rely on combinations of checkpoint inhibitors with chemotherapy, molecular targeted therapy, radiation therapy, or other novel immunomodulatory agents. This article will review the most current data in microsatellite stable colorectal cancer. Full article
(This article belongs to the Special Issue Biomarkers in Colorectal Cancer)
Figures

Figure 1

Open AccessReview Re-Examining Genetic Screening and Oral Contraceptives: A Patient-Centered Review
J. Pers. Med. 2019, 9(1), 4; https://doi.org/10.3390/jpm9010004
Received: 10 November 2018 / Revised: 9 January 2019 / Accepted: 11 January 2019 / Published: 15 January 2019
Viewed by 420 | PDF Full-text (250 KB) | HTML Full-text | XML Full-text
Abstract
The World Health Organization classifies combined hormonal contraception as an unacceptable health risk in the presence of a known thrombogenic mutation but advises against routine thrombophilia screening before initiating combined oral contraceptives (COCs) on the grounds of high screening costs and low prevalence. [...] Read more.
The World Health Organization classifies combined hormonal contraception as an unacceptable health risk in the presence of a known thrombogenic mutation but advises against routine thrombophilia screening before initiating combined oral contraceptives (COCs) on the grounds of high screening costs and low prevalence. From the perspective of patient-centered care, we examine cost, prevalence, and other published arguments for and against thrombophilia screening before initiating COCs. Our patient-centered review draws on relevant empirical evidence concerning the advantages and disadvantages of thrombophilia screening, while placing the discussion in the broader context of evolving attitudes toward genetic testing and a shifting policy landscape that provides many women direct access to COCs and/or thrombophilia screening. Given variation in prior probabilities of thrombophilia, expected exposure to other risk factors for venous thromboembolism, attitudes towards risk, expected reactions to a positive test result, ability to pay, and concerns about genetic discrimination, we conclude that the current one-size-fits-most approach is not consistent with patient-centered care. Instead, we advocate for greater patient and provider education concerning the implications of thrombophilia screening. Moreover, we recommend offering patients optional thrombophilia screening before initiating COCs. Full article
Open AccessReview Colorectal Cancer Biomarkers in the Era of Personalized Medicine
J. Pers. Med. 2019, 9(1), 3; https://doi.org/10.3390/jpm9010003
Received: 3 December 2018 / Revised: 10 January 2019 / Accepted: 10 January 2019 / Published: 14 January 2019
Viewed by 589 | PDF Full-text (261 KB) | HTML Full-text | XML Full-text
Abstract
The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears [...] Read more.
The 5-year survival probability for patients with metastatic colorectal cancer has not drastically changed over the last several years, nor has the backbone chemotherapy in first-line disease. Nevertheless, newer targeted therapies and immunotherapies have been approved primarily in the refractory setting, which appears to benefit a small proportion of patients. Until recently, rat sarcoma (RAS) mutations remained the only genomic biomarker to assist with therapy selection in metastatic colorectal cancer. Next generation sequencing has unveiled many more potentially powerful predictive genomic markers of therapy response. Importantly, there are also clinical and physiologic predictive or prognostic biomarkers, such as tumor sidedness. Variations in germline pharmacogenomic biomarkers have demonstrated usefulness in determining response or risk of toxicity, which can be critical in defining dose intensity. This review outlines such biomarkers and summarizes their clinical implications on the treatment of colorectal cancer. It is critical that clinicians understand which biomarkers are clinically validated for use in practice and how to act on such test results. Full article
Open AccessArticle Association of TLR4 Polymorphisms, Expression, and Vitamin D with Helicobacter pylori Infection
J. Pers. Med. 2019, 9(1), 2; https://doi.org/10.3390/jpm9010002
Received: 15 November 2018 / Revised: 21 December 2018 / Accepted: 3 January 2019 / Published: 11 January 2019
Viewed by 496 | PDF Full-text (433 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Helicobacter pylori (H. pylori) infection is the strongest recognized risk factor for gastric adenocarcinoma. Since previous observations have shown that polymorphisms in innate immune system genes, as well as vitamin D (VitD) levels, could modify the risk of infection with Helicobacter [...] Read more.
Helicobacter pylori (H. pylori) infection is the strongest recognized risk factor for gastric adenocarcinoma. Since previous observations have shown that polymorphisms in innate immune system genes, as well as vitamin D (VitD) levels, could modify the risk of infection with Helicobacter pylori (H. pylori), we analyzed the relation between single nucleotide polymorphisms (SNPs) in TLRs (TLR1, TLR2, TLR4) CD14, RUNX3 and VitD levels with H. pylori infection. A case-control study on four hundred sixty Lebanese individuals was conducted. Eleven SNPs in total were genotyped and gene expression analysis using real-time PCR was performed in white blood cells of a subsample of eight individuals. A total of 49% of the participants were affected. Although no direct association was found between the SNPs and H. pylori infection, rs4986790G>A and rs4986791T>C in TLR4 were negatively associated with VitD levels (β = −0.371, p = 5 × 10−3 and β = −0.4, p = 2 × 10−3, respectively), which was negatively associated with H. pylori infection (OR = 0.01, p < 1 × 10−3). TLR4 expression was 3× lower in individuals with H. pylori compared with non-infected (p = 0.01). TLR4 polymorphisms, expression, and VitD could be implicated in H. pylori infection and further development of gastric adenocarcinoma. Full article
Figures

Figure 1

Open AccessReview Restoring Dystrophin Expression in Duchenne Muscular Dystrophy: Current Status of Therapeutic Approaches
J. Pers. Med. 2019, 9(1), 1; https://doi.org/10.3390/jpm9010001
Received: 8 December 2018 / Revised: 30 December 2018 / Accepted: 1 January 2019 / Published: 7 January 2019
Viewed by 1327 | PDF Full-text (247 KB) | HTML Full-text | XML Full-text
Abstract
Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by progressive muscle weakness, is caused by the absence or a decreased amount of the muscle cytoskeletal protein dystrophin. Currently, several therapeutic approaches to cure DMD are being investigated, which can be categorized into [...] Read more.
Duchenne muscular dystrophy (DMD), a rare genetic disorder characterized by progressive muscle weakness, is caused by the absence or a decreased amount of the muscle cytoskeletal protein dystrophin. Currently, several therapeutic approaches to cure DMD are being investigated, which can be categorized into two groups: therapies that aim to restore dystrophin expression, and those that aim to compensate for the lack of dystrophin. Therapies that restore dystrophin expression include read-through therapy, exon skipping, vector-mediated gene therapy, and cell therapy. Of these approaches, the most advanced are the read-through and exon skipping therapies. In 2014, ataluren, a drug that can promote ribosomal read-through of mRNA containing a premature stop codon, was conditionally approved in Europe. In 2016, eteplirsen, a morpholino-based chemical capable of skipping exon 51 in premature mRNA, received conditional approval in the USA. Clinical trials on vector-mediated gene therapy carrying micro- and mini- dystrophin are underway. More innovative therapeutic approaches include CRISPR/Cas9-based genome editing and stem cell-based cell therapies. Here we review the current status of therapeutic approaches for DMD, focusing on therapeutic approaches that can restore dystrophin. Full article
J. Pers. Med. EISSN 2075-4426 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top