RESUMEN
BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the brain. Despite existing treatments, there remains an unmet need for therapies that can halt or reverse disease progression. Gene therapy has been tried and tested for a variety of illnesses, including PD. The goal of this systematic review is to assess gene therapy techniques' safety and effectiveness in PD clinical trials. METHODS: Online databases PubMed/Medline, and Cochrane were used to screen the studies for this systematic review. The risk of bias of the included studies was assessed using standard tools. RESULTS: Gene therapy can repair damaged dopaminergic neurons from the illness or deal with circuit anomalies in the basal ganglia connected to Parkinson's disease symptoms. Rather than only treating symptoms, this neuroprotective approach alters the illness itself. Medication for gene therapy is currently administered at the patient's bedside. It can hyperactivate specific brain circuits associated with motor dysfunction. PD therapies are developing quickly, and there aren't enough head-to-head trials evaluating the safety and effectiveness of available treatments. When choosing an advanced therapy, patient-specific factors should be considered in addition to the effectiveness and safety of each treatment option. CONCLUSION: In comparison to conventional therapies, gene therapy may be advantageous for PD. It may minimize side effects, relieve symptoms, and offer dependable dopamine replacement.
Asunto(s)
Terapia Genética , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/terapia , Enfermedad de Parkinson/genética , Terapia Genética/métodos , Resultado del TratamientoRESUMEN
Background: Scleroderma, also referred to as systemic sclerosis, is a multifaceted autoimmune condition characterized by abnormal fibrosis and impaired vascular function. Pathologically, it encompasses the persistent presence of inflammation, abnormal collagen buildup, and restructuring of blood vessels in various organs, resulting in a wide range of clinical symptoms. This review incorporates the most recent scientific literature on scleroderma, with a particular emphasis on its pathophysiology, clinical manifestations, diagnostic approaches, and treatment options. Methodology: A comprehensive investigation was carried out on numerous databases, such as PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar, to collect pertinent studies covering diverse facets of scleroderma research. Results: Scleroderma presents with a range of systemic manifestations, such as interstitial lung disease, gastrointestinal dysmotility, Raynaud's phenomenon, pulmonary arterial hypertension, renal complications, neurological symptoms, and cardiac abnormalities. Serological markers, such as antinuclear antibodies, anti-centromere antibodies, and anti-topoisomerase antibodies, are important for classifying diseases and predicting their outcomes. Discussion: The precise identification of scleroderma is crucial for promptly and correctly implementing effective treatment plans. Treatment approaches aim to improve symptoms, reduce complications, and slow down the progression of the disease. An integrated approach that combines pharmacological agents, including immunosuppressants, endothelin receptor antagonists, and prostanoids, with nonpharmacological interventions such as physical and occupational therapy is essential for maximizing patient care. Conclusion: Through the clarification of existing gaps in knowledge and identification of emerging trends, our goal is to improve the accuracy of diagnosis, enhance the effectiveness of therapeutic interventions, and ultimately enhance the overall quality of life for individuals suffering from scleroderma. Ongoing cooperation and creative research are necessary to advance the field and achieve improved patient outcomes and new therapeutic discoveries.
RESUMEN
Across the globe, cardiovascular disease (CVD) is the leading cause of mortality. According to reports, around 6.2 million people in the United states have heart failure. Current standards of care for heart failure can delay but not prevent progression of disease. Gene therapy is one of the novel treatment modalities that promises to fill this limitation in the current standard of care for Heart Failure. In this paper we performed an extensive search of the literature on various advances made in gene therapy for heart failure till date. We review the delivery methods, targets, current applications, trials, limitations and feasibility of gene therapy for heart failure. Various methods have been employed till date for administering gene therapies including but not limited to arterial and venous infusion, direct myocardial injection and pericardial injection. Various strategies such as AC6 expression, S100A1 protein upregulation, VEGF-B and SDF-1 gene therapy have shown promise in recent preclinical trials. Furthermore, few studies even show that stimulation of cardiomyocyte proliferation such as through cyclin A2 overexpression is a realistic avenue. However, a considerable number of obstacles need to be overcome for gene therapy to be part of standard treatment of care such as definitive choice of gene, gene delivery systems and a suitable method for preclinical trials and clinical trials on patients. Considering the challenges and taking into account the recent advances in gene therapy research, there are encouraging signs to indicate gene therapy for heart failure to be a promising treatment modality for the future. However, the time and feasibility of this option remains in a situation of balance.
Asunto(s)
Enfermedades Cardiovasculares , Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/terapia , Terapia Genética , Técnicas de Transferencia de GenRESUMEN
Dysfunction in the epithelium, breakdown of the blood-brain barrier, and consequent leukocyte and T-cell infiltration into the central nervous system define Vascular Multiple Sclerosis. Multiple sclerosis (MS) affects around 2.5 million individuals worldwide, is the leading cause of neurological impairment in young adults, and can have a variety of progressions and consequences. Despite significant discoveries in immunology and molecular biology, the root cause of MS is still not fully understood, as do the immunological triggers and causative pathways. Recent research into vascular anomalies associated with MS suggests that a vascular component may be pivotal to the etiology of MS, and there can be actually a completely new entity in the already available classification of MS, which can be called 'vascular multiple sclerosis'. Unlike the usual other causes of MS, vascular MS is not dependent on autoimmune pathophysiologic mechanisms, instead, it is caused due to the blood vessels pathology. This review aims to thoroughly analyze existing information and updates about the scattered available findings of genetics, pro-angiogenetic factors, and vascular abnormalities in this important spectrum, the vascular facets of MS.
RESUMEN
Juvenile multiple sclerosis (JMS) is a rare but significant subtype of multiple sclerosis (MS) that affects a small percentage of patients under the age of 10 and 3-5% of all MS patients. Despite its rarity, JMS poses unique challenges in terms of diagnosis, treatment, and management, as it can significantly impact a child or adolescent's physical, cognitive, and emotional development. JMS presents with a varying spectrum of signs and symptoms such as coordination difficulties and permanent cognitive dysfunctions and may include atypical clinical features such as seizures, acute disseminated encephalomyelitis, and optic neuritis, making diagnostic evaluations challenging. Whilst the biology of JMS shares similarities with adult-onset MS, there exist notable distinctions in disease progression, clinical manifestations, and ultimate prognoses. The International Pediatric MS Study Group (IPMSSG) was founded in 2005 to improve understanding of JMS, but there remains a lack of knowledge and guidelines on the management of this condition. This review summarizes the current knowledge on JMS, including its epidemiology, clinical presentations, diagnostic challenges, current treatment options, and outcomes. Current treatment options for JMS include disease-modifying therapies, but JMS can also result in impaired quality of life and psychiatric comorbidity, highlighting the need for comprehensive care for affected children. Through gathering and analyzing scattered studies and recent updates on JMS, the authors aim to address the gaps in current knowledge on JMS and provide an improved understanding of appropriate care for affected children. By doing so, this review hopes to contribute to improving the quality of life and outcomes for JMS patients.
RESUMEN
Multiple sclerosis (MS) is a chronic inflammatory disease that damages the myelin sheath around the axons of the central nervous system. While there are periods of inflammation and remyelination in MS, the latter can sometimes be insufficient and lead to the formation of lesions in the brain and spinal cord. Environmental factors such as vitamin D deficiency, viral or bacterial infections, tobacco smoking, and anxiety have been shown to play a role in the development of MS. Dysbiosis, where the composition of the microbiome changes, may also be involved in the pathogenesis of MS by affecting the gut's microbial population and negatively impacting the integrity of the epithelia. While the cause of MS remains unknown, genetic susceptibility, and immunological dysregulation are believed to play a key role in the development of the disease. Further research is needed to fully understand the complex interplay between genetic, environmental, and microbial factors in the pathogenesis of MS.
RESUMEN
Pancreatic carcinoma (Ca Pancreas) is the third leading cause of cancer-related deaths in the world. The malignancies of the pancreas can be diagnosed with the help of various imaging modalities. An endoscopic ultrasound with a tissue biopsy is so far considered to be the gold standard in terms of the detection of Ca Pancreas, especially for lesions <2 mm. However, other methods, like computed tomography (CT), ultrasound, and magnetic resonance imaging (MRI), are also conventionally used. Moreover, newer techniques, like proteomics, radiomics, metabolomics, and artificial intelligence (AI), are slowly being introduced for diagnosing pancreatic cancer. Regardless, it is still a challenge to diagnose pancreatic carcinoma non-invasively at an early stage due to its delayed presentation. Similarly, this also makes it difficult to demonstrate an association between Ca Pancreas and other vital organs of the body, such as the heart. A number of studies have proven a correlation between the heart and pancreatic cancer. The tumor of the pancreas affects the heart at the physiological, as well as the molecular, level. An overexpression of the SMAD4 gene; a disruption in biomolecules, such as IGF, MAPK, and ApoE; and increased CA19-9 markers are a few of the many factors that are noted to affect cardiovascular systems with pancreatic malignancies. A comprehensive review of this correlation will aid researchers in conducting studies to help establish a definite relation between the two organs and discover ways to use it for the early detection of Ca Pancreas.
RESUMEN
The association and interaction between the central nervous system (CNS) and enteric nervous system (ENS) is well established. Essentially ENS is the second brain, as we call it. We tried to understand the structure and function, to throw light on the functional aspect of neurons, and address various disease manifestations. We summarized how various neurological disorders influence the gut via the enteric nervous system and/or bring anatomical or physiological changes in the enteric nervous system or the gut and vice versa. It is known that stress has an effect on Gastrointestinal (GI) motility and causes mucosal erosions. In our literature review, we found that stress can also affect sensory perception in the central nervous system. Interestingly, we found that mutations in the neurohormone, serotonin (5-HT), would result in dysfunctional organ development and further affect mood and behavior. We focused on the developmental aspects of neurons and cognition and their relation to nutritional absorption via the gastrointestinal tract, the development of neurodegenerative disorders in relation to the alteration in gut microbiota, and contrariwise associations between CNS disorders and ENS. This paper further summarizes the synergetic relation between gastrointestinal and neuropsychological manifestations and emphasizes the need to include behavioral therapies in management plans.
RESUMEN
Background: Primary-progressive multiple sclerosis (PPMS) and relapsing-remitting multiple sclerosis (RRMS) are two frequent multiple sclerosis (MS) subtypes that involve 10%-15% of patients. PPMS progresses slowly and is diagnosed later in life. Both subtypes are influenced by genetic and environmental factors such as smoking, obesity, and vitamin D insufficiency. Although there is no cure, ocrelizumab can reduce symptoms and delay disease development. RRMS is an autoimmune disease that causes inflammation, demyelination, and disability. Early detection, therapy, and lifestyle changes are critical. This study delves into genetics, immunology, biomarkers, neuroimaging, and the usefulness of ocrelizumab in the treatment of refractory patients of PPMS. Method: In search of published literature providing up-to-date information on PPMS and RRMS, this review conducted numerous searches in databases such as PubMed, Google Scholar, MEDLINE, and Scopus. We looked into genetics, immunology, biomarkers, current breakthroughs in neuroimaging, and the role of ocrelizumab in refractory cases. Results: Our comprehensive analysis found considerable advances in genetics, immunology, biomarkers, neuroimaging, and the efficacy of ocrelizumab in the treatment of refractory patients. Conclusion: Early detection, timely intervention, and the adoption of lifestyle modifications play pivotal roles in enhancing treatment outcomes. Notably, ocrelizumab has demonstrated potential in symptom control and mitigating the rate of disease advancement, further underscoring its clinical significance in the management of MS.
RESUMEN
Multiple sclerosis (MS) and myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS) share the symptom of fatigue, and might even coexist together. Specifically focusing on genetics, pathophysiology, and neuroimaging data, the authors discuss an overview of the parallels, correlation, and differences in fatigue between MS and ME/CFS along with ME/CFS presence in MS. Studies have revealed that the prefrontal cortex and basal ganglia regions, which are involved in fatigue regulation, have similar neuroimaging findings in the brains of people with both MS and ME/CFS. Additionally, in both conditions, genetic factors have been implicated, with particular genes known to enhance susceptibility to MS and CFS. Management approaches for fatigue in MS and ME/CFS differ based on the underlying factors contributing to fatigue. The authors also focus on the recent updates and the relationship between MS and sleep disorders, including restless legs syndrome, focusing on pathophysiology and therapeutic approaches. Latest therapeutic approaches like supervised physical activity and moderate-intensity exercises have shown better outcomes.
RESUMEN
The prevalence and incidence of Ulcerative Colitis (UC), a recurrent and remitting inflammatory condition, are rising. Any part of the colon may be affected, beginning with inflammation of the mucosa in the rectum and continuing proximally continuously. Bloody diarrhea, tenesmus, fecal urgency, and stomach pain are typical presenting symptoms. Many patients present with extraintestinal manifestations (EIMs) including musculoskeletal, ocular, renal, hepatobiliary, and dermatological presentation, among others. Most cases are treated with pharmacological therapy including mesalazine and glucocorticoids. Fecal microbiota transplantation (FMT) is a novel procedure that is increasingly being used to treat UC, however, its use yet remains controversial because of uncertain efficacy. FMT can lower gut permeability and consequently disease severity by boosting short-chain fatty acids production, helping in epithelial barrier integrity preservation. Upadacitinib (JAK Kinase inhibitor) is another newer treatment option, which is an FDA-approved drug that is being used to treat UC. This review article provides a comprehensive review of the EIMs of UC, the role of FMT along with various recent clinical trials pertaining to FMT as well as other diagnostic and therapeutic updates.
Asunto(s)
Colitis Ulcerosa , Humanos , Colitis Ulcerosa/terapia , Colitis Ulcerosa/diagnóstico , Trasplante de Microbiota Fecal/métodos , Heces , Inflamación , Resultado del TratamientoRESUMEN
Kawasaki disease is an acute, febrile disease that is not typically fatal if treated and affects infants and children more commonly. More than 80% of the afflicted patients are under the age of four. This disease most commonly affects coronary arteries. In a minority of cases, Aneurysms can burst or produce thrombosis, and they can cause infarction. The distinctive redness in the palms and soles of the feet might result from a delayed-type hypersensitivity reaction to a cross-reactive or recently discovered antigen (s). Autoantibodies against epithelial cells and smooth muscle cells are produced as a result of subsequent macromolecule synthesis and polyclonal white blood cell activation, which intensifies the redness. Kawasaki disease's clinical manifestations range from oral skin disease to the blistering of the mucosa, symptoms involving the hands and the feet, skin disease of the palms and soles, a desquamative rash, and cervical lymphatic tissue enlargement (so it is also referred to as tissue layer lymphatic tissue syndrome). Most untreated patients develop some vessel sequelae, from well-organized coronary inflammation to severe arterial blood vessel dilatation to giant artery aneurysms with rupture or occlusion, infarction, and thrombosis. With human gamma globulin administration, reasonable standards of medical care, and the use of analgesics, the speed of symptomatic progression and inflammatory artery changes are reduced. In this review, we have covered the immunology of Kawasaki disease, its biomarkers, and the neurological manifestations of this multisystem illness. We have also included a discussion on its pathogenesis, diagnosis, and treatment.
Asunto(s)
Síndrome Mucocutáneo Linfonodular , Lactante , Niño , Humanos , Síndrome Mucocutáneo Linfonodular/terapia , Síndrome Mucocutáneo Linfonodular/tratamiento farmacológico , Aspirina/uso terapéutico , Biomarcadores , Vasos Coronarios , Enfermedad Aguda , InmunidadRESUMEN
Dementia is a chronic progressive cognitive decline illness that results in functional impairment. Vascular dementia (VaD), second only to Alzheimer's disease (AD), is one of the most prevalent forms of dementia in the elderly (aged over 65 years), with a varied presentation and unpredictable disease development caused by cerebrovascular or cardiovascular illness. To get a better understanding of the changes occurring in the brain and to drive therapy efforts, new biomarkers for early and precise diagnosis of AD and VaD are required. In this review, Firstly, we describe the subtypes of vascular dementia, their clinical features, pathogenesis, genetics implemented, and their associated neuroimaging and biomarkers, while describing extensively the recent biomarkers discovered in the literature. Secondly, we describe some of the well-documented and other less-defined risk factors and their association and pathophysiology in relation to vascular dementia. Finally, we follow recent updates in the management of vascular dementia along with its association and differentiation from Alzheimer's disease. The aim of this review is to gather the scattered updates and the most recent changes in blood, CSF, and neuroimaging biomarkers related to the multiple subtypes of vascular dementia along with its association with Alzheimer's dementia and diabetes mellitus.
Asunto(s)
Enfermedad de Alzheimer , Demencia Vascular , Diabetes Mellitus , Anciano , Humanos , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/diagnóstico , Demencia Vascular/terapia , Demencia Vascular/complicaciones , Biomarcadores , NeuroimagenRESUMEN
Alzheimer's disease is a prevalent form of dementia, particularly among the elderly population. It is characterized by progressive cognitive decline and neurodegeneration. Despite numerous studies, the exact cause of Alzheimer's disease remains uncertain, and various theories have been proposed, including Aß amyloid deposition in the brain and tau protein hyper-phosphorylation. This review article explores the potential pathogenesis of Alzheimer's disease, focusing on the effects of derangements in the levels of vitamin B12, folate, and homocysteine, as well as the impact of oral bacteria causing periodontitis and insulin resistance, and their relationship to Alzheimer's. Studies have shown that high levels of homocysteine and low levels of vitamin B12 and folate, are associated with an increased risk of developing Alzheimer's disease. The article also explores the link between Alzheimer's disease and oral bacteria, specifically dental infections and periodontitis, which contribute to the inflammatory processes in the nervous system of Alzheimer's patients. There could be derangement in the insulin signaling further causing disruption in glucose metabolism within the brain, suggesting that Alzheimer's disease may represent a form of type 2 diabetes mellitus associated with the brain, commonly known as type 3 diabetes. Neuroimaging techniques, including MRI, PET, and tau PET, can identify the predictive characteristics of Alzheimer's disease, with amyloid PET being the most useful in ruling out the disease. The article concludes by stressing the importance of understanding genetic and neuroimaging factors in the diagnosing and treating Alzheimer's disease.