Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy / 罕见病研究

@#In recent years, spinal muscular atrophy (SMA) has made progress in multidisciplinary treatment and disease-modifying therapeutic drugs, so that the progress has significantly improved the survival and quality of life of the patients. However, no clinical practice guideline has developed for the management of SMA in adults and adolescents patients. Experts of multidisciplinary from a number of tertiary medical centers in China who specialize in the diagnosis and treatment of SMA have come to an agreement based on the evidence-based medicine. This guideline serves as instrumental reference for the standardized care of the Chinese SMA patients.

Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy / 罕见病研究

@#In recent years, spinal muscular atrophy (SMA) has made progress in multidisciplinary treatment and disease-modifying therapeutic drugs, so that the progress has significantly improved the survival and quality of life of the patients. However, no clinical practice guideline has developed for the management of SMA in adults and adolescents patients. Experts of multidisciplinary from a number of tertiary medical centers in China who specialize in the diagnosis and treatment of SMA have come to an agreement based on evidence-based medicine. This guideline serves as instrumental reference for the standardized care of the Chinese SMA patients.

Clinical Practice Guideline for Adolescent & Adult Patients with Spinal Muscular Atrophy / 罕见病研究

In recent years, spinal muscular atrophy (SMA) has made progress in multidisciplinary treatment and disease-modifying therapeutic drugs, so that the progress has significantly improved the survival and quality of life of the patients. However, no clinical practice guideline has developed for the management of SMA in adults and adolescents patients. Experts of multidisciplinary from a number of tertiary medical centers in China who specialize in the diagnosis and treatment of SMA have come to an agreement based on the evidence-based medicine. This guideline serves as instrumental reference for the standardized care of the Chinese SMA patients.

Evolution of no evidence of disease activity therapeutic goals of multiple sclerosis from new progress of nerve injury mechanisms / 中华神经科杂志

Multiple sclerosis is a severe autoimmune inflammatory disease mainly involving the central nervous system. In recent years, the exploration of the mechanism of nerve injury in multiple sclerosis has made great progress. At the same time, disease-modifying therapeutic drugs with different targets are also emerging. Understanding of the mechanisms of nerve injury in multiple sclerosis can help clinicians comprehensively understand the evolution of disease-modifying therapeutic targets of this disorder. Here, the mechanisms of nerve injury in multiple sclerosis and the relationship with the evolution of disease-modifying therapeutic targets are reviewed.

Recent advance in research on radiological isolated syndrome / 中华神经科杂志

Radiological isolated syndrome has been a hot topic in the field of neuroimmunology in recent years, but there were rare reports and reviews on this field in domestic literature. With the development of imaging technology and the proposed modified McDonald diagnostic criteria for multiple sclerosis in 2017, new perspectives have been proposed in diagnostic criteria, clinical research, functional imaging research and treatment strategies of radiological isolated syndrome. The purpose of this review is to improve the understanding of radiological isolated syndrome by sorting and summarizing the above contents.

Disease modifying therapy of pediatric neuromuscular diseases / 中国小儿急救医学

Neuromuscular diseases (NMDs) are a group of hereditary, commonly childhood-onset neurological disorders affecting various components of motor unit, which are often characterized by reduced muscle strength.With the rapid development of precision medicine, great progress has been made in the pharmacological treatment of NMDs, and pediatric NMDs has also entered the era of disease modifying therapy.Antisense oligonucleotides, gene therapy, small molecule compounds, monoclonal antibodies and other disease modifying therapy drugs targeting the cause and pathogenesis of the diseases are gradually applied in clinical practice.What′s more, a variety of potential new drugs and therapeutic biological products are in continuous development.Hopefully, new breakthroughs are expected to be achieved in the field of pediatric NMDs treatment in the near future.

Spinal Muscular Atrophy: History, Current Status and Future / 罕见病研究

It has been a hundred years since the first case of spinal muscular atrophy(SMA) was reported in the medical literature. In its 100 years of history, medical development for the cure of SMA has gone through many stages, from clinical manifestation description, accumulation of cases, disease classification exploration to pathogenic gene mapping and cloning, clinical application of gene diagnosis, animal model establishment then to R&D of disease modifying drugs and clinical use of novel therapies. The future of the development lies in breakthrough in pathophysiological mechanism, carrier screening and precise prevention, as well as new therapies. As a representative of monogenic rare diseases, review the history of the progress in diagnosis and treatment and R&D in medications and discuss the prospect of further development in the future is instrumental in leading the continued advancement of the whole cause of rare disease.

Disease-modifying therapy for multiply system atrophy / 中华老年医学杂志

Multiple system atrophy(MSA)is a rare and fatal neurodegenerative disease occurring in middle-aged and older people, mainly characterized by autonomic nervous system and motor dysfunction.At present, there is no effective method to prevent or reverse its progression, and its treatment is mostly symptom-based, with limited success.A large number of interventional trials have been conducted to explore new treatments for MSA, but there is no clearly effective disease-modifying therapy, probably as a result of poor understanding of the pathophysiological and physiological mechanisms underlying MSA, which may be influenced by multiple factors.The purpose of this paper is to review the existing intervention trials for disease modification therapy of MSA and to discuss the outlook for new therapeutic targets.

Real-World Effectiveness of Disease-Modifying Therapies in Korean Patients with Relapsing Multiple Sclerosis

BACKGROUND AND PURPOSE: This study assessed the long-term outcomes of disease-modifying therapies (DMTs) in Korean multiple sclerosis (MS) patients treated in real-world clinical settings in Korea. METHODS: We retrospectively evaluated the medical records of 160 patients with an initial diagnosis of clinically isolated syndrome or relapsing-remitting MS who were treated for at least 2 years. A status of 3 for no evidence of disease activity (NEDA3) was defined as no relapse, disability progression, or active lesions in annual magnetic resonance imaging (MRI) evaluations. RESULTS: Patients who were initially treated with interferon β (n=152), glatiramer acetate (n=6), or teriflunomide (n=2) were included. The mean disease duration was 8.2 years. Compared to pretreatment, annualized relapse rates were significantly reduced after treatment [from 1.0±0.8 to 0.2±0.4 (mean±standard deviation), p < 0.001]. At the follow-up, 79 patients (49%) had changed their treatment regimen due to lack of efficacy (33%), side effects (14%), or other reasons (2%). Disability progression was observed in 18% of the patients over a mean treatment duration of 5.7 years. After 2 years, NEDA3 was observed in 38% of the patients. Loss of NEDA3 at 2 years was associated with long-term disability progression [odds ratio (OR)=17.975, p=0.003]. Poor response to first-line treatment was independently associated with a delay in treatment from disease onset (OR=1.238, p=0.049) and 10 or more brain lesions in the initial MRI (OR=3.648, p=0.047). CONCLUSIONS: This study has provided real-world evidence that DMTs are effective in reducing disease activity and disability progression in Korean MS patients.

Guidelines for the management of Stevens–Johnson syndrome/toxic epidermal necrolysis: An Indian perspective.

Background: Stevens–Johnson syndrome and toxic epidermal necrolysis are severe, life‑threatening mucocutaneous adverse drug reactions with a high morbidity and mortality that require immediate medical care. The various immunomodulatory treatments include systemic corticosteroids, cyclosporine, intravenous immunoglobulin, cyclophosphamide, plasmapheresis and tumor necrosis factor‑α inhibitors. Aim: The ideal therapy of Stevens– Johnson syndrome/toxic epidermal necrolysis still remains a matter of debate as there are only a limited number of studies of good quality comparing the usefulness of different specific treatments. The aim of this article is to comprehensively review the published medical literature and frame management guidelines suitable in the Indian perspective. Methods: The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) assigned the task of preparing these guidelines to its special interest group on cutaneous adverse drug reactions. The group performed a comprehensive English language literature search for management options in Stevens–Johnson syndrome/toxic epidermal necrolysis across multiple databases (PubMed, EMBASE, MEDLINE and Cochrane) for keywords (alone and in combination) and MeSH items such as “guidelines,” “Stevens–Johnson syndrome,” “toxic epidermal necrolysis,” “corticosteroids,” “intravenous immunoglobulin,” “cyclosporine” and “management.” The available evidence was evaluated using the strength of recommendation taxonomy and graded using a three‑point scale. A draft of clinical recommendations was developed on the best available evidence which was also scrutinized and critically evaluated by the IADVL Academy of Dermatology. Based on the inputs received, this final consensus statement was prepared. Results: A total of 104 articles (meta‑analyses, prospective and retrospective studies, reviews [including chapters in books], previous guidelines [including Indian guidelines of 2006] and case series) were critically evaluated and the evidence thus gathered was used in the preparation of these guidelines. Recommendations: This expert group recommends prompt withdrawal of the culprit drug, meticulous supportive care, and judicious and early (preferably within 72 h) initiation of moderate to high doses of oral or parenteral corticosteroids (prednisolone 1‑2 mg/kg/day or equivalent), tapered rapidly within 7‑10 days. Cyclosporine (3‑5 mg/kg/day) for 10‑14 days may also be used either alone, or in combination with corticosteroids. Owing to the systemic nature of the disease, a multidisciplinary approach in the management of these patients is helpful.

Current concepts in the treatment of hereditary ataxias / Conceitos atuais no tratamento das ataxias hereditárias

ABSTRACT Hereditary ataxias (HA) represents an extensive group of clinically and genetically heterogeneous neurodegenerative diseases, characterized by progressive ataxia combined with extra-cerebellar and multi-systemic involvements, including peripheral neuropathy, pyramidal signs, movement disorders, seizures, and cognitive dysfunction. There is no effective treatment for HA, and management remains supportive and symptomatic. In this review, we will focus on the symptomatic treatment of the main autosomal recessive ataxias, autosomal dominant ataxias, X-linked cerebellar ataxias and mitochondrial ataxias. We describe management for different clinical symptoms, mechanism-based approaches, rehabilitation therapy, disease modifying therapy, future clinical trials and perspectives, genetic counseling and preimplantation genetic diagnosis.

RESUMO As ataxias hereditárias representam um grupo complexo de doenças neurodegenerativas, e se caracterizam por ataxia cerebelar progressiva, associada a sinais e sintomas extra-cerebelares e sistêmicos, os quais incluem: neuropatia periférica, sinais piramidais, distúrbios do movimento, convulsões e disfunção cognitiva. Não existe um tratamento efetivo para a cura das ataxias hereditárias. Até o momento os tratamentos disponíveis são apenas sintomáticos. Nesta revisão vamos abordar tratamento sintomático das principais ataxias autossômicas recessivas, ataxias autossômicas dominantes, ataxias ligadas ao X e ataxias mitocondriais. Descrevemos os diferentes sintomas, abordagens terapêuticas baseadas no mecanismo fisiopatológico, terapia de reabilitação, terapia modificadora da doença, futuros ensaios clínicos, perspectivas, níveis de evidência, aconselhamento genético e diagnóstico genético pré-implantacional.

Harnessing Cerebrospinal Fluid Biomarkers in Clinical Trials for Treating Alzheimer's and Parkinson's Diseases: Potential and Challenges

No disease-modifying therapies (DMT) for neurodegenerative diseases (NDs) have been established, particularly for Alzheimer's disease (AD) and Parkinson's disease (PD). It is unclear why candidate drugs that successfully demonstrate therapeutic effects in animal models fail to show disease-modifying effects in clinical trials. To overcome this hurdle, patients with homogeneous pathologies should be detected as early as possible. The early detection of AD patients using sufficiently tested biomarkers could demonstrate the potential usefulness of combining biomarkers with clinical measures as a diagnostic tool. Cerebrospinal fluid (CSF) biomarkers for NDs are being incorporated in clinical trials designed with the aim of detecting patients earlier, evaluating target engagement, collecting homogeneous patients, facilitating prevention trials, and testing the potential of surrogate markers relative to clinical measures. In this review we summarize the latest information on CSF biomarkers in NDs, particularly AD and PD, and their use in clinical trials. The large number of issues related to CSF biomarker measurements and applications has resulted in relatively few clinical trials on CSF biomarkers being conducted. However, the available CSF biomarker data obtained in clinical trials support the advantages of incorporating CSF biomarkers in clinical trials, even though the data have mostly been obtained in AD trials. We describe the current issues with and ongoing efforts for the use of CSF biomarkers in clinical trials and the plans to harness CSF biomarkers for the development of DMT and clinical routines. This effort requires nationwide, global, and multidisciplinary efforts in academia, industry, and regulatory agencies to facilitate a new era.

Recent Advances in Diagnosis and Treatment of Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder in which neuronal loss causes cognitive decline and other neuropsychiatric problems. It can be diagnosed based on history, examination, and appropriate objective assessments, using standard criteria such as the Diagnostic and Statistical Manual of Mental Disorders or the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA). Brain imaging and biomarkers are making progress in the differential diagnoses among the different disorders. The cholinesterase inhibitors, donepezil, rivastigmine and galantamine and N-methyl-D-aspartate receptors antagonist memantine are approved by the US Food and Drug Administration for AD. Recently some acetylcholinesterase inhibitors gained approval for the treatment of severe AD and became available in a higher dose formulation or a patch formulation. Optimal care in AD is multifactorial and it should include early diagnosis and multidisciplinary care with pharmacological and nonpharmacological interventions including exercise interventions, cognitive interventions and maintenance of social networks.

Novel Pharmacotherapies for Alzheimer's Disease

Alzheimer disease (AD) is pathologically characterized by extracellular amyloid deposits composed of beta-amyloid (A beta) peptide, neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau, and deficit of cholinergic neurons in the basal forebrain. It is the most common neurodegenerative disease in the elderly. With the aging of the population, the incidence and prevalence of AD will also increase rapidly. The subsequent growing socioeconomic burden seems to be inevitable until effective therapeutic strategies are developed. Currently available treatments approved by the US Food and Drug Administration, while ameliorating the symptoms, do not halt progression or cure the illness. AD is a multifactorial syndrome with several target proteins contributing to its etiology. In this review, various small molecules targeting pathological hall marks or their major constituents that have been reported in the literature will be discussed, with emphasis on compounds that are presently being investigated in clinical trials.