Gene therapy and antisense oligonucleotides (ASOs) are promising approaches to treating rare diseases by targeting specific genes. However, ASOs can have off-target effects that need careful consideration during devel...Gene therapy and antisense oligonucleotides (ASOs) are promising approaches to treating rare diseases by targeting specific genes. However, ASOs can have off-target effects that need careful consideration during development. Researchers can add moieties like peptide nucleic acid or methoxyethyl-modified ribose sugars to enhance specificity and reduce toxicity. Current research suggests that challenges such as nonspecific action, interference at various stages, adverse reactions, and nuclease degradation may soon be manageable with advanced technologies. ASOs show particular promise in treating rare conditions like Duchenne Muscular Dystrophy (DMD) and Timothy syndrome. Stereopure ASOs with repeated left-right patterns offer increased potency and half-life due to their resistance to nuclease activity and improved cellular uptake. This review explores how technological advancements can enhance the use of ASOs to manage various rare disease conditions effectively. Despite challenges in development and application, ASO therapy holds the potential to become a viable treatment option for a wide range of rare diseases. Advances in technology offer the possibility of increasing specificity and reducing toxicity, making ASO therapy a more effective and safe treatment option for patients with rare diseases.展开更多
Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, which is characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. Sufferers of...Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, which is characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. Sufferers of EB have compared the sores to third-degree burns. Stevens-Johnson syndrome is a rare but very serious skin problem, which causes the appearance of reddish lesions throughout the body and other changes, such as difficulty in breathing and fever, which can endanger the life of the affected person. The aim of this study was to show efficacy of a NANOSKIN ACT, AND NANOSKIN ACT SOFT wound dressing on the wound care management in patients with EB AND Stevens-Johnson syndrome (SJS).展开更多
The paper is to look at the affordability of orphan medications across the globe and whether payer attitudes to high-price medications are changing in the face of rising healthcare expenditure and tighter budgets. We ...The paper is to look at the affordability of orphan medications across the globe and whether payer attitudes to high-price medications are changing in the face of rising healthcare expenditure and tighter budgets. We conducted an online semi-quantitative survey of 10 European markets, the United States and Japan （Q1-Q2 2014） to understand how payers＇ views and attitudes are changing in response to new treatments coming to market for rare and ultra-rare conditions. The payers selected for the survey hold or have held senior positions within their respective market institutions. The United States and Japan were included in the study to provide international context to the European results. Responses were anonymised in accordance with good market research principles. The research shows that 75% of respondents surveyed believe that the current approach to orphan drug pricing is unsustainable in the future and 92% predict a tougher approach from payers going forward. 75% of payers do not believe that patent expiry alone will free up the necessary space for innovative orphan and ultra-orphan products. 83% of the payers surveyed believed that less than half of all orphan and ultra-orphan drugs coming to market are supported by an adequate evidence base for reimbursement. The environment for orphan medicines across the globe is changing; and as the financial performance of countries begins to diverge, so do attitudes towards the funding of orphan medicines. The increasing number of rare diseases, and treatments available, is forcing payers to view orphan drugs in a new light and they are becoming increasingly sceptical about the prices charged in relation to the clinical benefit offered. As rare disease spending becomes a higher proportion of pharmaceutical spending, payers will need to take action to curb this trend.展开更多
The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turk...The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turkey has made the relevant legal arrangements in 2020. The largest group under this common roof is “Hereditary Metabolic diseases”. The number of inherited metabolic diseases has reached a remarkable scope in the light of the rapidly accelerating developments in biochemistry, genetics, pharmacology, electronics sciences in 1902, when this name was first used, “Alkaptonuria” disease. In the light of the information obtained, 4 separate subgroups were created according to their common characteristics in order to produce solutions for this large group. Treatment options for metabolic disorders are both simple and complex. Diet therapy, cofactor therapy, enzyme replacement therapy (ERT), Substrate reduction therapy, chaperone therapy, tissue - organ - stem cell transplantation and gene therapy can be listed as these treatment options. Preimplantation genetics has been a rational solution to preventing disease formation, also supported by our ministry of health.展开更多
Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographi...Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographic search was carried out on the use of botanical drugs,rare disease drugs,related registration management policies and regulations in PubMed and CNKI.The following keywords were searched in the database:Rare disease policies and regulations,orphan drugs,botanical drugs for intractable diseases,botanical drugs for the treatment of new coronary pneumonia,traditional Chinese medicine,and emergency guidelines for major public health crisis.Other data were obtained from“Chinese Pharmacopoeia”and relevant Chinese government websites for sorting and analysis.Results and Conclusion Based on 39 Chinese corresponding policies and regulations,challenges and opportunities of developing and researching drugs for treating rare diseases were found out after the analysis and comparison.Based on the study of national policies on drugs for rare diseases,the priority review and approval procedures in the drug registration,as well as China’s emergency guidelines and policies for major public health events,some problems in the use of drugs for rare diseases are found out.Therefore,it is recommended to actively adopt the property rights protection system,explore the folk prescriptions of traditional Chinese medicine and the potential of hospital preparations,and the registration review strategy of giving priority to the use of botanical drugs for rare diseases.Thus,the international status of botanical drugs for rare disease and the influence of responding to major public health events can be enhanced.展开更多
Objective To study the use of real-world evidence by EU and its member states for establishing a strategy for rare diseases and provide references for the inclusion of orphan drugs in China’s medical insurance.Method...Objective To study the use of real-world evidence by EU and its member states for establishing a strategy for rare diseases and provide references for the inclusion of orphan drugs in China’s medical insurance.Methods A case analysis method was used to introduce the EU’s decision to include rare disease drugs in medical insurance by using real-world evidence because clinical data of rare diseases were difficult to obtain.Results and Conclusion China can use real-world evidence to make medical insurance decisions based on the experience of the EU and continue to invest more in rare diseases,which can solve the problem of few drugs for patients with rare disease.展开更多
The recent advances in high throughput sequencing technology have drastically changed the practice of medical diagnosis,allowing for rapid identification of hundreds of genes causing human diseases.This unprecedented ...The recent advances in high throughput sequencing technology have drastically changed the practice of medical diagnosis,allowing for rapid identification of hundreds of genes causing human diseases.This unprecedented progress has made clear that most forms of intellectual disability that affect more than 3%of individuals worldwide are monogenic dis-eases.Strikingly,a substantial fraction of the mendelian forms of intellectual disability is asso-ciated with genes related to the ubiquitin-proteasome system,a highly conserved pathway made up of approximately 1200 genes involved in the regulation of protein homeostasis.Within this group is currently emerging a new class of neurodevelopmental disorders specifically caused by proteasome pathogenic variants which we propose to designate"neurodevelopmen-tal proteasomopathies".Besides cognitive impairment,these diseases are typically associated with a series of syndromic clinical manifestations,among which facial dysmorphism,motor delay,and failure to thrive are the most prominent ones.While recent efforts have been made to uncover the effects exerted by proteasome variants on cell and tissue landscapes,the mo-lecular pathogenesis of neurodevelopmental proteasomopathies remains ill-defined.In this re-view,we discuss the cellular changes typically induced by genomic alterations in proteasome genes and explore their relevance as biomarkers for the diagnosis,management,and potential treatment of these new rare disease entities.展开更多
The onset of critical rare diseases(RDs)in children is rapid and dangerous,accompanied by a high mortality rate,which brings a heavy burden to both families and society.Multiple malformations,neuromuscular diseases,me...The onset of critical rare diseases(RDs)in children is rapid and dangerous,accompanied by a high mortality rate,which brings a heavy burden to both families and society.Multiple malformations,neuromuscular diseases,metabolic diseases,and heart diseases are the most common types of RDs in children of China,often manifesting with multiple organ dysfunction.At present,the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time,a high misdiagnosis rate,limited treatment modalities,and a significant disease burden.However,with the progress in genetic testing technology,the establishment of multidisciplinary diagnosis and treatment platforms,and the implementation of relevant RD policies in China,children with critical RDs will received enhanced medical services,experience improved prognoses,and reintegrate into social life.展开更多
Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein functio...Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.展开更多
Many patients with rare diseases not only suffer from more severe conditions but often receive less disease management, which is one significant public health concern globally. Few practice-based surveys focus on the ...Many patients with rare diseases not only suffer from more severe conditions but often receive less disease management, which is one significant public health concern globally. Few practice-based surveys focus on the care of patients with rare diseases. In the present study, we aimed to investigate medical service utilization, economic burden and health status of patients with rare diseases in China. A cross-sectional questionnaire survey focusing on patients with rare diseases was conducted. Descriptive analysis was conducted to examine the sociodemographic characteristics, medical service utilization, economic burden and health status. Logistic regression analysis was applied to explore influencing factors of self-rated health. A total of 982 patients with 81 types of diseases were included in this survey. We found that 58.2% of patients experienced misdiagnosis, and 35.2% of the patients were misdiagnosed for at least five times. Moreover, 65.8% of patients traveled to hospitals to seek medical services, and 92.1% of patients paid expenses for their treatment. However, only 1.3% of patients could afford their medical expenditure without debts, and 86.8% of patients regarded their health status as bad or moderate. Significant factors correlated with health status were economic status, gender, age, employment and household size. From this study, the accessibility of medical service utilization, the affordability of medical economic burden, and the condition of health status for patients with rare disease in China were considerably poor. Basic medical insurance did not play its role in improving the utilization of medical services and the affordability of medical costs. Social support should be encouraged to improve patients＇ health status.展开更多
Background： China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health se...Background： China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health services for patients with rare diseases in China. This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity. Methods： Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted. Individual and family information, health expenditure and reimbursement in 2014 of 982 patients were collected. The impact of medical insurance, individual sociodemographic characteristics, family characteristics, and healthcare need on total and out-of-pocket （OOP） health expenditures was analyzed through the generalized linear model. Equity of health expenditure was evaluated by both concentration index and Lorenz curve. Results： Of all the surveyed patients, 11.41% had no medical insurance and 92.10% spent money to seek medical treatment in 2014. It was suggested female （P = 0.048）, over 50 years of age （P = 0.062）, high-income group （P = 0.021）, hospitalization （P- 0.000）, and reimbursement ratio （RR） （P = 0.000） were positively correlated with total health expenditure. Diseases not needing long-term treatment （P = 0.000） was negatively correlated with total health expenditure. Over 50 years of age （P = 0.065）, high-income group （P = 0.018）, hospitalization （P = 0.000） and having Urban Employee Basic Medical Insurance （UEBMI） （P - 0.022） were positively correlated with OOP health expenditure. Patient or the head of the household having received higher education （P = 0.044 and P = 0.08 l） and reimbursement ratio （P = 0.078） were negatively correlated with OOP health expenditure. The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539, respectively. Conclusions： OOP health expenditure of patients with UEBMI was significantly more than that of patients without medical insurance. However, for any other medical insurance, there was no difference between OOP health expenditure of the insured patients and patients without insurance. The current reimbursement policies have increased the equity of health expenditure, but are biased toward high-income people.展开更多
Cystic fibrosis (CF) is an autosomal recessive disease that is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, an anion channel expressed on the epithelial surface (Rowe et al., 2005)...Cystic fibrosis (CF) is an autosomal recessive disease that is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, an anion channel expressed on the epithelial surface (Rowe et al., 2005). The dysfunction of Cl–anion channels leads to pathophysiological changes such as airway surface liquid (ASL) decrement, delayed mucociliary clearance and defective bacterial killing, resulting in infection, mucus obstruction, inflammation and bronchiectasis(Rowe et al., 2005).展开更多
The last Monday in February is the ＂Rare Disease Day＂ every year. This year the theme of it is ＂Join us in making the voice of rare diseases heard＂, proposed by World Health Organization （http：//www.rarediseased...The last Monday in February is the ＂Rare Disease Day＂ every year. This year the theme of it is ＂Join us in making the voice of rare diseases heard＂, proposed by World Health Organization （http：//www.rarediseaseday.org）. Rare diseases are a group of serious chronic diseases, with a high morbidity and mortality rates.展开更多
Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated...Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated to be nearly 400 million worldwide.Over the past decades, efforts from researchers, clinicians, and pharmaceutical industries have been focused on both the diagnosis and therapy of rare diseases. However, because of the lack of data and medical records for individual rare diseases and the high cost of orphan drug development, only limited progress has been achieved. In recent years, the rapid development of next-generation sequencing(NGS)-based technologies, as well as the popularity of precision medicine has facilitated a better understanding of rare diseases and their molecular etiology. As a result, molecular subclassification can be identified within each disease more clearly, significantly improving diagnostic accuracy. However, providing appropriate care for patients with rare diseases is still an enormous challenge. In this review, we provide a brief introduction to the challenges of rare disease research and make suggestions on where and how our efforts should be focused.展开更多
Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare.We aimed to determine health service utilization by Australian children with rare di...Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare.We aimed to determine health service utilization by Australian children with rare diseases and barriers to access-ing healthcare.Methods Parents completed an online survey on health professional and emergency department(ED)presentations,hospi-talization,and barriers to accessing services.Potential barriers to service access included residential location(city,regional,remote)and child health-related functioning,determined using a validated,parent-completed measure-of-function tool.Results Parents of 462 children with over 240 rare diseases completed the survey.Compared with the general population,these children were more likely to be hospitalized[odds ratio(OR)=17.25,95%confidence interval(CI)=15.50-19.20]and present to the ED(OR=4.15,95%CI=3.68-4.68)or a family physician(OR=4.14,95%CI=3.72-4.60).Child functional impairment was nil/mild(31%),moderate(48%)or severe(22%).Compared to children with nil/mild impair-ment,those with severe impairment were more likely to be hospitalized(OR=13.39,95%CI=7.65-23.44)and present to the ED(OR=11.16,95%CI=6.46-19.27).Most children(75%)lived in major cities,but children from regional(OR=2.78,95%CI=1.72-4.55)and remote areas(OR=9.09,95%CI=3.03-25.00)experienced significantly more barriers to healthcare access than children from major cities.Barriers included distance to travel,out-of-pocket costs,and lack of specialist medical and other health services.Conclusions Children with rare diseases,especially those with severe functional impairment have an enormous impact on health services,and better integrated multidisciplinary services with patient-centered care are needed.Access must be improved for children living in rural and remote settings.展开更多
The difficulty of converting scientific research findings into novel pharmacological treatments for rare and life-threatening diseases is enormous.Biomarkers related to multiple biological processes involved in cell g...The difficulty of converting scientific research findings into novel pharmacological treatments for rare and life-threatening diseases is enormous.Biomarkers related to multiple biological processes involved in cell growth,proliferation,and disease occurrence have been identified in recent years with the development of immunology,molecular biology,and genomics technologies.Biomarkers are capable of reflecting normal physiological processes,pathological processes,and the response to therapeutic intervention;as such,they play vital roles in disease diagnosis,prevention,drug response,and other aspects of biomedicine.The discovery of valuable biomarkers has become a focal point of current research.Numerous studies have identified molecular biomarkers based on the differential expression/concentration of molecules(e.g.,genes/proteins)for disease state diagnosis,characterization,and treatment.Although technological breakthroughs in molecular analysis platforms have enabled the identification of a large number of candidate biomarkers for rare diseases,only a small number of these candidates have been properly validated for use in patient treatment.The traditional molecular biomarkers may lose vital information by ignoring molecular associations/interactions,and thus the concept of network biomarkers based on differential associations/correlations of molecule pairs has been established.This approach promises to be more stable and reliable in diagnosing disease states.Furthermore,the newly-emerged dynamic network biomarkers(DNBs)based on differential fluctuations/correlations of molecular groups are able to recognize pre-disease states or critical states instead of disease states,thereby achieving rare disease prediction or predictive/preventative medicine and providing deep insight into the dynamic characteristics of disease initiation and progression.展开更多
Yang et al reported an immunocompetent infant with gastrointestinal cytomegalovirus disease secondary to measles infection.We express our opinion about the diagnosis and treatment of this rare disease.
BACKGROUND Pompe disease has a broad disease spectrum,including infantile-onset Pompe disease(IOPD)and late-onset Pompe disease(LOPD)forms.It is a type of glycogen storage disorder belonging to autosomal recessive gen...BACKGROUND Pompe disease has a broad disease spectrum,including infantile-onset Pompe disease(IOPD)and late-onset Pompe disease(LOPD)forms.It is a type of glycogen storage disorder belonging to autosomal recessive genetic disease,for an estimated incidence of 1/40000 among the neonatal population.In severe cases,the natural course is characterized by death due to cardiopulmonary failure in the first year after birth.However,the clinical outcomes have improved since the emergence of enzyme replacement therapy(ERT)was widely used.CASE SUMMARY The reported female case in China was an atypical IOPD,which demonstrates an unusual presentation of glycogen accumulation syndrome typeⅡwithout obvious skeletal muscle involvement,and reviewed physical examination,biochemical examinations,chest radiograph,and acidα-glucosidase(GAA)mutation analysis.After 4-mo specific ERT,the case received 12-mo follow-up.Moreover,the patient has obtained a very good prognosis under ERT.CONCLUSION For the atypical IOPD patients,early diagnosis and treatment may contribute to good prognosis.展开更多
BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11(STK11/LKB1)gene mutations.Preimplantation genetic testing can protect a patient’s offsp...BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11(STK11/LKB1)gene mutations.Preimplantation genetic testing can protect a patient’s offspring from mutated genes;however,some variations in this gene have been interpreted as variants of uncertain significance(VUS),which complicate reproductive decision-making in genetic counseling.AIM To identify the pathogenicity of two missense variants and provide clinical guidance.METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya.Software was employed to predict the protein structure,conservation,and pathogenicity of the two missense variation sites in patients with PJS.Additionally,plasmids were constructed and transfected into HeLa cells to observe cell growth.The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry.Statistical analysis was performed using one-way analysis of variance.P<0.05 was considered statistically significant.RESULTS We identified two missense STK11 gene VUS[c.889A>G(p.Arg297Gly)and c.733C>T(p.Leu245Phe)]in 9 unrelated PJS families who were seeking reproductive assistance.The two missense VUS were located in the catalytic domain of serine/threonine kinase,which is a key structure of the liver kinase B1(LKB1)protein.In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase(AMPK)at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells.In addition,the two missense STK11 variants promoted the proliferation of HeLa cells.Subsequent immunohistochemical analysis showed that phosphorylated-AMPK(Thr172)expression was significantly lower in gastric,colonic,and uterine polyps from PJS patients with missense variations than in non-PJS patients.Our findings indicate that these two missense STK11 variants are likely pathogenic and inactivate the STK11 gene,causing it to lose its function of regulating downstream phosphorylated-AMPK(Thr172),which may lead to the development of PJS.The identification of the pathogenic mutations in these two clinically characterized PJS patients has been helpful in guiding them toward the most appropriate mode of pregnancy assistance.CONCLUSION These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients.These findings not only offer insights for clinical decision-making,but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.展开更多
BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis main...BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells.Cases in which the liver is the primary organ affected by amyloidosis,as in this report,are less common in clinical practice.CASE SUMMARY A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes.His condition persisted,and he developed chronic liver failure,with severe cholestasis in the later stage that was gradually accompanied by renal injury.Ultimately,he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination.CONCLUSION Hepatic amyloidosis rarely occurs in the clinic,and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.展开更多
文摘Gene therapy and antisense oligonucleotides (ASOs) are promising approaches to treating rare diseases by targeting specific genes. However, ASOs can have off-target effects that need careful consideration during development. Researchers can add moieties like peptide nucleic acid or methoxyethyl-modified ribose sugars to enhance specificity and reduce toxicity. Current research suggests that challenges such as nonspecific action, interference at various stages, adverse reactions, and nuclease degradation may soon be manageable with advanced technologies. ASOs show particular promise in treating rare conditions like Duchenne Muscular Dystrophy (DMD) and Timothy syndrome. Stereopure ASOs with repeated left-right patterns offer increased potency and half-life due to their resistance to nuclease activity and improved cellular uptake. This review explores how technological advancements can enhance the use of ASOs to manage various rare disease conditions effectively. Despite challenges in development and application, ASO therapy holds the potential to become a viable treatment option for a wide range of rare diseases. Advances in technology offer the possibility of increasing specificity and reducing toxicity, making ASO therapy a more effective and safe treatment option for patients with rare diseases.
文摘Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, which is characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. Sufferers of EB have compared the sores to third-degree burns. Stevens-Johnson syndrome is a rare but very serious skin problem, which causes the appearance of reddish lesions throughout the body and other changes, such as difficulty in breathing and fever, which can endanger the life of the affected person. The aim of this study was to show efficacy of a NANOSKIN ACT, AND NANOSKIN ACT SOFT wound dressing on the wound care management in patients with EB AND Stevens-Johnson syndrome (SJS).
文摘The paper is to look at the affordability of orphan medications across the globe and whether payer attitudes to high-price medications are changing in the face of rising healthcare expenditure and tighter budgets. We conducted an online semi-quantitative survey of 10 European markets, the United States and Japan （Q1-Q2 2014） to understand how payers＇ views and attitudes are changing in response to new treatments coming to market for rare and ultra-rare conditions. The payers selected for the survey hold or have held senior positions within their respective market institutions. The United States and Japan were included in the study to provide international context to the European results. Responses were anonymised in accordance with good market research principles. The research shows that 75% of respondents surveyed believe that the current approach to orphan drug pricing is unsustainable in the future and 92% predict a tougher approach from payers going forward. 75% of payers do not believe that patent expiry alone will free up the necessary space for innovative orphan and ultra-orphan products. 83% of the payers surveyed believed that less than half of all orphan and ultra-orphan drugs coming to market are supported by an adequate evidence base for reimbursement. The environment for orphan medicines across the globe is changing; and as the financial performance of countries begins to diverge, so do attitudes towards the funding of orphan medicines. The increasing number of rare diseases, and treatments available, is forcing payers to view orphan drugs in a new light and they are becoming increasingly sceptical about the prices charged in relation to the clinical benefit offered. As rare disease spending becomes a higher proportion of pharmaceutical spending, payers will need to take action to curb this trend.
文摘The term rare disease is used for diseases with a prevalence of ˂ 1 per 2000 people in the community. For the first time in 1990, Sweden became the country that established an information center on rare diseases. Turkey has made the relevant legal arrangements in 2020. The largest group under this common roof is “Hereditary Metabolic diseases”. The number of inherited metabolic diseases has reached a remarkable scope in the light of the rapidly accelerating developments in biochemistry, genetics, pharmacology, electronics sciences in 1902, when this name was first used, “Alkaptonuria” disease. In the light of the information obtained, 4 separate subgroups were created according to their common characteristics in order to produce solutions for this large group. Treatment options for metabolic disorders are both simple and complex. Diet therapy, cofactor therapy, enzyme replacement therapy (ERT), Substrate reduction therapy, chaperone therapy, tissue - organ - stem cell transplantation and gene therapy can be listed as these treatment options. Preimplantation genetics has been a rational solution to preventing disease formation, also supported by our ministry of health.
文摘Objective To study the feasibility of developing botanical drugs to treat intractable diseases and play an important role in dealing with major public health crises.Methods From January 1990 to May 2021,a bibliographic search was carried out on the use of botanical drugs,rare disease drugs,related registration management policies and regulations in PubMed and CNKI.The following keywords were searched in the database:Rare disease policies and regulations,orphan drugs,botanical drugs for intractable diseases,botanical drugs for the treatment of new coronary pneumonia,traditional Chinese medicine,and emergency guidelines for major public health crisis.Other data were obtained from“Chinese Pharmacopoeia”and relevant Chinese government websites for sorting and analysis.Results and Conclusion Based on 39 Chinese corresponding policies and regulations,challenges and opportunities of developing and researching drugs for treating rare diseases were found out after the analysis and comparison.Based on the study of national policies on drugs for rare diseases,the priority review and approval procedures in the drug registration,as well as China’s emergency guidelines and policies for major public health events,some problems in the use of drugs for rare diseases are found out.Therefore,it is recommended to actively adopt the property rights protection system,explore the folk prescriptions of traditional Chinese medicine and the potential of hospital preparations,and the registration review strategy of giving priority to the use of botanical drugs for rare diseases.Thus,the international status of botanical drugs for rare disease and the influence of responding to major public health events can be enhanced.
文摘Objective To study the use of real-world evidence by EU and its member states for establishing a strategy for rare diseases and provide references for the inclusion of orphan drugs in China’s medical insurance.Methods A case analysis method was used to introduce the EU’s decision to include rare disease drugs in medical insurance by using real-world evidence because clinical data of rare diseases were difficult to obtain.Results and Conclusion China can use real-world evidence to make medical insurance decisions based on the experience of the EU and continue to invest more in rare diseases,which can solve the problem of few drugs for patients with rare disease.
基金supported by the European Joint Programme on Rare Diseases (EJP RD)for the project"UPS-NDDiag"and the Agence Nationale de la Recherche (ANR)for the project ANR-21-CE17-0005.
文摘The recent advances in high throughput sequencing technology have drastically changed the practice of medical diagnosis,allowing for rapid identification of hundreds of genes causing human diseases.This unprecedented progress has made clear that most forms of intellectual disability that affect more than 3%of individuals worldwide are monogenic dis-eases.Strikingly,a substantial fraction of the mendelian forms of intellectual disability is asso-ciated with genes related to the ubiquitin-proteasome system,a highly conserved pathway made up of approximately 1200 genes involved in the regulation of protein homeostasis.Within this group is currently emerging a new class of neurodevelopmental disorders specifically caused by proteasome pathogenic variants which we propose to designate"neurodevelopmen-tal proteasomopathies".Besides cognitive impairment,these diseases are typically associated with a series of syndromic clinical manifestations,among which facial dysmorphism,motor delay,and failure to thrive are the most prominent ones.While recent efforts have been made to uncover the effects exerted by proteasome variants on cell and tissue landscapes,the mo-lecular pathogenesis of neurodevelopmental proteasomopathies remains ill-defined.In this re-view,we discuss the cellular changes typically induced by genomic alterations in proteasome genes and explore their relevance as biomarkers for the diagnosis,management,and potential treatment of these new rare disease entities.
基金National Key Clinical Specialty Construction Project:Grant/Award Number:2021-451Beijing Major Epidemic Prevention and Control Key Specialty Outstanding Project:Grant/Award Number:2021-135。
文摘The onset of critical rare diseases(RDs)in children is rapid and dangerous,accompanied by a high mortality rate,which brings a heavy burden to both families and society.Multiple malformations,neuromuscular diseases,metabolic diseases,and heart diseases are the most common types of RDs in children of China,often manifesting with multiple organ dysfunction.At present,the diagnosis and treatment of critical RDs in children face challenges such as prolonged diagnosis time,a high misdiagnosis rate,limited treatment modalities,and a significant disease burden.However,with the progress in genetic testing technology,the establishment of multidisciplinary diagnosis and treatment platforms,and the implementation of relevant RD policies in China,children with critical RDs will received enhanced medical services,experience improved prognoses,and reintegrate into social life.
基金supported by Warren Alpert Foundation and Houston Methodist Academic Institute Laboratory Operating Fund(to HLC).
文摘Rare neurological diseases,while individually are rare,collectively impact millions globally,leading to diverse and often severe neurological symptoms.Often attributed to genetic mutations that disrupt protein function or structure,understanding their genetic basis is crucial for accurate diagnosis and targeted therapies.To investigate the underlying pathogenesis of these conditions,researchers often use non-mammalian model organisms,such as Drosophila(fruit flies),which is valued for their genetic manipulability,cost-efficiency,and preservation of genes and biological functions across evolutionary time.Genetic tools available in Drosophila,including CRISPR-Cas9,offer a means to manipulate gene expression,allowing for a deep exploration of the genetic underpinnings of rare neurological diseases.Drosophila boasts a versatile genetic toolkit,rapid generation turnover,and ease of large-scale experimentation,making it an invaluable resource for identifying potential drug candidates.Researchers can expose flies carrying disease-associated mutations to various compounds,rapidly pinpointing promising therapeutic agents for further investigation in mammalian models and,ultimately,clinical trials.In this comprehensive review,we explore rare neurological diseases where fly research has significantly contributed to our understanding of their genetic basis,pathophysiology,and potential therapeutic implications.We discuss rare diseases associated with both neuron-expressed and glial-expressed genes.Specific cases include mutations in CDK19 resulting in epilepsy and developmental delay,mutations in TIAM1 leading to a neurodevelopmental disorder with seizures and language delay,and mutations in IRF2BPL causing seizures,a neurodevelopmental disorder with regression,loss of speech,and abnormal movements.And we explore mutations in EMC1 related to cerebellar atrophy,visual impairment,psychomotor retardation,and gain-of-function mutations in ACOX1 causing Mitchell syndrome.Loss-of-function mutations in ACOX1 result in ACOX1 deficiency,characterized by very-long-chain fatty acid accumulation and glial degeneration.Notably,this review highlights how modeling these diseases in Drosophila has provided valuable insights into their pathophysiology,offering a platform for the rapid identification of potential therapeutic interventions.Rare neurological diseases involve a wide range of expression systems,and sometimes common phenotypes can be found among different genes that cause abnormalities in neurons or glia.Furthermore,mutations within the same gene may result in varying functional outcomes,such as complete loss of function,partial loss of function,or gain-of-function mutations.The phenotypes observed in patients can differ significantly,underscoring the complexity of these conditions.In conclusion,Drosophila represents an indispensable and cost-effective tool for investigating rare neurological diseases.By facilitating the modeling of these conditions,Drosophila contributes to a deeper understanding of their genetic basis,pathophysiology,and potential therapies.This approach accelerates the discovery of promising drug candidates,ultimately benefiting patients affected by these complex and understudied diseases.
文摘Many patients with rare diseases not only suffer from more severe conditions but often receive less disease management, which is one significant public health concern globally. Few practice-based surveys focus on the care of patients with rare diseases. In the present study, we aimed to investigate medical service utilization, economic burden and health status of patients with rare diseases in China. A cross-sectional questionnaire survey focusing on patients with rare diseases was conducted. Descriptive analysis was conducted to examine the sociodemographic characteristics, medical service utilization, economic burden and health status. Logistic regression analysis was applied to explore influencing factors of self-rated health. A total of 982 patients with 81 types of diseases were included in this survey. We found that 58.2% of patients experienced misdiagnosis, and 35.2% of the patients were misdiagnosed for at least five times. Moreover, 65.8% of patients traveled to hospitals to seek medical services, and 92.1% of patients paid expenses for their treatment. However, only 1.3% of patients could afford their medical expenditure without debts, and 86.8% of patients regarded their health status as bad or moderate. Significant factors correlated with health status were economic status, gender, age, employment and household size. From this study, the accessibility of medical service utilization, the affordability of medical economic burden, and the condition of health status for patients with rare disease in China were considerably poor. Basic medical insurance did not play its role in improving the utilization of medical services and the affordability of medical costs. Social support should be encouraged to improve patients＇ health status.
文摘Background： China has not established social security system for rare diseases. Rare diseases could easily impoverish patients and their families. Little research has studied the equity and accessibility of health services for patients with rare diseases in China. This study aimed to explore the factors that influence health expenditure of rare diseases and evaluate its equity. Methods： Questionnaire survey about living conditions and cost burden of patients with rare diseases was conducted. Individual and family information, health expenditure and reimbursement in 2014 of 982 patients were collected. The impact of medical insurance, individual sociodemographic characteristics, family characteristics, and healthcare need on total and out-of-pocket （OOP） health expenditures was analyzed through the generalized linear model. Equity of health expenditure was evaluated by both concentration index and Lorenz curve. Results： Of all the surveyed patients, 11.41% had no medical insurance and 92.10% spent money to seek medical treatment in 2014. It was suggested female （P = 0.048）, over 50 years of age （P = 0.062）, high-income group （P = 0.021）, hospitalization （P- 0.000）, and reimbursement ratio （RR） （P = 0.000） were positively correlated with total health expenditure. Diseases not needing long-term treatment （P = 0.000） was negatively correlated with total health expenditure. Over 50 years of age （P = 0.065）, high-income group （P = 0.018）, hospitalization （P = 0.000） and having Urban Employee Basic Medical Insurance （UEBMI） （P - 0.022） were positively correlated with OOP health expenditure. Patient or the head of the household having received higher education （P = 0.044 and P = 0.08 l） and reimbursement ratio （P = 0.078） were negatively correlated with OOP health expenditure. The equity evaluation found concentration indexes of health expenditure before and after reimbursement were 0.0550 and 0.0539, respectively. Conclusions： OOP health expenditure of patients with UEBMI was significantly more than that of patients without medical insurance. However, for any other medical insurance, there was no difference between OOP health expenditure of the insured patients and patients without insurance. The current reimbursement policies have increased the equity of health expenditure, but are biased toward high-income people.
文摘Cystic fibrosis (CF) is an autosomal recessive disease that is caused by mutations in the CF transmembrane conductance regulator (CFTR) protein, an anion channel expressed on the epithelial surface (Rowe et al., 2005). The dysfunction of Cl–anion channels leads to pathophysiological changes such as airway surface liquid (ASL) decrement, delayed mucociliary clearance and defective bacterial killing, resulting in infection, mucus obstruction, inflammation and bronchiectasis(Rowe et al., 2005).
文摘The last Monday in February is the ＂Rare Disease Day＂ every year. This year the theme of it is ＂Join us in making the voice of rare diseases heard＂, proposed by World Health Organization （http：//www.rarediseaseday.org）. Rare diseases are a group of serious chronic diseases, with a high morbidity and mortality rates.
基金supported by the National High Technology Research and Development Program of China (2015AA020108, 2015AA020104)the National Science Foundation of China (31671377)Shanghai 111 Project (B14019)
文摘Characterized by their low prevalence, rare diseases are often chronically debilitating or life threatening. Despite their low prevalence, the aggregate number of individuals suffering from a rare disease is estimated to be nearly 400 million worldwide.Over the past decades, efforts from researchers, clinicians, and pharmaceutical industries have been focused on both the diagnosis and therapy of rare diseases. However, because of the lack of data and medical records for individual rare diseases and the high cost of orphan drug development, only limited progress has been achieved. In recent years, the rapid development of next-generation sequencing(NGS)-based technologies, as well as the popularity of precision medicine has facilitated a better understanding of rare diseases and their molecular etiology. As a result, molecular subclassification can be identified within each disease more clearly, significantly improving diagnostic accuracy. However, providing appropriate care for patients with rare diseases is still an enormous challenge. In this review, we provide a brief introduction to the challenges of rare disease research and make suggestions on where and how our efforts should be focused.
基金an Australian Research Council Linkage Project grant scheme(No.LP110200277)The funding sources had no role in the study design+5 种基金in the collection,analysis and interpretation of datain the writing of the reportand in the decision to submit the paper for publication.During the period of the research,ZY held a Fellowship from the Sydney Medical School Foundation and LH was funded by a National Health and Medical Research Council of Australia Senior Research Fellowship(No.1117105)EJE was supported by a National Health and Medical Research Council of Australia Practitioner Fellowship(No.1021480)a Medical Research Futures Fund Next Generation Fellowship(No.1135959)CJ's Chair in Genomic Medicine is supported by The Royal Children's Hospital Foundation.
文摘Background Children with rare diseases experience challenges at home and school and frequently require multi-disciplinary healthcare.We aimed to determine health service utilization by Australian children with rare diseases and barriers to access-ing healthcare.Methods Parents completed an online survey on health professional and emergency department(ED)presentations,hospi-talization,and barriers to accessing services.Potential barriers to service access included residential location(city,regional,remote)and child health-related functioning,determined using a validated,parent-completed measure-of-function tool.Results Parents of 462 children with over 240 rare diseases completed the survey.Compared with the general population,these children were more likely to be hospitalized[odds ratio(OR)=17.25,95%confidence interval(CI)=15.50-19.20]and present to the ED(OR=4.15,95%CI=3.68-4.68)or a family physician(OR=4.14,95%CI=3.72-4.60).Child functional impairment was nil/mild(31%),moderate(48%)or severe(22%).Compared to children with nil/mild impair-ment,those with severe impairment were more likely to be hospitalized(OR=13.39,95%CI=7.65-23.44)and present to the ED(OR=11.16,95%CI=6.46-19.27).Most children(75%)lived in major cities,but children from regional(OR=2.78,95%CI=1.72-4.55)and remote areas(OR=9.09,95%CI=3.03-25.00)experienced significantly more barriers to healthcare access than children from major cities.Barriers included distance to travel,out-of-pocket costs,and lack of specialist medical and other health services.Conclusions Children with rare diseases,especially those with severe functional impairment have an enormous impact on health services,and better integrated multidisciplinary services with patient-centered care are needed.Access must be improved for children living in rural and remote settings.
基金National Key Research and Development Program of China[2017YFA0505500]Strategic Priority Research Program of the Chinese Academy of Sciences[XDB38040400]+3 种基金National Natural Science Foundation of China(NSFC)[12131020,31930022,12026608]Special Fund for Science and Technology Innovation Strategy of Guangdong Province[2021B0909050004,2021B0909060002]Major Key Project of Peng Cheng Laboratory[PCL2021A12]JST Moonshot R&D[JPMJMS2021].
文摘The difficulty of converting scientific research findings into novel pharmacological treatments for rare and life-threatening diseases is enormous.Biomarkers related to multiple biological processes involved in cell growth,proliferation,and disease occurrence have been identified in recent years with the development of immunology,molecular biology,and genomics technologies.Biomarkers are capable of reflecting normal physiological processes,pathological processes,and the response to therapeutic intervention;as such,they play vital roles in disease diagnosis,prevention,drug response,and other aspects of biomedicine.The discovery of valuable biomarkers has become a focal point of current research.Numerous studies have identified molecular biomarkers based on the differential expression/concentration of molecules(e.g.,genes/proteins)for disease state diagnosis,characterization,and treatment.Although technological breakthroughs in molecular analysis platforms have enabled the identification of a large number of candidate biomarkers for rare diseases,only a small number of these candidates have been properly validated for use in patient treatment.The traditional molecular biomarkers may lose vital information by ignoring molecular associations/interactions,and thus the concept of network biomarkers based on differential associations/correlations of molecule pairs has been established.This approach promises to be more stable and reliable in diagnosing disease states.Furthermore,the newly-emerged dynamic network biomarkers(DNBs)based on differential fluctuations/correlations of molecular groups are able to recognize pre-disease states or critical states instead of disease states,thereby achieving rare disease prediction or predictive/preventative medicine and providing deep insight into the dynamic characteristics of disease initiation and progression.
文摘Yang et al reported an immunocompetent infant with gastrointestinal cytomegalovirus disease secondary to measles infection.We express our opinion about the diagnosis and treatment of this rare disease.
基金Supported by Tianjin Municipal Health Commission,China,No. ZC20060
文摘BACKGROUND Pompe disease has a broad disease spectrum,including infantile-onset Pompe disease(IOPD)and late-onset Pompe disease(LOPD)forms.It is a type of glycogen storage disorder belonging to autosomal recessive genetic disease,for an estimated incidence of 1/40000 among the neonatal population.In severe cases,the natural course is characterized by death due to cardiopulmonary failure in the first year after birth.However,the clinical outcomes have improved since the emergence of enzyme replacement therapy(ERT)was widely used.CASE SUMMARY The reported female case in China was an atypical IOPD,which demonstrates an unusual presentation of glycogen accumulation syndrome typeⅡwithout obvious skeletal muscle involvement,and reviewed physical examination,biochemical examinations,chest radiograph,and acidα-glucosidase(GAA)mutation analysis.After 4-mo specific ERT,the case received 12-mo follow-up.Moreover,the patient has obtained a very good prognosis under ERT.CONCLUSION For the atypical IOPD patients,early diagnosis and treatment may contribute to good prognosis.
基金Supported by the Natural Science Foundation of Hunan Province,China,No.2023JJ30422.
文摘BACKGROUND Peutz-Jeghers syndrome(PJS)is a rare hereditary neoplastic disorder mainly associated with serine/threonine kinase 11(STK11/LKB1)gene mutations.Preimplantation genetic testing can protect a patient’s offspring from mutated genes;however,some variations in this gene have been interpreted as variants of uncertain significance(VUS),which complicate reproductive decision-making in genetic counseling.AIM To identify the pathogenicity of two missense variants and provide clinical guidance.METHODS Whole exome gene sequencing and Sanger sequencing were performed on the peripheral blood of patients with PJS treated at the Reproductive and Genetic Hospital of Citic-Xiangya.Software was employed to predict the protein structure,conservation,and pathogenicity of the two missense variation sites in patients with PJS.Additionally,plasmids were constructed and transfected into HeLa cells to observe cell growth.The differences in signal pathway expression between the variant group and the wild-type group were compared using western blot and immunohistochemistry.Statistical analysis was performed using one-way analysis of variance.P<0.05 was considered statistically significant.RESULTS We identified two missense STK11 gene VUS[c.889A>G(p.Arg297Gly)and c.733C>T(p.Leu245Phe)]in 9 unrelated PJS families who were seeking reproductive assistance.The two missense VUS were located in the catalytic domain of serine/threonine kinase,which is a key structure of the liver kinase B1(LKB1)protein.In vitro experiments showed that the phosphorylation levels of adenosine monophosphate-activated protein kinase(AMPK)at Thr172 and LKB1 at Ser428 were significantly higher in transfected variation-type cells than in wild-type cells.In addition,the two missense STK11 variants promoted the proliferation of HeLa cells.Subsequent immunohistochemical analysis showed that phosphorylated-AMPK(Thr172)expression was significantly lower in gastric,colonic,and uterine polyps from PJS patients with missense variations than in non-PJS patients.Our findings indicate that these two missense STK11 variants are likely pathogenic and inactivate the STK11 gene,causing it to lose its function of regulating downstream phosphorylated-AMPK(Thr172),which may lead to the development of PJS.The identification of the pathogenic mutations in these two clinically characterized PJS patients has been helpful in guiding them toward the most appropriate mode of pregnancy assistance.CONCLUSION These two missense variants can be interpreted as likely pathogenic variants that mediated the onset of PJS in the two patients.These findings not only offer insights for clinical decision-making,but also serve as a foundation for further research and reanalysis of missense VUS in rare diseases.
基金Natural Science Foundation of Hubei Province,China,No.2022CFB120.
文摘BACKGROUND Amyloidosis is a rare disorder that can be classified into various types,and the most common type is the systemic light chain type.The prognosis of this disease is extremely poor.In general,amyloidosis mainly affects the kidneys and heart and manifests as abnormal proliferation of clonal plasma cells.Cases in which the liver is the primary organ affected by amyloidosis,as in this report,are less common in clinical practice.CASE SUMMARY A 62-year-old man was admitted with persistent liver dysfunction of unknown cause and poor treatment outcomes.His condition persisted,and he developed chronic liver failure,with severe cholestasis in the later stage that was gradually accompanied by renal injury.Ultimately,he was diagnosed with hepatic amyloidosis through liver biopsy and pathological examination.CONCLUSION Hepatic amyloidosis rarely occurs in the clinic,and liver biopsy and pathological examination can assist in the accurate and effective diagnosis of this condition.
