Therapeutic advances in rare disease最新文献

{"title":"Quality of life in Barth syndrome.","authors":"Alexander Y Kim,&nbsp;Hilary Vernon,&nbsp;Ryan Manuel,&nbsp;Mohammed Almuqbil,&nbsp;Brittany Hornby","doi":"10.1177/26330040221093743","DOIUrl":"10.1177/26330040221093743","url":null,"abstract":"<p><strong>Introduction: </strong>Barth syndrome (BTHS) is a rare X-linked disorder characterized by cardiomyopathy, neutropenia, growth abnormalities, and skeletal myopathy. There have been few studies investigating health-related quality of life (HRQoL) in this population. This study investigated the impact of BTHS on HRQoL and select physiologic measures in affected boys and men.</p><p><strong>Methods: </strong>In this study, we characterize HRQoL in boys and men with BTHS through cross-sectional analysis of a variety of outcome measures including the Pediatric Quality of Life Inventory (PedsQL^TM) Version 4.0 Generic Core Scales, PedsQL^TM Multidimensional Fatigue Scale, Barth Syndrome Symptom Assessment, the PROMIS^TM Fatigue Short Form, the EuroQol Group EQ-5D^TM, the Patient Global Impression of Symptoms (PGIS), and the Caregiver Global Impression of Symptoms (CaGIS). For a specific subset of participants, physiologic data were available in addition to HRQoL data.</p><p><strong>Results: </strong>For the PedsQL^TM questionnaires, 18 unique child and parent reports were analyzed for children aged 5-18 years, and nine unique parent reports were analyzed for children aged 2-4 years. For the other HRQoL outcome measures and physiologic measurements, the data from 12 subjects (age range 12-35 years) were analyzed. Based on parent and child reports, HRQoL is significantly impaired in boys and men with BTHS, especially in school functioning and physical functioning. Parent and child reports of more severe fatigue are significantly correlated with more impaired HRQoL. When exploring the potential relationship between physiology and HRQoL, the CaGIS as a whole for pediatric subjects and individual questionnaire items from the PGIS and CaGIS for pediatric subjects assessing tiredness, muscle weakness, and muscle pain showed the strongest correlations.</p><p><strong>Conclusion: </strong>This study provides a unique characterization of the HRQoL in boys and men with BTHS using a variety of outcome measures, and it highlights the negative impact of fatigue and muscle weakness on HRQoL in BTHS.</p><p><strong>Trial registry name: </strong>A Trial to Evaluate Safety, Tolerability and Efficacy of Elamipretide in Subjects with Barth Syndrome (TAZPOWER). https://clinicaltrials.gov/ct2/show/NCT03098797.Registration Number: NCT03098797.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221093743"},"PeriodicalIF":0.0,"publicationDate":"2022-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/6f/34/10.1177_26330040221093743.PMC10032447.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469865","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Future of genetic therapies for rare genetic diseases: what to expect for the next 15 years?","authors":"Luiza Amara Maciel Braga,&nbsp;Carlos Gilbert Conte Filho,&nbsp;Fabio Batista Mota","doi":"10.1177/26330040221100840","DOIUrl":"10.1177/26330040221100840","url":null,"abstract":"<p><strong>Introduction: </strong>Rare genetic diseases affect millions of people worldwide. Most of them are caused by defective genes that impair quality of life and can lead to premature death. As genetic therapies aim to fix or replace defective genes, they are considered the most promising treatment for rare genetic diseases. Yet, as these therapies are still under development, it is still unclear whether they will be successful in treating these diseases. This study aims to address this gap by assessing researchers' opinions on the future of genetic therapies for the treatment of rare genetic diseases.</p><p><strong>Methods: </strong>We conducted a global cross-sectional web-based survey of researchers who recently authored peer-reviewed articles related to rare genetic diseases.</p><p><strong>Results: </strong>We assessed the opinions of 1430 researchers with high and good knowledge about genetic therapies for the treatment of rare genetic diseases. Overall, the respondents believed that genetic therapies would be the standard of care for rare genetic diseases before 2036, leading to cures after this period. CRISPR-Cas9 was considered the most likely approach to fixing or replacing defective genes in the next 15 years. The respondents with good knowledge believed that genetic therapies would only have long-lasting effects after 2036, while those with high knowledge were divided on this issue. The respondents with good knowledge on the subject believed that non-viral vectors are more likely to be successful in fixing or replacing defective genes in the next 15 years, while most of the respondents with high knowledge believed viral vectors would be more successful.</p><p><strong>Conclusion: </strong>Overall, the researchers who participated in this study expect that in the future genetic therapies will greatly benefit the treatment of patients with rare genetic diseases.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221100840"},"PeriodicalIF":0.0,"publicationDate":"2022-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/32/99/10.1177_26330040221100840.PMC10032453.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mannose treatment improves immune deficiency in mannose phosphate isomerase-congenital disorder of glycosylation: case report and review of literature.","authors":"Diederik De Graef,&nbsp;Jehan Mousa,&nbsp;Marta Biderman Waberski,&nbsp;Eva Morava","doi":"10.1177/26330040221091283","DOIUrl":"10.1177/26330040221091283","url":null,"abstract":"<p><p>Mannose phosphate isomerase-congenital disorder of glycosylation (MPI-CDG) is a CDG presenting with a clinically recognizable presentation, including early hypoglycemia, coagulation defects, and gastrointestinal and hepatic symptoms. We report on a female patient with biallelic pathogenic mutations in the <i>MPI</i> gene who presented with recurrent respiratory infections and abnormal IgM levels, but none of the classic symptoms associated with MPI-CDG. Oral mannose therapy led to a fast improvement in serum IgM levels and transferrin glycosylation in our patient. The patient did not experience severe infections after the initiation of treatment. We also reviewed the immune phenotype in patients so far reported with MPI-CDG.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221091283"},"PeriodicalIF":0.0,"publicationDate":"2022-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/42/f4/10.1177_26330040221091283.PMC10032425.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10662705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacology update: pamidronate for hypertrophic pulmonary osteoarthropathy in palliative care.","authors":"Bethany Faust,&nbsp;Aaron Parkinson,&nbsp;Steven J Baumrucker","doi":"10.1177/26330040211070298","DOIUrl":"10.1177/26330040211070298","url":null,"abstract":"<p><p>Hypertrophic pulmonary osteoarthropathy (HPOA) is a rare syndrome that causes clubbed fingers, periostitis, and synovial effusions. It can adversely impact a patient's quality of life. It occurs secondary to pulmonary disease - most commonly pulmonary malignancy. The most effective treatment for HPOA is to treat the underlying disease, usually through surgical resection, chemotherapy, or radiation. However, symptomatic treatments rather than definitive treatments (surgical, chemotherapy, or radiation) are more appropriate for the palliative care patient. Pamidronate is a promising medication for the treatment of HPOA for its safety and rapid onset of action. Further research is indicated to determine whether pamidronate is consistently effective.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040211070298"},"PeriodicalIF":0.0,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/ec/50/10.1177_26330040211070298.PMC10032426.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telehealth for patients with rare epilepsies.","authors":"Zachary J Kramer,&nbsp;Carrin Brandt,&nbsp;Kathryn Havens,&nbsp;Archana Pasupuleti,&nbsp;William D Gaillard,&nbsp;John M Schreiber","doi":"10.1177/26330040221076861","DOIUrl":"10.1177/26330040221076861","url":null,"abstract":"<p><p>Recent developments in technology and exigencies of the COVID-19 pandemic have spurred innovations for telehealth in patients with rare epilepsies. This review details the many ways telehealth may be used in the diagnosis and management of rare, pharmacoresistant epilepsy and documents our experience as measured by surveying caregivers of pediatric patients with epilepsy. Most components of the epilepsy evaluation, including history and examination, neuroimaging, and electroencephalogram (EEG) can be performed or reviewed remotely, assuming similar technique and quality of diagnostic studies. Seizure and epilepsy diagnosis is enhanced through the assistance of caregiver smart phone video recordings and 'ambulatory' EEG. Monitoring patient seizure frequency through paper seizure diaries is now increasingly being replaced by electronic diaries in both clinical and research settings. Electronic seizure diaries have numerous advantages such as data durability, increased accessibility, real-time availability, and easier analysis. Telehealth enhances access to specialized epilepsy care, which has been shown to reduce mortality and improve patient compliance and outcomes. Telehealth can also enable evaluation of patients with rare epilepsy in centers of excellence and enhance enrollment in clinical trials. Reducing mortality risk in patients with epilepsy can be accomplished through remote counseling and addressing psychiatric co-morbidities. Findings from surveying caregivers of children with epilepsy treated at Children's National Hospital showed that 54/56 (96.4%) found that not having to commute to the appointment positively contributed to their telemedicine experience. Overall, most respondents had a positive experience with their telemedicine visit. Almost all respondents (98%) were either 'very happy' or 'happy' with their telemedicine visit and their ability to communicate over telemedicine with the provider and either 'very likely' or 'likely' to want to use telemedicine for some future clinic visits. Telehealth in rare epilepsies is feasible and, in many ways, comparable with traditional evaluation and management.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221076861"},"PeriodicalIF":0.0,"publicationDate":"2022-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/0e/60/10.1177_26330040221076861.PMC10032469.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review investigating the Effectiveness of Exercise training in Glycogen Storage Diseases.","authors":"Claire Bordoli,&nbsp;Elaine Murphy,&nbsp;Ian Varley,&nbsp;Graham Sharpe,&nbsp;Philip Hennis","doi":"10.1177/26330040221076497","DOIUrl":"10.1177/26330040221076497","url":null,"abstract":"<p><strong>Introduction: </strong>Glycogen storage diseases (GSDs) are rare inborn errors of carbohydrate metabolism typically with skeletal muscle and liver involvement. In those with skeletal muscle involvement, the majority display symptoms of exercise intolerance which can cause profound exercise limitation and impair everyday living and quality of life (QoL). There are no curative treatments for GSDs, thus therapeutic options, such as exercise training, are aimed at improving QoL by alleviating signs and symptoms. In order to investigate the effectiveness of exercise training in adults with GSDs, we systematically reviewed the literature.</p><p><strong>Methods: </strong>In this review we conducted searches within SCOPUS and MEDLINE to identify potential papers for inclusion. These papers were independently assessed for inclusion and quality by two authors. We identified 23 studies which included aerobic training, strength training or respiratory muscle training in patients with McArdles (<i>n</i> = 41) and Pompe disease (<i>n</i> = 139).</p><p><strong>Results: </strong>In McArdle disease, aerobic exercise training improved aerobic capacity (VO₂ peak) by 14-111% with further benefits to functional capacity and well-being. Meanwhile, strength training increased muscle peak power by 100-151% and reduced disease severity. In Pompe disease, a combination of aerobic and strength training improved VO₂ peak by 9-10%, muscle peak power by 64%, functional capacity and well-being. Furthermore, respiratory muscle training (RMT) improved respiratory muscular strength [maximum inspiratory pressure (MIP) increased by up to 65% and maximum expiratory pressure (MEP) by up to 70%], with additional benefits shown in aerobic capacity, functional capacity and well-being.</p><p><strong>Conclusion: </strong>This adds to the growing body of evidence which suggests that supervised exercise training is safe and effective in improving aerobic capacity and muscle function in adults with McArdle or Pompe disease. However, the literature base is limited in quality and quantity with a dearth of literature regarding exercise training in other GSD subtypes.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221076497"},"PeriodicalIF":0.0,"publicationDate":"2022-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10032442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9469867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"What are the benefits of the anti-FGF23 antibody burosumab on the manifestations of X-linked hypophosphatemia in adults in comparison with conventional therapy? A review.","authors":"Marie-Hélène Lafage-Proust","doi":"10.1177/26330040221074702","DOIUrl":"10.1177/26330040221074702","url":null,"abstract":"<p><p>X-linked hypophosphatemia (XLH) is a genetic disease mostly related to PHEX gene mutations which increases FGF23 serum levels, leading to hypophosphatemia and osteomalacia in adults, while affected children, in addition, develop rickets. Most of adults with XLH suffer from reduced quality of life and physical disability due to chronic bone and joint pain related to limb deformities, early osteoarthritis, delayed-healing of insufficiency fractures, and enthesopathies. Dental infections, muscle dysfunction, and deafness are also frequent. The current treatment consists of 2-5 times daily oral administration of phosphate combined to active vitamin D, often badly tolerated with immediate digestive side effects, responsible for poor compliance. In the long term, it may induce nephrocalcinosis and hyperparathyroidism. Burosumab, an anti-FGF23 blocking antibody, was approved for treating children with XLH in many countries. A randomized 24-week-long placebo-controlled trial, followed by an open-label period of equal duration was conducted in 134 XLH adults treated with 1 mg/kg burosumab/4 weeks. During burosumab treatment, 94% of the patients normalized serum phosphate values <i>versus</i> 7% in the placebo group. Fracture healing was increased 16.7 times compared with placebo-treated patients. All pain and disability tests improved significantly in a time-dependent manner. Burosumab for 48 weeks improved histological lesions of osteomalacia in a single-arm longitudinal study analyzing paired bone biopsies. Another single-arm, open-label study investigated the long-term safety and efficacy of burosumab in 20 adult patients followed for 3.2 years. Burosumab was beneficial on pain and disability scores and on bone remodeling markers. No major side effects especially no hyperphosphatemic episodes were reported. Overall, the benefit/risk ratio of burosumab is positive in adult patients with clinical and/or biological complications of XLH. Burosumab corrects hypophosphatemia, promotes fracture healing, and induces a modest but significant effect on XLH-induced subjective pain and disability symptoms.</p><p><strong>Plain language title and summary: </strong><i>Effects of conventional treatment and burosumab in adults with X-linked hypophosphatemia</i>.X-linked hypophosphatemia (XLH) is a disease of genetic origin that affects mineralized tissues (skeleton and teeth) and impairs muscle function. It induces a decrease in blood phosphate levels. This leads to under mineralization of bones and insufficiency fractures that heal slowly, associated with poor dental health characterized by spontaneous dental abscesses. Adults with XLH suffer from chronic pain and limb deformities that alter their quality of life. They are currently treated with daily administration of vitamin D and several daily doses of phosphate. This treatment may induce parathyroid gland dysfunction and mineral deposits in the kidney. If not tightly monitored, these side effects may lead to","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221074702"},"PeriodicalIF":0.0,"publicationDate":"2022-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/70/70/10.1177_26330040221074702.PMC10032432.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9522681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic angiogenesis in Buerger's disease: reviewing the treatment landscape.","authors":"Antoine J Ribieras, Yulexi Y Ortiz, Zhao-Jun Liu, Omaida C Velazquez","doi":"10.1177/26330040211070295","DOIUrl":"10.1177/26330040211070295","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Thromboangiitis obliterans, also known as Buerger's disease, is a rare inflammatory vasculitis that predominantly develops in smokers and characteristically affects the small- and medium-sized peripheral arteries and veins. Patients typically present with extremity claudication, but symptoms may progress to rest pain and tissue loss, especially in those unable to abstain from tobacco use. Unfortunately, traditional medical treatments are largely ineffective and due to the small caliber of affected vessels and lack of suitable distal targets or venous conduits, endovascular and open surgical approaches are often not possible. Eventually, a significant number of patients require major amputation. For these reasons, much research effort has been made in developing techniques of therapeutic angiogenesis to improve limb perfusion, both for atherosclerotic peripheral arterial disease and the smaller subset of patients with critical limb ischemia due to Buerger's disease. Neovascularization in response to ischemia relies on a complex interplay between the local tissue microenvironment and circulating stem and progenitor cells. To date, studies of therapeutic angiogenesis have therefore focused on exploiting known angiogenic factors and stem cells to induce neovascularization in ischemic tissues. This review summarizes the available clinical data regarding the safety and efficacy of various angiogenic therapies, notably injection of naked DNA plasmids, viral gene constructs, and cell-based preparations, and describes techniques for potentiating &lt;i&gt;in vivo&lt;/i&gt; efficacy of gene- and cell-based therapies as well as ongoing developments in exosome-based cell-free approaches for therapeutic angiogenesis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Plain language title and summary: &lt;/strong&gt;&lt;i&gt;A review of available and emerging treatments for improving blood flow and wound healing in patients with Buerger's disease, a rare disorder of blood vessels&lt;/i&gt; Buerger's disease is a rare disorder of the small- and medium-sized blood vessels in the arms and legs that almost exclusively develops in young smokers. Buerger's disease causes inflammation in arteries and veins, which leads to blockage of these vessels and reduces blood flow to and from the extremities. Decreased blood flow to the arms and legs can lead to development of nonhealing wounds and infection for which some patients may eventually require amputation. Unfortunately, traditional medical and surgical treatments are not effective in Buerger's disease, so other methods for improving blood flow are needed for these patients. There are several different ways to stimulate new blood vessel formation, both in humans and animal models. The most common treatments involve injection of DNA or viruses that express genes related to blood vessel formation or, alternatively, stem cell-based treatments that help regenerate blood vessels and repair wound tissue. This review explores how safe and effective these various treatments are and desc","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040211070295"},"PeriodicalIF":0.0,"publicationDate":"2022-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/7a/81/10.1177_26330040211070295.PMC10032470.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9472955","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of the Covid-19 epidemic on a US sample of patients with myasthenia gravis.","authors":"Gloria Gutierrez,&nbsp;Helen Girma,&nbsp;Pierce Kuhnell,&nbsp;Maurizio Macaluso,&nbsp;Henry J Kaminski","doi":"10.1177/26330040221082673","DOIUrl":"https://doi.org/10.1177/26330040221082673","url":null,"abstract":"<p><strong>Introduction: </strong>The Covid-19 pandemic has devastated the world and demonstrated the inadequacy of health care in the United States. To assess its impact, the Rare Disease Clinical Research Network conducted a survey to assess the pandemic on the rare disease community of patients, including those with myasthenia gravis (MG).</p><p><strong>Methods: </strong>A cross-sectional survey was designed to target people or their care givers who live in the United States, have a rare disease, and are under 90 years of age. Respondents logged onto a dedicated web page and completed the survey online, which requested demographic, disease-specific, drug treatment, and symptom information as well as assessment of Covid-19 impact on them. The survey was open from May 2020 to December 2020.</p><p><strong>Results: </strong>Five hundred ninety-four with self-reported myasthenia gravis completed the survey, which was the largest number of respondents. Sixty percent of respondents were women with a mean age of 60 years. Eighty-nine percent identified as White. Respondents did not appreciate a worsening of symptoms after the pandemic. Only 7 respondents reported the diagnosis of Covid-19 but 11% indicated they had difficulty accessing care at the time of the survey.</p><p><strong>Discussion and conclusion: </strong>Patients with MG complained of worse access to medical care during the early months of the pandemic, including challenges in diagnosis of suspected Covid-19 infection. A major limitation of the survey is its inability to access minority populations. Nevertheless, the results of the Rare Disease Clinical Research Network (RCDRN) survey of patients with MG provide clear evidence that the pandemic has demonstrated the deficiencies in US healthcare.</p>","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"3 ","pages":"26330040221082673"},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/3e/79/10.1177_26330040221082673.PMC10032427.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9399548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond pigmentation: signs of liver protection during afamelanotide treatment in Swiss patients with erythropoietic protoporphyria, an observational study.","authors":"Anna-Elisabeth Minder,&nbsp;Jasmin Barman-Aksoezen,&nbsp;Mathias Schmid,&nbsp;Elisabeth I Minder,&nbsp;Henryk Zulewski,&nbsp;Christoph E Minder,&nbsp;Xiaoye Schneider-Yin","doi":"10.1177/26330040211065453","DOIUrl":"10.1177/26330040211065453","url":null,"abstract":"<p><p>Erythropoietic protoporphyria (EPP) is an ultra-rare inherited disorder with overproduction of protoporphyrin in maturating erythroblasts. This excess protoporphyrin leads to incapacitating phototoxic burns in sunlight exposed skin. Its biliary elimination causes cholestatic liver injury in 20% and terminal liver failure in 4% of EPP patients. Thereby, the risk of liver injury increases with increasing erythrocyte protoporphyrin concentrations. Afamelanotide, an α-melanocyte-stimulating hormone (MSH) analog inducing skin pigmentation, was shown to improve sunlight tolerance in EPP. Beyond this well-known effect on pigmentation, the MSHs have liver-protective effects and improve survival of maturating erythroblasts, effects described in animal or <i>in vitro</i> models to date only. We investigated whether afamelanotide treatment in EPP has effects on erythropoiesis, protoporphyrin concentrations, and liver injury by analyzing retrospectively our long-term safety data.</p><p><strong>Methods: </strong>From the 47 Swiss EPP-patients treated at our center since 2006, we included those 38 patients in the current analysis who received at least one afamelanotide dose between 2016 and 2018 and underwent regular laboratory testing before and during the treatment. We compared the means of pretreatment measurements with those during the treatment.</p><p><strong>Results: </strong>Protoporphyrin concentrations dropped from 21.39 ± 11.12 (mean ± SD) before afamelanotide to 16.83 ± 8.24 µmol/L (<i>p</i> < .0001) during treatment. Aspartate aminotransferase decreased from 26.67 ± 13.16 to 22.9 ± 7.76 IU/L (<i>p</i> = .0146). For both entities, patients with higher values showed a more progressive decrease, indicating a risk reduction of EPP-related liver disease. The pre-existing hypochromia and broad mean red-cell distribution width were further augmented under afamelanotide. This was more likely due to an influence of afamelanotide on maturating erythroblasts than due to an exacerbated iron deficiency, as mean zinc-protoporphyrin decreased significantly and ferritin remained unchanged. No serious afamelanotide-related adverse events were observed for a total of 240 treatment years.</p><p><strong>Conclusion: </strong>Our findings point to a protective effect of afamelanotide on erythroblast maturation and protoporphyrin-induced liver injury.</p><p><strong>Plain language summary: </strong><b>Afamelanotide, a skin tanning hormone, may protect patients with erythropoietic protoporphyria not only from skin burns, but also from liver injury associated with the disease.</b> Patients with erythropoietic protoporphyria (EPP), an inherited metabolic disease, suffer from light-induced skin burns and liver injury elicited by the accumulated light sensitizer protoporphyrin. The excess protoporphyrin is produced in red cell precursors in the bone marrow, and it is eliminated from the body <i>via</i> the liver and bile. A high protoporphyrin excretion burden damages th","PeriodicalId":75218,"journal":{"name":"Therapeutic advances in rare disease","volume":"2 ","pages":"26330040211065453"},"PeriodicalIF":0.0,"publicationDate":"2021-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/e4/ca/10.1177_26330040211065453.PMC10032460.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10299665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}