Orphanet Journal of Rare Diseases最新文献

{"title":"Introducing a revised version of the Kumamoto scale as an easy-to-use clinical tool for monitoring multisystemic changes in hereditary transthyretin amyloidosis.","authors":"Jonas Wixner, Björn Pilebro, Tale N Wien, Per Eldhagen, Henning Mölgaard, Björn Hedström, Astrid J Terkelsen","doi":"10.1186/s13023-025-03915-w","DOIUrl":"10.1186/s13023-025-03915-w","url":null,"abstract":"<p><strong>Background: </strong>Hereditary transthyretin (ATTRv) amyloidosis is a rare but life-threatening multisystemic disease. Multiple disease-modifying treatments are now available and standardised instruments for early detection and disease monitoring are essential. Still, validated and easy-to-use tools for clinical follow-up are scarce.</p><p><strong>Methods: </strong>The Kumamoto scale was first described in 1997 as a method for systematically evaluating patients with ATTRv amyloidosis and has been used in clinical trials since. A panel of amyloidosis experts from Sweden, Denmark, and Norway discussed the strengths and limitations of the Kumamoto scale at the Nordic Amyloidosis Day at Arlanda in 2023, and it was decided to revise and improve the scale that has been used in routine clinical monitoring of patients in Sweden since 2020. Our aim is to introduce the revised version of the Kumamoto scale as a useful clinical monitoring tool.</p><p><strong>Results: </strong>Minor adjustments were applied to make the scale more sensitive and precise. Bedside instruments for sensory examination were defined as well as the sensory and motor levels. Constipation was added as a sign of autonomic dysfunction. The subtotal and total scores remain unchanged.</p><p><strong>Conclusions: </strong>We believe that the revised Kumamoto scale is a reliable and easy-to-use clinical tool for monitoring ATTRv amyloidosis.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"377"},"PeriodicalIF":3.5,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297637/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144718272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The burden of illness in Prader-Willi syndrome: a systematic literature review.","authors":"Dairine Dempsey, Maria Hall, Ben Lanning, Ben Barron-Millar, Michael Huang, Neil Cowen, Mitch Nagao, Raj Gandhi, Anish Bhatnagar","doi":"10.1186/s13023-025-03787-0","DOIUrl":"10.1186/s13023-025-03787-0","url":null,"abstract":"<p><strong>Background: </strong>Prader-Willi syndrome (PWS) is a rare, genetic neurobehavioral and metabolic disorder marked by hyperphagia, behavioral challenges, and significant comorbidities, requiring a multidisciplinary approach for effective management. This systematic review aimed to comprehensively evaluate the burden of disease associated with PWS, focusing on mortality, healthcare resource utilization, economic burden, and quality of life.</p><p><strong>Methods: </strong>The literature search, conducted on August 13, 2024, included the MEDLINE, Embase, and Cochrane Library databases, as well as conference proceedings. Original studies published since 2014 were selected based on relevance to PWS patient burden, covering mortality, humanistic and economic impacts. Data from the selected studies were extracted, and currency conversions were standardized.</p><p><strong>Results: </strong>For the topics of mortality, humanistic burden and economic burden, a total of 11 studies, 95 studies, and 33 studies were included, respectively. Individuals with PWS faced significantly reduced life expectancy compared to the general population, with leading causes of death including respiratory failure, consequences of uncontrolled hyperphagia, and cardiovascular complications. Hyperphagia contributed substantially to the disease burden, necessitating constant food security measures to prevent life-threatening complications. Primary caregivers, predominantly parents of individuals with PWS, experienced significant emotional and psychological strain. The time-intensive responsibilities of implementing food security measures heavily impacted their daily lives, social and family dynamics, as well as their financial health. Quality of life for patients was less frequently reported but markedly impaired, driven by physical health challenges, behavioral issues, and social isolation. Wider family dynamics were also often impacted, with siblings reporting increased psychosocial stress and feelings of neglect. The direct costs of managing PWS, including frequent hospitalizations and specialized care, were consistently reported to exceed those of matched controls without PWS, highlighting the substantial economic burden associated with the condition.</p><p><strong>Conclusion: </strong>This systematic literature review highlights the profound burden of PWS on patients, caregivers, payers of care, and healthcare systems. Complications of PWS reduce life expectancy, impair quality of life, and impose considerable financial strain. The findings underscore an urgent need for comprehensive support and innovative treatments that address the complex manifestations and consequences of PWS, particularly hyperphagia, to improve outcomes for patients and their families.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"374"},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12291511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708404","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japanese experience of newborn screening for lysosomal storage diseases and adrenoleukodystrophy.","authors":"Takanori Onuki, Makiko Tajika, Yohei Sugiyama, Masaru Shimura, Keiko Ichimoto, Toju Tanaka, Hiromi Nyuzuki, Motomichi Kosuga, Ohsuke Migita, Tetsuya Ito, Hideo Sasai, Ryosuke Bo, Junpei Hamada, Takashi Hamazaki, Norio Sakai, Takahito Inoue, Kimitoshi Nakamura, Torayuki Okuyama, Kei Murayama","doi":"10.1186/s13023-025-03848-4","DOIUrl":"10.1186/s13023-025-03848-4","url":null,"abstract":"<p><strong>Background: </strong>Recently, Newborn screening (NBS) has been expanded worldwide to include lysosomal storage diseases (LSDs) and adrenoleukodystrophy (ALD) due to the importance of early diagnosis and early treatment. In Japan, NBS for LSDs, termed expanded NBS, was first implemented in Kumamoto prefecture in 2006 as pilot study. NBS for ALD was subsequently introduced in Aichi prefecture and Gifu prefecture in 2021. Expanded NBS for LSDs and ALD has become more widespread in Japan. In light of this current situation, we considered it is necessary to clarify the usefulness of expanded NBS, prevalence of each disease, challenges encountered. Therefore, we reported the current implementation status of expanded NBS in Japan.</p><p><strong>Method: </strong>A survey was conducted among physicians responsible for expanded NBS in each target region Japan. The target regions were those that implemented NBS for LSDs and/or ALD for more than one year. The survey items included: the entity conducting expanded NBS, the facilities conducting the tests, the target areas, medical institutions for close examination such as detailed biochemical analysis and/or genetic sequencing, and treatments, types of target diseases, fee for NBS, sample collection methods, testing method, and quantitative data on expanded NBS, retesting, and diagnoses in each area.</p><p><strong>Results: </strong>Responses were received from nine regions and an organization (CReARID). The total number of 733,838 newborns were screening, with 101 diagnoses: 75 cases of Fabry disease, 10 of mucopolysaccharidosis (MPS) II, 8 of Pompe disease, 5 of Gaucher disease, 2 of MPS I, 1 of ALD, respectively) were diagnosed. More cases were diagnosed with the target disease than the estimated prevalence. In contrast, the positive predictive value was low and false-positive rates was elevated, particularly for PD, MPS II, and ALD, have been attributed to pseudodeficiency alleles and methodological differences. Moreover, variant of unknown significance (VUS) in the ABCD1 gene was detected in many of the patients with suspected ALD.</p><p><strong>Conclusion: </strong>In Japan, Expanded NBS for LSDs and ALD has become more widespread. Since its implementation, some patients have been diagnosed and received treatment. However, challenges such as pseudodeficiency, indications, testing methods, and VUS that require improvement.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"373"},"PeriodicalIF":3.5,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12288336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144708403","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First 100 patients receiving long-acting growth hormone therapy: real-world evaluation from INSIGHTS-GHT registry.","authors":"Joachim Woelfle, I Kreitschmann-Andermahr, C J Strasburger, D B Pittrow, C Pausch, D Schnabel","doi":"10.1186/s13023-025-03898-8","DOIUrl":"10.1186/s13023-025-03898-8","url":null,"abstract":"<p><p>The development of long-acting growth hormone (LAGH) formulations offers a promising approach to reduce injection frequency and to improve adherence in growth hormone deficiency (GHD) treatment. INSIGHTS-GHT is the first product-independent registry to document the real-world use of recombinant human (rh) growth hormone (GH) replacement therapy within the labelling. Following the market launch of three LAGH products in Germany (lonapegsomatropin, somapacitan, and somatrogon) we aimed to provide early real-world evidence on their use in order to obtain an initial picture on patient selection and physician preferences outside of clinical trials.We report in this interim analysis on 70 pediatric patients from 15 centers across Germany as well as 31 adult patients from 6 German centers under LAGH treatment. The majority of the pediatric patients (76%) were male, with a mean age at LAGH initiation of 9.2 years. About half of the pediatric patients (54%) were switch patients transitioning from daily GH therapy. Notably, 82% of patients received a LAGH starting dose below the manufacturer's recommendation, with a median dose of 92% of the recommended level. In the group of adult patients, 65% were male, with a mean age of 38.2 years at LAGH initiation. In pediatric patients, before start of GH therapy, mean IGF-I (SDS) was - 2.1 ± 1.1 SDS, mean IGFBP-3 (SDS) was - 2.0 ± 1.5 SDS.All adult patients switched from daily GH therapy. More than half (55%) received the LAGH starting dose according to the manufacturer's recommendation, while 41% began with a lower-than-recommended dose. Our findings provide early insights into LAGH therapy adoption and highlight the need for continued follow-up to evaluate long-term efficacy, adherence, and safety in real-world settings.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"372"},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285006/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"\"It's like nursing a butterfly-so delicate, difficult, and unpredictable\" - challenges of nurses in caring for patients with epidermolysis bullosa: a qualitative study.","authors":"Parivash Karimi, Moloud Radfar, Yaser Moradi","doi":"10.1186/s13023-025-03925-8","DOIUrl":"10.1186/s13023-025-03925-8","url":null,"abstract":"<p><strong>Background: </strong>Patients with Epidermolysis Bullosa (EB) face extensive and complex challenges, and nurses play a decisive role in providing care for them and educating their families. However, the multifaceted nature of EB care introduces significant challenges for nurses.</p><p><strong>Objective: </strong>This study aimed to explore the challenges nurses face in caring for patients with EB.</p><p><strong>Methods: </strong>This is a qualitative study conducted from August to December 2024. Semi-structured, in-depth, face-to-face interviews were conducted with 15 nurses who provided care to patients with EB in Urmia, Northwest Iran. Data were analyzed using the conventional content analysis approach proposed by Graneheim and Lundman (2004).</p><p><strong>Results: </strong>Data analysis revealed three main categories of challenges faced by nurses in caring for patients with EB: \"Problematic Parental Reactions\" which includes harmful parental demands, difficult initial encounters, and parental detachment; \"Care Avoidance\" encompassing arduous routine care and the psycho-erosive nature of care; and \"The Forgotten Illness\" characterized by limited organizational support and insufficient organizational knowledge enhancement.</p><p><strong>Conclusion: </strong>Caring for EB patients presents numerous challenges for nurses, including Problematic Parental Reactions, care avoidance, and the broader context of a forgotten illness. Parental demands, difficult initial encounters, and parental detachment complicate the care, while the demanding and psycho-erosive nature of daily tasks exacerbates nurse fatigue. Furthermore, organizational neglect-stemming from inadequate resources and insufficient training-intensifies these difficulties. These findings highlight the need for targeted training programs and systemic support to address the unique difficulties inherent in caring for patients with EB.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"371"},"PeriodicalIF":3.5,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12285049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144699196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silver-Russell syndrome: phenotype features and oral health status.","authors":"Paula Piekoszewska-Ziętek, Aneta Witt-Porczyk, Krystyna Chrzanowska, Małgorzata Zadurska, Dorota Olczak Kowalczyk","doi":"10.1186/s13023-025-03886-y","DOIUrl":"10.1186/s13023-025-03886-y","url":null,"abstract":"<p><strong>Background: </strong>Silver-Russell Syndrome is a rare malformation syndrome with a variable clinical and genetic presentation. Its incidence is estimated at 1:70.000-1:100.000 births. Since the diagnosis of Silver-Russell syndrome is based primarily on the identification of clinical features, studies assessing the craniofacial/dental changes present in this group of patients are important. The aim of the study was to evaluate phenotype features and oral health status in patients with Silver-Russell syndrome.</p><p><strong>Results: </strong>In the extraoral examination, patients with SRS were found to have a triangular facial shape, facial asymmetry, low-set, protruding ears, narrow lips and downward-facing mouth angles. In intraoral examination, reduced tongue dimensions, cleft palate and gothic palate were observed. There were no statistically significant differences in Plaque Index values between the groups. Gingival Index values were significantly higher in the Silver-Russell syndrome. The prevalence of caries was also higher in the group of subjects with Silver-Russell syndrome.</p><p><strong>Conclusions: </strong>Patients with Silver-Russell syndrome present themselves with features that affect oral health. Prompt orthodontic and dental intervention in children with SRS can help normalize oral function and facial appearance.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"370"},"PeriodicalIF":3.4,"publicationDate":"2025-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12276679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144668079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vivo applications and toxicities of AAV-based gene therapies in rare diseases.","authors":"Qian Zhao, Huifang Peng, Yujin Ma, Huijun Yuan, Hongwei Jiang","doi":"10.1186/s13023-025-03893-z","DOIUrl":"10.1186/s13023-025-03893-z","url":null,"abstract":"<p><p>Adeno-associated virus (AAV), renowned for its exceptionally low pathogenicity and significant efficacy in clinical gene therapy, has emerged as a leading delivery vector in the field of gene therapy. AAV can achieve stable gene expression in various tissues, which has made it a promising treatment for genetic disorders. To date, eight AAV-based gene therapies have been approved by the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA). This review summarizes clinical trials of AAV gene therapies for rare diseases, including ophthalmic diseases, nervous system disorders, hematological diseases, neuromuscular diseases, lysosomal storage diseases. We also explore potential side effects and toxicities associated with AAV therapies. Our objective is to provide valuable insights for researchers and clinicians working on AAV-based therapies, helping improve the safety and effectiveness of these treatments.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"368"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272985/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating vosoritide therapy with limb surgery in paediatric patients with achondroplasia: real-life experiences.","authors":"Anna Elsa Maria Allegri, Maria Francesca Bedeschi, Maria Beatrice Bocchi, Valentina Camurri, Michaela Veronika Gonfiantini, Chiara Leoni, Milena Mariani, Osvaldo Palmacci, Matteo Porro, Simone Riganti, Caterina Tedesco, Berardo Rinaldi, Emanuela Scarano, Concetta Schiavariello, Angelo Selicorni, Stefano Stagi, Fabio Verdoni, Giuseppe Zampino, Mohamad Maghnie, Roberta Onesimo","doi":"10.1186/s13023-025-03853-7","DOIUrl":"10.1186/s13023-025-03853-7","url":null,"abstract":"<p><strong>Background: </strong>Achondroplasia is the most common form of disproportionate short stature and can lead to serious medical complications, including foramen magnum and spinal stenosis. Until 2021, there were no precision treatments available, and in some countries, elective surgery was considered a standard approach to increase height, improve body proportions, enhance functionality, and correct deformities in a selected group of patients. Recently, C-type natriuretic peptide (CNP) has been explored as a potential treatment, aiming to counteract the molecular activity driven by FGFR3. Although post-market and real-world data on the drug are still limited, many questions remain about the potential for combining pharmacological and surgical therapies and how this might influence patient outcomes. Concerns have also been raised regarding the potential impact of drugs on bone healing. However, anecdotal evidence from orthopaedic practice suggests that the two ossification processes do not interfere with one another. The aim of this study was to describe the first real-world case series in which vosoritide treatment was integrated with limb surgery in children and adolescents with achondroplasia.</p><p><strong>Results: </strong>Sixteen paediatric patients with molecular confirmation of achondroplasia were included in the study. All patients underwent combined vosoritide therapy and limb surgeries (13 for lower limb lengthening and 3 for varus correction through epiphysiodesis).The complementary roles of vosoritide therapy and surgery were highlighted, with treatment outcomes aligning closely with expectations.</p><p><strong>Conclusion: </strong>This report provides the first clinical description of the combination of precision therapy with limb surgery in a relatively large multicentre cohort of paediatric patients with achondroplasia. These findings support continued exploration of the integration of different therapeutic approaches.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"369"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12273278/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659775","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Musculoskeletal deformities of Alström syndrome-a review of 55 cases.","authors":"Subadra Wanninayake, Richard Paisey, Hitesh Dabasia, Ashley Cole, Charlotte Dawson, Tarekegn Hiwot","doi":"10.1186/s13023-025-03867-1","DOIUrl":"10.1186/s13023-025-03867-1","url":null,"abstract":"<p><strong>Introduction: </strong>Alström syndrome (ALMS) is an ultra-rare metabolic disorder caused by biallelic loss-of-function in the Alms1 gene which encodes a ubiquitously expressed centrosomal protein of the primary cilium. Dual sensory defects, several metabolic and hormonal dysfunctions are frequent in ALMS. Increased musculoskeletal deformities have been observed, though these aspects have not been systematically reviewed. This study characterises the anthropometric, clinical, genetic and imaging features of bone deformities in a large UK cohort with ALMS and describes the details of first documented successful corrective surgery for scoliosis.</p><p><strong>Methods: </strong>A preliminary study of 13 Alström patients was undertaken to evaluate musculoskeletal deformities. Written consent was obtained after sharing of study information via voice mail or Braille. Questionnaires, clinical examination and radiological evaluations were conducted twice 12 months apart by a rheumatologist and an orthopaedic surgeon. Two patients had scoliosis which required intervention. To discover its prevalence, 42 further AS patients were reviewed. All patients attended the Alstom syndrome UK specialist clinics.</p><p><strong>Results: </strong>In the detailed survey of 13 patients, all had some degree of musculoskeletal deformities, most commonly partially correctable thoracic kyphosis, brachydactyly, femoral anteversion and pes planus but rarely affecting their daily functioning. In the larger group of 55 patients, 6 had scoliosis requiring intervention; two of whom had spinal deformity requiring surgical correction in adolescence, and one had cervical spine surgery for spondylitis.</p><p><strong>Conclusion: </strong>ALMS patients tend to have high prevalence of musculoskeletal deformities which may be part of the ciliopathy. Postural adaptation to dual sensory loss resulted in correctable kyphosis, treatable by physiotherapy. Scoliosis requiring intervention is frequent (10.9%), with successful surgery undertaken where indicated.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"367"},"PeriodicalIF":3.4,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12272957/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144659776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A father's crusade in rare disease drug development: a case study of Elpida therapeutics and Melpida.","authors":"Deanna Portero, Qingyang Xu, Aaliya Hussain, Andrew W Lo","doi":"10.1186/s13023-025-03892-0","DOIUrl":"10.1186/s13023-025-03892-0","url":null,"abstract":"<p><p>Therapeutic development for rare diseases is difficult for pharmaceutical companies due to significant scientific challenges, extensive costs, and low financial returns. It is increasingly common for caregivers and patient advocacy groups to partner with biomedical professionals to finance and develop treatments for rare diseases. This case study illustrates the story of Terry Pirovolakis, a father who partnered with biomedical professionals to develop the novel gene therapy, Melpida, within 36 months of the diagnosis of his infant son. We identify the factors that led to the success of Melpida and analyze the business model of Elpida Therapeutics, a social purpose corporation founded by Pirovolakis to reproduce the success of Melpida for other rare diseases. We conclude with four lessons from Melpida to inform caregivers like Pirovolakis on developing novel gene therapies to save their loved ones.</p>","PeriodicalId":19651,"journal":{"name":"Orphanet Journal of Rare Diseases","volume":"20 1","pages":"363"},"PeriodicalIF":3.4,"publicationDate":"2025-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12265280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144643128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}