scholarly journals Disease monitoring programs of rare genetic diseases: transparent data sharing between academic and commercial stakeholders

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Hanns Lochmüller ◽  
Antonio Nino Ramirez ◽  
Emil Kakkis
Keyword(s):  
Conflicts Of Interest ◽  
Genetic Diseases ◽  
Neuromuscular Diseases ◽  
Disease Monitoring ◽  
Concept Of Disease ◽  
Monitoring Programs ◽  
Rare Genetic Diseases ◽  
Post Marketing ◽  
Current Compliance

AbstractIt has recently been suggested that registries for rare neuromuscular diseases should be formed and governed exclusively by physicians and patients in an effort to limit conflicts of interest. Enacting such an approach would not only be challenging logistically and financially, but it would also exclude the involvement of sponsors, who are an integral component of drug development within the current compliance framework. Therefore, as an alternative to traditional registries, we propose the use of a better collaborative model for post-marketing follow-up that includes all stakeholders. We developed the concept of Disease Monitoring Programs (DMPs), which are designed to monitor disease manifestations over a 10-year period whether on a sponsored drug or not, and ensure consistent collection, ownership sharing and governance of data.

scholarly journals Targeted therapies for congenital myasthenic syndromes: systematic review and steps towards a treatabolome

2019 ◽  
Vol 3 (1) ◽  
pp. 19-37 ◽  
Author(s):  
Rachel Thompson ◽  
Gisèle Bonne ◽  
Paolo Missier ◽  
Hanns Lochmüller
Keyword(s):  
Systematic Review ◽  
Genetic Diseases ◽  
Genetic Defect ◽  
Genetic Diagnosis ◽  
Neuromuscular Diseases ◽  
Congenital Myasthenic Syndromes ◽  
Rare Genetic Diseases ◽  
Computer Aided ◽  
Receive Treatment ◽  
Myasthenic Syndromes

Abstract Despite recent scientific advances, most rare genetic diseases — including most neuromuscular diseases — do not currently have curative gene-based therapies available. However, in some cases, such as vitamin, cofactor or enzyme deficiencies, channelopathies and disorders of the neuromuscular junction, a confirmed genetic diagnosis provides guidance on treatment, with drugs available that may significantly alter the disease course, improve functional ability and extend life expectancy. Nevertheless, many treatable patients remain undiagnosed or do not receive treatment even after genetic diagnosis. The growth of computer-aided genetic analysis systems that enable clinicians to diagnose their undiagnosed patients has not yet been matched by genetics-based decision-support systems for treatment guidance. Generating a ‘treatabolome’ of treatable variants and the evidence for the treatment has the potential to increase treatment rates for treatable conditions. Here, we use the congenital myasthenic syndromes (CMS), a group of clinically and genetically heterogeneous but frequently treatable neuromuscular conditions, to illustrate the steps in the creation of a treatabolome for rare inherited diseases. We perform a systematic review of the evidence for pharmacological treatment of each CMS type, gathering evidence from 207 studies of over 1000 patients and stratifying by genetic defect, as treatment varies depending on the underlying cause. We assess the strength and quality of the evidence and create a dataset that provides the foundation for a computer-aided system to enable clinicians to gain easier access to information about treatable variants and the evidence they need to consider.

scholarly journals Considerations for Home-Based Treatment of Fabry Disease in Poland during the COVID-19 Pandemic and Beyond

2021 ◽  
Vol 18 (16) ◽  
pp. 8242
Author(s):  
Michał Nowicki ◽  
Stanisława Bazan-Socha ◽  
Mariusz Kłopotowski ◽  
Beata Błażejewska-Hyżorek ◽  
Mariusz Kusztal ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Genetic Diseases ◽  
Healthcare Providers ◽  
Treatment Programs ◽  
Current Therapy ◽  
Term Care ◽  
Pharmacological Chaperone ◽  
Enzyme Replacement ◽  
Home Based ◽  
Rare Genetic Diseases

Current therapy for Anderson–Fabry disease in Poland includes hospital or clinic-based intravenous enzyme replacement therapy with recombinant agalsidase alpha or beta, or oral pharmacological chaperone therapy with migalastat. Some countries around the world offer such treatment to patients in the comfort of their own homes. The 2020–2021 COVID-19 pandemic has pushed global healthcare providers to evolve their services so as to minimize the risk of COVID-19 exposure to both patients and providers; this has led to advances in telemedicine services and the increasing availability of at-home treatment for various procedures including parenteral drug administration. A total of 80% of surveyed Anderson–Fabry disease patients in Poland would prefer home-based treatment, which would be a safe and convenient alternative to clinic-based treatment if patient selection is based on our proposed algorithm. Our recommendations for home-based treatments appear feasible for the long term care of Anderson–Fabry disease patients during the COVID-19 pandemic and beyond. This may also serve as a basis for home-based treatment programs in other rare and ultra-rare genetic diseases.

scholarly journals TRIM32 and Malin in Neurological and Neuromuscular Rare Diseases

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 820
Author(s):  
Lorena Kumarasinghe ◽  
Lu Xiong ◽  
Maria Adelaida Garcia-Gimeno ◽  
Elisa Lazzari ◽  
Pascual Sanz ◽  
...  
Keyword(s):  
Common Ancestor ◽  
Genetic Diseases ◽  
Ubiquitin Ligases ◽  
E3 Ubiquitin Ligases ◽  
Lafora Disease ◽  
C Terminus ◽  
Rare Genetic Diseases ◽  
Tripartite Motif ◽  
Trim Proteins ◽  
Ring E3

Tripartite motif (TRIM) proteins are RING E3 ubiquitin ligases defined by a shared domain structure. Several of them are implicated in rare genetic diseases, and mutations in TRIM32 and TRIM-like malin are associated with Limb-Girdle Muscular Dystrophy R8 and Lafora disease, respectively. These two proteins are evolutionary related, share a common ancestor, and both display NHL repeats at their C-terminus. Here, we revmniew the function of these two related E3 ubiquitin ligases discussing their intrinsic and possible common pathophysiological pathways.

scholarly journals E-Health & Innovation to Overcome Barriers in Neuromuscular Diseases. Report from the 1st eNMD Congress: Nice, France, March 22-23, 2019

2021 ◽  
pp. 1-12
Author(s):  
Jonathan Pini ◽  
Gabriele Siciliano ◽  
Pauline Lahaut ◽  
Serge Braun ◽  
Sandrine Segovia-Kueny ◽  
...  
Keyword(s):  
Data Privacy ◽  
Neuromuscular Diseases ◽  
Disease Assessment ◽  
Private Companies ◽  
Social Burden ◽  
Database Construction ◽  
Significant Step ◽  
New Perspective ◽  
Expert Community

By definition, neuromuscular diseases are rare and fluctuating in terms of symptoms; patients are often lately diagnosed, do not have enough information to understand their condition and be proactive in their management. Usually, insufficient resources or services are available, leading to patients’ social burden. From a medical perspective, the rarity of such diseases leads to the unfamiliarity of the medical staff and caregiver and an absence of consensus in disease assessment, treatment, and management. Innovations have to be developed in response to patients’ and physicians’ unmet needs. It is vital to improve several aspects of patients’ quality of life with a better comprehension of their disease, simplify their management and follow-up, help their caregiver, and reduce the social and economic burden for living with a rare debilitating disease. Database construction regrouping patients’ data and symptoms according to specific country registration on data privacy will be critical in establishing a clear consensus on neuromuscular disease treatment. Clinicians also need technological innovations to help them recognize neuromuscular diseases, find the best therapeutic approach based on medical consensus, and tools to follow patients’ states regularly. Diagnosis also has to be improved by implementing automated systems to analyze a considerable amount of data, representing a significant step forward to accelerate the diagnosis and the patients’ follow up. Further, the development of new tools able to precisely measure specific outcomes reliably is of the matter of importance in clinical trials to assess the efficacy of a newly developed compound. In this context, the creation of an expert community is essential to communicate and share ideas. To this end, 97 clinicians, healthcare professionals, researchers, and representatives of private companies from 9 different countries met to discuss the new perspective and challenges to develop and implement innovative tools in the field of neuromuscular diseases. Keywords:

scholarly journals High-Throughput Sequencing and Rare Genetic Diseases

2012 ◽  
Vol 3 (5) ◽  
pp. 197-203 ◽  
Author(s):  
P. Makrythanasis ◽  
S.E. Antonarakis
Keyword(s):  
High Throughput ◽  
High Throughput Sequencing ◽  
Genetic Diseases ◽  
Rare Genetic Diseases

Burden of care in families of patients with rare genetic diseases: analysis of a large Italian cohort

2021 ◽  
pp. 104230
Author(s):  
Alex Moretti ◽  
Paola Cianci ◽  
Anita De Paoli ◽  
Francesca Meroni ◽  
Silvia Tajè ◽  
...  
Keyword(s):  
Genetic Diseases ◽  
Burden Of Care ◽  
Rare Genetic Diseases ◽  
Italian Cohort

Abstract 1122‐000142: Safety and Efficacy of Surpass Streamline for Intracranial Aneurysms: A Multicenter US Real‐World Experience (SESSIA)

2021 ◽  
Vol 1 (S1) ◽  
Author(s):  
Juan Vivanco‐Suarez ◽  
Alan Mendez‐Ruiz ◽  
Farooqui Mudassir ◽  
Cynthia B Zevallos ◽  
Milagros Galecio‐Castillo ◽  
...  
Keyword(s):  
Real World ◽  
Intracranial Aneurysms ◽  
The United States ◽  
Chromium Alloy ◽  
Cobalt Chromium ◽  
Anterior Circulation ◽  
Safety And Efficacy ◽  
Post Marketing ◽  
The Mean

Introduction : Flow diversion has established itself as standard treatment of wide complex intracranial aneurysms (IA). Its recognition has been validated with positive occlusion rates and favorable clinical outcomes. The Surpass Streamline (SS) flow diverter (FD) is a braided cobalt/chromium alloy implant with 72 or 96 wires approved by the FDA in 2018. The aim of this study is to determine the safety and efficacy of the SS in a post‐marketing large US cohort. Methods : We performed a multicenter, retrospective study for consecutive patients treated with the SS FD for IA between January 2018 and June 2021 in the United States. Inclusion criteria for participants were: 1. Adults (≥ 18 years) and 2. Treatment with SS FD for IA. Primary safety end point was a major ipsilateral stroke (increase in National Institutes of Health Stroke Scale Score of ≥ 4) or neurological death within 12 months. Primary efficacy was assessed using the 3‐point Raymond‐Roy (RR) occlusion scale on digital subtraction angiography (DSA) at 6‐12‐month follow‐up. Results : A total of 276 patients with 313 aneurysms were enrolled. The median age was 59 years and 199 (72%) were females. The most common comorbidities included hypertension in 156 (57%) subjects followed by hyperlipidemia in 76 (28%) patients. One hundred and twenty‐two (44%) patients were asymptomatic while subarachnoid hemorrhage was present in only 10 (4%) patients. A total of 143 (46%) aneurysms were left‐sided. Aneurysms were located as follows: 274 (88%) were in the anterior circulation with paraophthalmic being the most common in 120 (38%) followed by petrocavernous ICA in 81 (26%); 33 (11%) aneurysms were located in the posterior circulation with basilar trunk being the most common in 14 (5%). The mean maximum aneurysm dome width was 5.77 ± 4.7 mm, neck width 4.22 ± 3.8 mm and dome to neck ratio was 1.63 ± 1.3 mm. The mean number of SS FD implanted per aneurysm was 1.06 (range 1–3) with more than one SS FD implanted in 21 (7%) aneurysms. Modified Rankin Scale (mRS) of 0–2 was present in 206/213 (97%) patients at 6–12 month follow‐up. The complete aneurysm occlusion (RR 1) rate was 145/175 (83%) among subjects who had angiographic follow‐up at 6–12 months. Major stroke and death was encountered in 7 (2%) and 5 (1.8%) of the patients respectively. Conclusions : Our data represent the largest real‐world study using SS FD. These results corroborate its post‐marketing safety and efficacy for the treatment of intracranial aneurysms showing more favorable rates to the initial experience during SCENT trial.

Common late complications of longitudinal forefoot amputations in neuropathic foot treatment

2021 ◽  
Vol 30 (6) ◽  
pp. 498-503
Author(s):  
Rodrigo Sousa Macedo ◽  
Lucas Sousa Macedo ◽  
Marcos Hideyo Sakaki ◽  
Rafael Barban Sposeto ◽  
Rafael Trevisan Ortiz ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Reoperation Rate ◽  
Late Complications ◽  
Inclusion Criteria ◽  
Patients With Diabetes ◽  
Partial Amputation ◽  
Neuropathic Foot ◽  
Foot Clinic ◽  
Ray Amputation

Objective: To describe and quantify the complications arising in consecutive neuropathic patients undergoing partial longitudinal amputations of the foot. Method: A retrospective study was conducted with data collected from the medical records of patients monitored at the Insensitive Foot Clinic of the Foot and Ankle Group of our institution who underwent partial amputation of foot rays from 2000 to 2016. Results: A total of 28 patients met the inclusion criteria, with a total of 31 amputated/partially amputated feet. Of these, 18 (58.1%) feet were amputated/partially amputated due to diabetes, seven (22.6%) due to leprosy, two (6.5%) due to alcoholic neuropathy, two (6.5%) secondary to traumatic peripheral nerve injury, and two (6.5%) due to other causes. Fifth ray amputation was the most frequent type (n=12). The cause of amputation was the presence of an infected ulcer in 93.6% of the samples. At a mean follow-up time of 60 months, 13 (41.9%) feet required new amputations—five (38.5%) transtibial, five (38.5%) transmetatarsal, two (15.4%) of the toes, and one (7.7%) at Chopart's joint. Patients with diabetes had a 50.0% reamputation rate. Patients who initially underwent amputation of the fifth ray had a 58.3% reamputation rate. Conclusion: Partial longitudinal amputation of the foot in neuropathic patients exhibited a high reoperation rate, especially in patients with diabetes or in patients with initial amputation of the peripheral rays. Declaration of interest: The authors have no conflicts of interest.

Ethics and equity in rare disease research and healthcare

2021 ◽  
Author(s):  
Maria Koromina ◽  
Vasileios Fanaras ◽  
Gareth Baynam ◽  
Christina Mitropoulou ◽  
George P Patrinos
Keyword(s):  
Rare Diseases ◽  
Ethical Issues ◽  
Genetic Diseases ◽  
Ethical Framework ◽  
Middle Income ◽  
Next Generation Sequencing Technology ◽  
Ethical Frameworks ◽  
Rare Genetic Diseases ◽  
Conducting Research ◽  
Key Aspects

Rapid advances in next-generation sequencing technology, particularly whole exome sequencing and whole genome sequencing, have greatly affected our understanding of genetic variation underlying rare genetic diseases. Herein, we describe ethical principles of guiding consent and sharing of genomics research data. We also discuss ethical dilemmas in rare diseases research and patient recruitment policies and address bioethical and societal aspects influencing the ethical framework for genetic testing. Moreover, we focus on addressing ethical issues surrounding research in low- and middle-income countries. Overall, this perspective aims to address key aspects and issues for building proper ethical frameworks, when conducting research involving genomics data with a particular emphasis on rare diseases and genetics testing.

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