Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
6.1
4.3
Journals
Pharmaceuticals
Special Issues
Drug Design and Development for Rare Hematologic Diseases
share announcement

Drug Design and Development for Rare Hematologic Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (25 March 2022) | Viewed by 39379

Special Issue Editors

Dr. Bruno Fattizzo

E-Mail Website
Guest Editor
Department of Oncology and Hemato-oncology, University of Milan, 20122 Milan, Italy
Interests: rare anemias; autoimmune hemolytic anemia; autoimmune thrombocytopenia; autoimmune neutropenia; aplastic anemia; paroxysmal nocturnal hemoglobinuria; congenital hemolytic anemias
Dr. Irene Motta

E-Mail Website
Guest Editor
Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy
Interests: rare anemias
Dr. Marco Capecchi

E-Mail Website
Guest Editor
1. Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, 20122 Milan, Italy
2. Department of Biomedical Sciences for Health, University of Milan, 20112 Milan, Italy
Interests: thrombosis; hemostasis; venous thrombosis; platelet disorders

Special Issue Information

Dear Colleagues,

The last decade has seen an exponential increase in therapeutic options for rare hematologic diseases. The latter encompass benign conditions, including congenital anemias, autoimmune cytopenias, bone marrow failure syndromes (i.e., aplastic anemia and paroxysmal nocturnal hemoglobinuria), and rare hemostatic disorders, as well as neoplastic ones (i.e., low risk myelodysplastic syndromes and systemic mastocytosis). Moreover, rare metabolic disorders such as Gaucher disease may involve bone marrow and result in cytopenic phenotype and have gained clinical attention since novel substitutive therapies have been developed. On the whole, these disorders often represent a diagnostic challenge given their rarity, but also due to their heterogeneous clinical phenotype. Once diagnosed, many of them are treated with supportive therapies only (i.e., blood and plasma transfusions, plasmapheresis, etc.) for many years, representing a true unmet need. Novel treatment strategies include oral small molecules, intravenous or subcutaneous monoclonal antibodies, small interfering RNAs, gene therapy, and many others. All of these therapies are at different phases of development (either preclinical or clinical) and will likely be positioned at different disease stages or in specific settings. Along efficacy, which may vary according to disease phenotype, new toxicities are emerging, and novel specific monitoring and preventive strategies will be developed. Finally, each novel treatment poses a challenge to the treating physician who will have to choose the best therapy for the best patient. In this Special Issue of Pharmaceuticals, we aim to collect all types of articles (original manuscripts, reviews, and case reports) dealing with novel drugs under development for rare hematologic conditions. Manuscript focusing on any aspects of efficacy, safety, and management of novel targeted therapies, or on predictors of response, will be welcomed.

Dr. Bruno Fattizzo
Dr. Irene Motta
Dr. Marco Capecchi
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • rare anemias
  • autoimmune hemolytic anemia
  • autoimmune thrombocytopenia
  • autoimmune neutropenia
  • aplastic anemia
  • paroxysmal nocturnal hemoglobinuria
  • congenital hemolytic anemias
  • myelodysplastic syndromes
  • systemic mastocytosis
  • thalassemias
  • sickle cell anemia
  • Gaucher disease
  • Fabry disease
  • thrombotic microangiopathies
  • hemophilia

Benefits of Publishing in a Special Issue

  • Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
  • Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
  • Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
  • External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
  • e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (9 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Editorial

Jump to: Review, Other

2 pages, 195 KiB  
Editorial
Drug Design and Development for Rare Hematologic Diseases
by Bruno Fattizzo, Marco Capecchi and Irene Motta
Pharmaceuticals 2023, 16(10), 1469; https://doi.org/10.3390/ph16101469 - 16 Oct 2023
Viewed by 920
Abstract
The last decade has seen an exponential increase in therapeutic options for rare hematologic diseases [...] Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)

Review

Jump to: Editorial, Other

19 pages, 1086 KiB  
Review
Interpreting Iron Homeostasis in Congenital and Acquired Disorders
by Natalia Scaramellini, Dania Fischer, Anand R. Agarvas, Irene Motta, Martina U. Muckenthaler and Christina Mertens
Pharmaceuticals 2023, 16(3), 329; https://doi.org/10.3390/ph16030329 - 21 Feb 2023
Cited by 5 | Viewed by 3747
Abstract
Mammalian cells require iron to satisfy their metabolic needs and to accomplish specialized functions, such as hematopoiesis, mitochondrial biogenesis, energy metabolism, or oxygen transport. Iron homeostasis is balanced by the interplay of proteins responsible for iron import, storage, and export. A misbalance of [...] Read more.
Mammalian cells require iron to satisfy their metabolic needs and to accomplish specialized functions, such as hematopoiesis, mitochondrial biogenesis, energy metabolism, or oxygen transport. Iron homeostasis is balanced by the interplay of proteins responsible for iron import, storage, and export. A misbalance of iron homeostasis may cause either iron deficiencies or iron overload diseases. The clinical work-up of iron dysregulation is highly important, as severe symptoms and pathologies may arise. Treating iron overload or iron deficiency is important to avoid cellular damage and severe symptoms and improve patient outcomes. The impressive progress made in the past years in understanding mechanisms that maintain iron homeostasis has already changed clinical practice for treating iron-related diseases and is expected to improve patient management even further in the future. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

18 pages, 782 KiB  
Review
Updates on Novel Non-Replacement Drugs for Hemophilia
by Roberta Gualtierotti, Samantha Pasca, Alessandro Ciavarella, Sara Arcudi, Andrea Giachi, Isabella Garagiola, Chiara Suffritti, Simona Maria Siboni and Flora Peyvandi
Pharmaceuticals 2022, 15(10), 1183; https://doi.org/10.3390/ph15101183 - 23 Sep 2022
Cited by 20 | Viewed by 5542
Abstract
Over the last decade, the world of hemophilia has experienced an unprecedented therapeutic advance, thanks to the progress in bioengineering technologies, leading to the introduction of drugs with novel mechanisms of action based on restoring thrombin generation or coagulation factor VIII mimicking. Apart [...] Read more.
Over the last decade, the world of hemophilia has experienced an unprecedented therapeutic advance, thanks to the progress in bioengineering technologies, leading to the introduction of drugs with novel mechanisms of action based on restoring thrombin generation or coagulation factor VIII mimicking. Apart from the bispecific monoclonal antibody emicizumab, already approved for patients with severe hemophilia A with and without inhibitors, novel non-replacement drugs designed to reduce the treatment burden of patients with hemophilia A or B with or without inhibitors are undergoing evaluation in clinical trials. Thanks to their innovative mechanism of action and subcutaneous administration, these drugs promise to provide effective bleeding protection together with improved adherence and improve health-related quality of life for patients with hemophilia. On the other hand, rare thromboembolic events have been reported with some of these drugs and warrant continuous post-marketing surveillance and investigation of predisposing factors, although the overall safety profile of most of these drugs is good. Finally, new challenges need to be faced in the clinical and laboratory monitoring of the hemostatic status in patients treated with these innovative therapies. In this review, we provide an update on the available data on novel non-replacement drugs currently undergoing evaluation in clinical trials for patients with hemophilia. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

14 pages, 690 KiB  
Review
Complement System as a New Target for Hematopoietic Stem Cell Transplantation-Related Thrombotic Microangiopathy
by Gianluigi Ardissino, Valentina Capone, Silvana Tedeschi, Luigi Porcaro and Massimo Cugno
Pharmaceuticals 2022, 15(7), 845; https://doi.org/10.3390/ph15070845 - 9 Jul 2022
Cited by 12 | Viewed by 4394
Abstract
Thrombotic microangiopathy (TMA) is a complication that may occur after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and is conventionally called transplant-associated thrombotic microangiopathy (TA-TMA). Despite the many efforts made to understand the mechanisms of TA-TMA, its pathogenesis is largely unknown, its [...] Read more.
Thrombotic microangiopathy (TMA) is a complication that may occur after autologous or allogeneic hematopoietic stem cell transplantation (HSCT) and is conventionally called transplant-associated thrombotic microangiopathy (TA-TMA). Despite the many efforts made to understand the mechanisms of TA-TMA, its pathogenesis is largely unknown, its diagnosis is challenging and the case-fatality rate remains high. The hallmarks of TA-TMA, as for any TMA, are platelet consumption, hemolysis, and organ dysfunction, particularly the kidney, leading also to hypertension. However, coexisting complications, such as infections and/or immune-mediated injury and/or drug toxicity, together with the heterogeneity of diagnostic criteria, render the diagnosis difficult. During the last 10 years, evidence has been provided on the involvement of the complement system in the pathophysiology of TA-TMA, supported by functional, genetic, and therapeutic data. Complement dysregulation is believed to collaborate with other proinflammatory and procoagulant factors to cause endothelial injury and consequent microvascular thrombosis and tissue damage. However, data on complement activation in TA-TMA are not sufficient to support a systematic use of complement inhibition therapy in all patients. Thus, it seems reasonable to propose complement inhibition therapy only to those patients exhibiting a clear complement activation according to the available biomarkers. Several agents are now available to inhibit complement activity: two drugs have been successfully used in TA-TMA, particularly in pediatric cases (eculizumab and narsoplimab) and others are at different stages of development (ravulizumab, coversin, pegcetacoplan, crovalimab, avacopan, iptacopan, danicopan, BCX9930, and AMY-101). Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

24 pages, 939 KiB  
Review
Novel Therapies to Address Unmet Needs in ITP
by María Eva Mingot-Castellano, José María Bastida, Gonzalo Caballero-Navarro, Laura Entrena Ureña, Tomás José González-López, José Ramón González-Porras, Nora Butta, Mariana Canaro, Reyes Jiménez-Bárcenas, María del Carmen Gómez del Castillo Solano, Blanca Sánchez-González, Cristina Pascual-Izquierdo and on behalf of the GEPTI
Pharmaceuticals 2022, 15(7), 779; https://doi.org/10.3390/ph15070779 - 23 Jun 2022
Cited by 14 | Viewed by 4332
Abstract
Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical [...] Read more.
Primary immune thrombocytopenia (ITP) is an autoimmune disorder that causes low platelet counts and subsequent bleeding risk. Although current corticosteroid-based ITP therapies are able to improve platelet counts, up to 70% of subjects with an ITP diagnosis do not achieve a sustained clinical response in the absence of treatment, thus requiring a second-line therapy option as well as additional care to prevent bleeding. Less than 40% of patients treated with thrombopoietin analogs, 60% of those treated with splenectomy, and 20% or fewer of those treated with rituximab or fostamatinib reach sustained remission in the absence of treatment. Therefore, optimizing therapeutic options for ITP management is mandatory. The pathophysiology of ITP is complex and involves several mechanisms that are apparently unrelated. These include the clearance of autoantibody-coated platelets by splenic macrophages or by the complement system, hepatic desialylated platelet destruction, and the inhibition of platelet production from megakaryocytes. The number of pathways involved may challenge treatment, but, at the same time, offer the possibility of unveiling a variety of new targets as the knowledge of the involved mechanisms progresses. The aim of this work, after revising the limitations of the current treatments, is to perform a thorough review of the mechanisms of action, pharmacokinetics/pharmacodynamics, efficacy, safety, and development stage of the novel ITP therapies under investigation. Hopefully, several of the options included herein may allow us to personalize ITP management according to the needs of each patient in the near future. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

17 pages, 724 KiB  
Review
Pharmacological Induction of Fetal Hemoglobin in β-Thalassemia and Sickle Cell Disease: An Updated Perspective
by Rayan Bou-Fakhredin, Lucia De Franceschi, Irene Motta, Maria Domenica Cappellini and Ali T. Taher
Pharmaceuticals 2022, 15(6), 753; https://doi.org/10.3390/ph15060753 - 16 Jun 2022
Cited by 21 | Viewed by 5440
Abstract
A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in [...] Read more.
A significant amount of attention has recently been devoted to the mechanisms involved in hemoglobin (Hb) switching, as it has previously been established that the induction of fetal hemoglobin (HbF) production in significant amounts can reduce the severity of the clinical course in diseases such as β-thalassemia and sickle cell disease (SCD). While the induction of HbF using lentiviral and genome-editing strategies has been made possible, they present limitations. Meanwhile, progress in the use of pharmacologic agents for HbF induction and the identification of novel HbF-inducing strategies has been made possible as a result of a better understanding of γ-globin regulation. In this review, we will provide an update on all current pharmacological inducer agents of HbF in β-thalassemia and SCD in addition to the ongoing research into other novel, and potentially therapeutic, HbF-inducing agents. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

17 pages, 820 KiB  
Review
Target Therapies for Systemic Mastocytosis: An Update
by Mariarita Sciumè, Claudio De Magistris, Nicole Galli, Eleonora Ferretti, Giulia Milesi, Pasquale De Roberto, Sonia Fabris and Federica Irene Grifoni
Pharmaceuticals 2022, 15(6), 738; https://doi.org/10.3390/ph15060738 - 11 Jun 2022
Cited by 5 | Viewed by 3578
Abstract
Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra-cutaneous organs. It could be divided into indolent SM, smoldering SM, SM with an associated hematologic (non-MC lineage) neoplasm, aggressive SM, and mast cell leukemia. SM is generally associated [...] Read more.
Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MCs) in extra-cutaneous organs. It could be divided into indolent SM, smoldering SM, SM with an associated hematologic (non-MC lineage) neoplasm, aggressive SM, and mast cell leukemia. SM is generally associated with the presence of a gain-of-function somatic mutation in KIT at codon 816. Clinical features could be related to MC mediator release or to uncontrolled infiltration of MCs in different organs. Whereas indolent forms have a near-normal life expectancy, advanced diseases have a poor prognosis with short survival times. Indolent forms should be considered for symptom-directed therapy, while cytoreductive therapy represents the first-line treatment for advanced diseases. Since the emergence of tyrosine kinase inhibitors (TKIs), KIT inhibition has been an attractive approach. Initial reports showed that only the rare KITD816V negative cases were responsive to first-line TKI imatinib. The development of new TKIs with activity against the KITD816V mutation, such as midostaurin or avapritinib, has changed the management of this disease. This review aims to focus on the available clinical data of therapies for SM and provide insights into possible future therapeutic targets. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

24 pages, 1137 KiB  
Review
Targeting the Hematopoietic Stem Cell Niche in β-Thalassemia and Sickle Cell Disease
by Annamaria Aprile, Silvia Sighinolfi, Laura Raggi and Giuliana Ferrari
Pharmaceuticals 2022, 15(5), 592; https://doi.org/10.3390/ph15050592 - 11 May 2022
Cited by 6 | Viewed by 6699
Abstract
In the last decade, research on pathophysiology and therapeutic solutions for β-thalassemia (BThal) and sickle cell disease (SCD) has been mostly focused on the primary erythroid defect, thus neglecting the study of hematopoietic stem cells (HSCs) and bone marrow (BM) microenvironment. The quality [...] Read more.
In the last decade, research on pathophysiology and therapeutic solutions for β-thalassemia (BThal) and sickle cell disease (SCD) has been mostly focused on the primary erythroid defect, thus neglecting the study of hematopoietic stem cells (HSCs) and bone marrow (BM) microenvironment. The quality and engraftment of HSCs depend on the BM microenvironment, influencing the outcome of HSC transplantation (HSCT) both in allogeneic and in autologous gene therapy settings. In BThal and SCD, the consequences of severe anemia alter erythropoiesis and cause chronic stress in different organs, including the BM. Here, we discuss the recent findings that highlighted multiple alterations of the BM niche in BThal and SCD. We point out the importance of improving our understanding of HSC biology, the status of the BM niche, and their functional crosstalk in these disorders towards the novel concept of combined therapies by not only targeting the genetic defect, but also key players of the HSC–niche interaction in order to improve the clinical outcomes of transplantation. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Figure 1

Other

Jump to: Editorial, Review

13 pages, 2337 KiB  
Case Report
Efficacy and Immunomodulating Properties of Eltrombopag in Aplastic Anemia following Autologous Stem Cell Transplant: Case Report and Review of the Literature
by Marta Bortolotti, Loredana Pettine, Anna Zaninoni, Giorgio Alberto Croci, Wilma Barcellini and Bruno Fattizzo
Pharmaceuticals 2022, 15(4), 419; https://doi.org/10.3390/ph15040419 - 30 Mar 2022
Cited by 5 | Viewed by 3378
Abstract
Thrombopoietin receptor agonists (TPO-RA) are currently indicated for the treatment of chronic immune thrombocytopenia and relapsed refractory aplastic anemia. However, the off-label use of these drugs is more and more frequent, including in the setting of aplasia secondary to chemotherapy and hemopoietic stem [...] Read more.
Thrombopoietin receptor agonists (TPO-RA) are currently indicated for the treatment of chronic immune thrombocytopenia and relapsed refractory aplastic anemia. However, the off-label use of these drugs is more and more frequent, including in the setting of aplasia secondary to chemotherapy and hemopoietic stem cell transplant (SCT). Growing evidence suggests that mechanisms of action of TPO-RA go beyond the TPO-receptor stimulation and point at the immunomodulating properties of these drugs. Here, we present a case of prolonged bone marrow aplasia secondary to autologous SCT treated with eltrombopag. We describe the clinical efficacy and the immunomodulating effect of this drug on inflammatory cytokine profile and bone marrow histology. Furthermore, we provide a review of the most recent literature highlighting the efficacy and safety of TPO-RA after SCT and chemotherapy for hematologic conditions. Full article
(This article belongs to the Special Issue Drug Design and Development for Rare Hematologic Diseases)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-9
Back to TopTop