Boesch S and Indelicato E (2019); Front. Neurosci. 13:386. doi: 10.3389/fnins.2019.00386
Despite several clinical trials in the past, no treatment is available for the treatment of FRDA. Current lines of research focus on gene therapy, frataxin replacement strategies and on regulation of key metabolic checkpoints such as NrF2. Due to potential crosstalk with all these mechanisms, interventions on the EPO pathway still represent a valuable research field. The recent development of small EPO mimetics which maintain cytoprotective properties without erythropoietic action may open a new era in EPO research for the treatment of FRDA.
Thursday, April 25, 2019
Tuesday, April 23, 2019
A Clinical Study to Evaluate the Effect of MIN-102 on the Progression of Friedreich's Ataxia in Male and Female Patients (FRAMES)
ClinicalTrials.gov Identifier: NCT03917225.
Double-Blind, Placebo-controlled Study on the Effects of MIN-102 on Biochemical, Imaging, Neurophisyiological, and Clinical Markers in Patients With Friedreich's Ataxia.
Sponsor: Minoryx Therapeutics, S.L.
Locations
Belgium
Hôpital Erasme-ULB Not yet recruiting
Brussels, Belgium, B-1070
Contact: Prof. Massimo Pandolfo
France
ICM, Groupe Hospitalier Pitié Salpêtrière Not yet recruiting
Paris, France, 75646
Contact: Prof. Alexandra Durr
Germany
Universitätsklinikum RWTH Not yet recruiting
Aachen, Germany, 52074
Contact: Prof. Jörg B Schulz
Spain
Hospital Sant Joan de Déu Not yet recruiting
Barcelona, Spain
Contact: Dr. Alejandra Darling
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Dr. Francisco Javier Rodríguez de Rivera
Double-Blind, Placebo-controlled Study on the Effects of MIN-102 on Biochemical, Imaging, Neurophisyiological, and Clinical Markers in Patients With Friedreich's Ataxia.
Sponsor: Minoryx Therapeutics, S.L.
Locations
Belgium
Hôpital Erasme-ULB Not yet recruiting
Brussels, Belgium, B-1070
Contact: Prof. Massimo Pandolfo
France
ICM, Groupe Hospitalier Pitié Salpêtrière Not yet recruiting
Paris, France, 75646
Contact: Prof. Alexandra Durr
Germany
Universitätsklinikum RWTH Not yet recruiting
Aachen, Germany, 52074
Contact: Prof. Jörg B Schulz
Spain
Hospital Sant Joan de Déu Not yet recruiting
Barcelona, Spain
Contact: Dr. Alejandra Darling
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Dr. Francisco Javier Rodríguez de Rivera
Association between restless legs syndrome and other movement disorders
Hortensia Alonso-Navarro, Elena García-Martín, José A.G. Agúndez, View ORCID ProfileFélix Javier Jiménez-Jiménez; Neurology. 2019 Apr 19. pii: 10.1212/WNL.0000000000007500. doi: 10.1212/WNL.0000000000007500.
Review of PubMed from 1966 to September 2018 and identification of references of interest for the topic. A meta-analysis of eligible studies on the frequency of RLS in patients with PD and controls using Meta-DiSc1.1.1 software and using the PRISMA guidelines was performed.
Several studies have also suggested that RLS could be an early clinical feature of PD. RLS symptoms are frequent in multiple system atrophy, essential tremor, Tourette syndrome, Friedreich ataxia, and spinocerebellar ataxia type 3 as well.
Review of PubMed from 1966 to September 2018 and identification of references of interest for the topic. A meta-analysis of eligible studies on the frequency of RLS in patients with PD and controls using Meta-DiSc1.1.1 software and using the PRISMA guidelines was performed.
Several studies have also suggested that RLS could be an early clinical feature of PD. RLS symptoms are frequent in multiple system atrophy, essential tremor, Tourette syndrome, Friedreich ataxia, and spinocerebellar ataxia type 3 as well.
Friday, April 12, 2019
Mechanism of frataxin “bypass” in human iron-sulfur cluster biosynthesis with implications for Friedreich’s ataxia
Deepika Das, Shachin Patra, Jennifer Bridwell-Rabb, and David P. Barondeau; J. Biol. Chem. jbc.RA119.007716. doi:10.1074/jbc.RA119.007716
These results reveal an unexpected mechanism that replaces FXN-based stimulation of the Fe-S cluster biosynthetic pathway and suggest new strategies to overcome the loss of cellular FXN that may be relevant to the development of therapeutics for Friedreich’s ataxia.
These results reveal an unexpected mechanism that replaces FXN-based stimulation of the Fe-S cluster biosynthetic pathway and suggest new strategies to overcome the loss of cellular FXN that may be relevant to the development of therapeutics for Friedreich’s ataxia.
Tuesday, April 2, 2019
L’ataxie de Friedreich : la particularité subsaharienne
Ale Thiam, Amadou Koura Ndao, Mansour Ndiaye, Fatou Diouf Sene, Amadou Gallo Diop, Ibrahima Pierre Ndiaye, Astou Thiam, Revue Neurologique, Volume 175, Supplement 1, 2019, Page S127, doi:10.1016/j.neurol.2019.01.333.
Notre prévalence de cas d’AF est faible. La symptomatologie était moindre au Sénégal comparativement à la population caucasienne. Cependant, la conscientisation de la population autour des facteurs socio-ethniques est nécessaire.
Notre prévalence de cas d’AF est faible. La symptomatologie était moindre au Sénégal comparativement à la population caucasienne. Cependant, la conscientisation de la population autour des facteurs socio-ethniques est nécessaire.
Saturday, March 30, 2019
StrideBio and Takeda Enter Collaboration and License Agreement to Advance Novel Gene Therapies for Neurological Diseases
DURHAM, N.C., March 28, 2019 /PRNewswire/ — StrideBio, Inc, a leading developer of novel adeno-associated viral (AAV) based gene therapies, today announced the signing of a collaboration and license agreement with Takeda Pharmaceutical Company Limited (Takeda) to develop in vivo AAV based therapies for Friedreich’s Ataxia (FA) and two additional undisclosed targets. These programs aim to utilize novel AAV capsids developed by StrideBio to improve potency, evade neutralizing antibodies and enhance specific tropism to tissues including the central nervous system.
Thursday, March 28, 2019
New Insights into the Hepcidin-Ferroportin Axis and Iron Homeostasis in iPSC-Derived Cardiomyocytes from Friedreich’s Ataxia Patient
Alessandra Bolotta, Provvidenza Maria Abruzzo, Vito Antonio Baldassarro, Alessandro Ghezzo, Katia Scotlandi, Marina Marini and Cinzia Zucchini, Oxidative Medicine and Cellular Longevity, vol. 2019, Article ID 7623023, 11 pages, 2019. doi:10.1155/2019/7623023.
Iron homeostasis in the cardiac tissue as well as the involvement of the hepcidin-ferroportin (HAMP-FPN) axis in this process and in cardiac functionality are not fully understood. Imbalance of iron homeostasis occurs in several cardiac diseases, including iron-overload cardiomyopathies such as Friedreich’s ataxia (FRDA, OMIM no. 229300), a hereditary neurodegenerative disorder. Exploiting the induced pluripotent stem cells (iPSCs) technology and the iPSC capacity to differentiate into specific cell types, we derived cardiomyocytes of a FRDA patient and of a healthy control subject in order to study the cardiac iron homeostasis and the HAMP-FPN axis. Both CTR and FRDA iPSCs-derived cardiomyocytes express cardiac differentiation markers; in addition, FRDA cardiomyocytes maintain the FRDA-like phenotype. We found that FRDA cardiomyocytes show an increase in the protein expression of HAMP and FPN. Moreover, immunofluorescence analysis revealed for the first time an unexpected nuclear localization of FPN in both CTR and FRDA cardiomyocytes. However, the amount of the nuclear FPN was less in FRDA cardiomyocytes than in controls. These and other data suggest that iron handling and the HAMP-FPN axis regulation in FRDA cardiac cells are hampered and that FPN may have new, still not fully understood, functions. These findings underline the complexity of the cardiac iron homeostasis.
Iron homeostasis in the cardiac tissue as well as the involvement of the hepcidin-ferroportin (HAMP-FPN) axis in this process and in cardiac functionality are not fully understood. Imbalance of iron homeostasis occurs in several cardiac diseases, including iron-overload cardiomyopathies such as Friedreich’s ataxia (FRDA, OMIM no. 229300), a hereditary neurodegenerative disorder. Exploiting the induced pluripotent stem cells (iPSCs) technology and the iPSC capacity to differentiate into specific cell types, we derived cardiomyocytes of a FRDA patient and of a healthy control subject in order to study the cardiac iron homeostasis and the HAMP-FPN axis. Both CTR and FRDA iPSCs-derived cardiomyocytes express cardiac differentiation markers; in addition, FRDA cardiomyocytes maintain the FRDA-like phenotype. We found that FRDA cardiomyocytes show an increase in the protein expression of HAMP and FPN. Moreover, immunofluorescence analysis revealed for the first time an unexpected nuclear localization of FPN in both CTR and FRDA cardiomyocytes. However, the amount of the nuclear FPN was less in FRDA cardiomyocytes than in controls. These and other data suggest that iron handling and the HAMP-FPN axis regulation in FRDA cardiac cells are hampered and that FPN may have new, still not fully understood, functions. These findings underline the complexity of the cardiac iron homeostasis.
Tuesday, March 26, 2019
Open Trail of γIFN for Friedreich Ataxia
ClinicalTrials.gov Identifier: NCT03888664. IRCCS Eugenio Medea
The investigator proposes an open label pilot study to investigate the safety and efficacy of gamma interferon (γIFN) in patients with Friedreich's Ataxia (FRDA). yIFN, an approved drug for treatment of granulomatous disease, has been shown to promote Frataxin expression in FRDA models in vitro and in vivo as well as in pilot human studies.
Safety will monitored by clinical surveillance and biohumoral periodic assessment. Efficacy will be assessed by a combination of advanced neuroimaging techniques and established clinical indicators. The investigators intend to recruit over a 6 months period 12 subject with molecularly established FRDA. The protocol builds on a recently concluded observational study which established the pattern of clinical and neuroimaging abnormalities characterizing a cohort of patients with FA. The data already acquired through such study will constitute the T -12 point, and together with T0 assessment, carried out at study entrance, will provide for each patient the exact appreciation of disease actual progression over a year time. Recruited patients will receive for 6 months yIFN at a final dose of 200 ug/three times a week. Patients will be evaluated clinically after 3 and 6 months (t3 and T6) of treatment and 6 months after treatment end (T+6) and by neuroimaging at T6 and T+6. The neuroimaging protocol, based on 3 Tesla scanner, consists in functional MRI, tractography and brain iron content measurement. The clinical protocol consists on specific ataxia scales administration. Regular monitoring with for eventual adverse events will be provided. Frataxin levels in the peripheral blood mononuclear cells will also be evaluated at T0, T3, T6, T+6. In addition cardiac ventricular thickness and contrast vision will be followed at T0, T6, T+6.
The investigator proposes an open label pilot study to investigate the safety and efficacy of gamma interferon (γIFN) in patients with Friedreich's Ataxia (FRDA). yIFN, an approved drug for treatment of granulomatous disease, has been shown to promote Frataxin expression in FRDA models in vitro and in vivo as well as in pilot human studies.
Safety will monitored by clinical surveillance and biohumoral periodic assessment. Efficacy will be assessed by a combination of advanced neuroimaging techniques and established clinical indicators. The investigators intend to recruit over a 6 months period 12 subject with molecularly established FRDA. The protocol builds on a recently concluded observational study which established the pattern of clinical and neuroimaging abnormalities characterizing a cohort of patients with FA. The data already acquired through such study will constitute the T -12 point, and together with T0 assessment, carried out at study entrance, will provide for each patient the exact appreciation of disease actual progression over a year time. Recruited patients will receive for 6 months yIFN at a final dose of 200 ug/three times a week. Patients will be evaluated clinically after 3 and 6 months (t3 and T6) of treatment and 6 months after treatment end (T+6) and by neuroimaging at T6 and T+6. The neuroimaging protocol, based on 3 Tesla scanner, consists in functional MRI, tractography and brain iron content measurement. The clinical protocol consists on specific ataxia scales administration. Regular monitoring with for eventual adverse events will be provided. Frataxin levels in the peripheral blood mononuclear cells will also be evaluated at T0, T3, T6, T+6. In addition cardiac ventricular thickness and contrast vision will be followed at T0, T6, T+6.
Monday, March 25, 2019
Therapeutic Prospects for Friedreich’s Ataxia
Siyuan Zhang, Marek Napierala, Jill S. Napierala; Trends in Pharmacological Sciences, Volume 40, Issue 4, 2019, Pages 229-233, doi:10.1016/j.tips.2019.02.001.
Friedreich’s ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure.
Friedreich’s ataxia (FRDA) is a progressive disease affecting multiple organs that is caused by systemic insufficiency of the mitochondrial protein frataxin. Current therapeutic strategies aim to elevate frataxin levels and/or alleviate the consequences of frataxin deficiency. Recent significant advances in the FRDA therapeutic pipeline are bringing patients closer to a cure.
Thursday, March 21, 2019
Ion Mobility-Mass Spectrometry Reveals Details of Formation and Structure for GAA·TCC DNA and RNA Triplexes
Jiawei Li, Alexander Begbie, Belinda J. Boehm, Alexander Button, Charles Whidborne, Yannii Pouferis, David M. Huang, Tara L. Pukala; J. Am. Soc. Mass Spectrom. (2019) 30: 103. doi:10.1007/s13361-018-2077-9
DNA and RNA triplexes are thought to play key roles in a range of cellular processes such as gene regulation and epigenetic remodeling and have been implicated in human disease such as Friedreich’s ataxia. In this work, ion mobility-mass spectrometry (IM-MS) is used with supporting UV-visible spectroscopy to investigate DNA triplex assembly, considering stability and specificity, for GAA·TTC oligonucleotide sequences of relevance to Friedreich’s ataxia.
DNA and RNA triplexes are thought to play key roles in a range of cellular processes such as gene regulation and epigenetic remodeling and have been implicated in human disease such as Friedreich’s ataxia. In this work, ion mobility-mass spectrometry (IM-MS) is used with supporting UV-visible spectroscopy to investigate DNA triplex assembly, considering stability and specificity, for GAA·TTC oligonucleotide sequences of relevance to Friedreich’s ataxia.
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