Daria Korchagina, Aurelie Millier, Anne-Lise Vataire, Samuel Aballea, Bruno Falissard and Mondher Toumi; Orphanet Journal of Rare Diseases 201712:75 DOI: 10.1186/s13023-016-0561-5 Published: 21 April 2017
The introduction of the orphan drug legislation led to the increase in the number of available orphan drugs, but the access to them is often limited due to the high price. Social preferences regarding funding orphan drugs as well as the criteria taken into consideration while setting the price remain unclear.
Decisions on orphan drug prices remain non transparent in most of cases. A robust comprehensive framework is needed to assess orphan drugs value. Several methodologies have been proposed mostly based on the multi-criteria decision analysis.
Tuesday, April 25, 2017
Monday, April 24, 2017
CA Cycle in the Dentate in Friedreich's Ataxia
ClinicalTrials.gov Identifier: NCT03122925 First received: April 18, 2017
OBJECTIVE: To measure the tricarboxylic acid (TCA) cycle rate in the dentate nucleus in a group of control subjects and subjects with Friedreich's Ataxia (FRDA).
HYPOTHESIS: The TCA cycle rate will be lower in FRDA subjects than in controls APPROACH: We will infuse carbon-13 (13C) labeled glucose and measure the rate of 13C label incorporation from glucose to glutamate in the brain using in vivo magnetic resonance spectroscopy.
Detailed Description:
We will measure the TCA cycle rate in the dentate nucleus in a group of FRDA patients and in a group of age-matched healthy controls using 13C MRS in vivo together with systemic i.v. infusion of 13C-labeled glucose.
We aim to obtain adequate data in 16 subjects grouped as follows:
n=4 pilot subjects (healthy subjects) for testing and optimization of the experimental setup.
n=6 healthy controls
n=6 FRDA patients
Locations
United States, Minnesota
CMRR
Minneapolis, Minnesota, United States, 55455
Contact: Diane Hutter, RN 612-625-2350 hutte019@umn.edu
Principal Investigator: Pierre-Gilles Henry, PhD
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
OBJECTIVE: To measure the tricarboxylic acid (TCA) cycle rate in the dentate nucleus in a group of control subjects and subjects with Friedreich's Ataxia (FRDA).
HYPOTHESIS: The TCA cycle rate will be lower in FRDA subjects than in controls APPROACH: We will infuse carbon-13 (13C) labeled glucose and measure the rate of 13C label incorporation from glucose to glutamate in the brain using in vivo magnetic resonance spectroscopy.
Detailed Description:
We will measure the TCA cycle rate in the dentate nucleus in a group of FRDA patients and in a group of age-matched healthy controls using 13C MRS in vivo together with systemic i.v. infusion of 13C-labeled glucose.
We aim to obtain adequate data in 16 subjects grouped as follows:
n=4 pilot subjects (healthy subjects) for testing and optimization of the experimental setup.
n=6 healthy controls
n=6 FRDA patients
Locations
United States, Minnesota
CMRR
Minneapolis, Minnesota, United States, 55455
Contact: Diane Hutter, RN 612-625-2350 hutte019@umn.edu
Principal Investigator: Pierre-Gilles Henry, PhD
Sponsors and Collaborators
University of Minnesota - Clinical and Translational Science Institute
Friday, April 21, 2017
Orphan Drugs: Getting Arms around Rare Diseases
Duygu Koyuncu Irmak; J Comm Pub Health Nurs 2017, 3:2 DOI: 10.4172/2471-9846.1000167
Finding ways to bring new therapies for rare diseases to patients in a timely manner, effectively and affordably is an important public health challenge. The key concern for decision makers in the health authorities for all medicinal products including Orphan Drugs is that the treatment demonstrates efficacy through “substantial evidence” from adequate, well-planned, well-controlled clinical trials.
A successful clinical development programs in rare diseases starts with a tailored approach to ensure the right methodology is employed for the target rare disease therapy. The research methodology needs to be evaluated specifically for each rare disease and the target therapy in the light of all available scientific knowledge by all experts acting in all stakeholders.
Finding ways to bring new therapies for rare diseases to patients in a timely manner, effectively and affordably is an important public health challenge. The key concern for decision makers in the health authorities for all medicinal products including Orphan Drugs is that the treatment demonstrates efficacy through “substantial evidence” from adequate, well-planned, well-controlled clinical trials.
A successful clinical development programs in rare diseases starts with a tailored approach to ensure the right methodology is employed for the target rare disease therapy. The research methodology needs to be evaluated specifically for each rare disease and the target therapy in the light of all available scientific knowledge by all experts acting in all stakeholders.
Thursday, April 20, 2017
Rehabilitative Trial With Cerebello-Spinal tDCS in Neurodegenerative Ataxia (CStDCSAtaxia)
ClinicalTrials.gov Identifier: NCT03120013 First received: April 14, 2017
Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term.
Condition:
Ataxia, Cerebellar, Cerebellar Ataxia, Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia 3, Spinocerebellar Degenerations, Friedreich Ataxia, Ataxia With Oculomotor Apraxia, Multiple System Atrophy.
Intervention:
Device: Anodal cerebellar and cathodal spinal tDCS, Device: Sham cerebellar and sham spinal tDCS.
Locations:
Italy, AO Spedali Civili, Brescia, BS, Italy, 25100
Contact: Barbara Borroni
Neurodegenerative cerebellar ataxias represent a group of disabling disorders for which we currently lack effective therapies. Cerebellar transcranial direct current stimulation (tDCS) is a non-invasive technique, which has been demonstrated to modulate cerebellar excitability and improve symptoms in patients with cerebellar ataxias. In this randomized, double-blind, sham-controlled study, the investigators will evaluate whether a two-weeks' treatment with cerebellar anodal tDCS and spinal cathodal tDCS can improve symptoms in patients with neurodegenerative cerebellar ataxia and can modulate cerebello-motor connectivity, at short and long term.
Condition:
Ataxia, Cerebellar, Cerebellar Ataxia, Spinocerebellar Ataxias, Spinocerebellar Ataxia Type 1, Spinocerebellar Ataxia Type 2, Spinocerebellar Ataxia 3, Spinocerebellar Degenerations, Friedreich Ataxia, Ataxia With Oculomotor Apraxia, Multiple System Atrophy.
Intervention:
Device: Anodal cerebellar and cathodal spinal tDCS, Device: Sham cerebellar and sham spinal tDCS.
Locations:
Italy, AO Spedali Civili, Brescia, BS, Italy, 25100
Contact: Barbara Borroni
Saturday, April 15, 2017
Friedreich Ataxia: current status and future prospects
Bürk K; Cerebellum Ataxias. 2017 Apr 7;4:4. doi: 10.1186/s40673-017-0062-x. eCollection 2017.
This review gives an overview over clinical and genetic aspects of FA and discusses current concepts of frataxin biogenesis and function as well as new therapeutic strategies.
This review gives an overview over clinical and genetic aspects of FA and discusses current concepts of frataxin biogenesis and function as well as new therapeutic strategies.
Friday, April 14, 2017
Australian children living with rare diseases: experiences of diagnosis and perceived consequences of diagnostic delays
Yvonne Zurynski, Marie Deverell, Troy Dalkeith, Sandra Johnson, John Christodoulou, Helen Leonard, Elizabeth J Elliott and APSU Rare Diseases Impacts on Families Study group; Orphanet Journal of Rare Diseases201712:68 DOI: 10.1186/s13023-017-0622-4; Published: 11 April 2017
Parents of children living with rare chronic and complex diseases have called for better education, resourcing of health professionals to prevent avoidable diagnostic delays, and to facilitate access to early interventions and treatments. Access to psychological support and genetic counselling should be available to all parents receiving a life-changing diagnosis for their child.
The most common perceived reasons for delayed diagnosis reported by parents participating in our study was the lack of knowledge among health professionals.
Receiving a diagnosis of a rare chronic and complex disease for their child is a life-changing event for many families, and most require support at or near the time that diagnosis is made. Almost all parents in our study believed that psychological support should always be offered at the time of diagnosis.
Parents believe that health professionals’ knowledge about rare diseases needs to improve to enable more timely diagnosis, treatment, and provision of accurate information about the implications of the disease to families who are stressed, frustrated and anxious. The integration of genomic medicine into the health system, the establishment of multidisciplinary specialist clinics, and clear referral pathways may improve the timeliness and accuracy of diagnosis for children with rare diseases. The ultimate aim should be to improve patient and family experiences, and it is therefore imperative that patients are involved in development and evaluation of such programs.
Parents of children living with rare chronic and complex diseases have called for better education, resourcing of health professionals to prevent avoidable diagnostic delays, and to facilitate access to early interventions and treatments. Access to psychological support and genetic counselling should be available to all parents receiving a life-changing diagnosis for their child.
The most common perceived reasons for delayed diagnosis reported by parents participating in our study was the lack of knowledge among health professionals.
Receiving a diagnosis of a rare chronic and complex disease for their child is a life-changing event for many families, and most require support at or near the time that diagnosis is made. Almost all parents in our study believed that psychological support should always be offered at the time of diagnosis.
Parents believe that health professionals’ knowledge about rare diseases needs to improve to enable more timely diagnosis, treatment, and provision of accurate information about the implications of the disease to families who are stressed, frustrated and anxious. The integration of genomic medicine into the health system, the establishment of multidisciplinary specialist clinics, and clear referral pathways may improve the timeliness and accuracy of diagnosis for children with rare diseases. The ultimate aim should be to improve patient and family experiences, and it is therefore imperative that patients are involved in development and evaluation of such programs.
Thursday, April 13, 2017
No changes in heme synthesis in human Friedreich´s ataxia erythroid progenitor cells
Hannes Steinkellner, Himanshu Narayan Singh, Martina U. Muckenthaler, Hans Goldenberg, Rajeswari R. Moganty, Barbara Scheiber-Mojdehkar, Brigitte Sturm, Gene, Available online 12 April 2017, ISSN 0378-1119, doi:10.1016/j.gene.2017.04.014.
The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported.
FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis.
The mystery about the involvement of frataxin on iron metabolism raises the question why frataxin deficiency in primary FRDA cells did not lead to changes in biochemical parameters of heme synthesis. It seems that alternative pathways can circumvent the impact of frataxin deficiency on heme synthesis. We show for the first time in primary FRDA patient cells that reduced frataxin levels are still sufficient for heme synthesis and possibly other mechanisms can overcome reduced frataxin levels in this process. Our data strongly support the fact that so far no anemia in FRDA patients was reported.
FRDA patient cells showed no significant changes in iron levels, hemoglobin synthesis, protoporphyrin IX levels, and ferrochelatase activity. Microarray analysis presented 11 genes that were significantly changed in all patients compared to controls. The genes are especially involved in oxidative stress, iron homeostasis and angiogenesis.
Wednesday, April 12, 2017
Drugmakers accused of exploiting orphan drug incentives, fueling price problem
Brady Huggett, Nature Biotechnology 35, 301 (2017) doi:10.1038/nbt0417-301 Published online 11 April 2017
n January Kaiser Health News published a data-rich report focusing on the increase in approvals of orphan disease drugs, detailing how even high-volume products have reaped the tax breaks and market exclusivity that come with orphan drug status.
For each approval, drugmakers receive government incentives plus seven years exclusivity for that rare disease. Orphan status became a commercial opportunity.
Orphan drug rules “appear to be stretched beyond their original intent,” which may be helping to stoke drug prices for commonly used drugs.
n January Kaiser Health News published a data-rich report focusing on the increase in approvals of orphan disease drugs, detailing how even high-volume products have reaped the tax breaks and market exclusivity that come with orphan drug status.
For each approval, drugmakers receive government incentives plus seven years exclusivity for that rare disease. Orphan status became a commercial opportunity.
Orphan drug rules “appear to be stretched beyond their original intent,” which may be helping to stoke drug prices for commonly used drugs.
Tuesday, April 11, 2017
Biogen Accused Of Stifling Neurological Drug Competition
Law360, Los Angeles (April 4, 2017, 7:05 PM EDT) -- Biogen Inc. is facing an antitrust suit in California federal court filed Tuesday by Ixchel Pharma LLC alleging it attempted to hold a monopoly on drug treatments containing dimethyl fumarate, preventing Ixchel from creating a drug for a degenerative neurological disease.
The complaint claims Biogen specifically stopped a partnership between Ixchel and a competitor to develop a new treatment for Friedreich’s ataxia, a debilitating neuro-degenerative disorder. The condition doesn’t have an FDA-approved treatment, the complaint says, but Ixchel since 2012 has been working to develop one....
The complaint claims Biogen specifically stopped a partnership between Ixchel and a competitor to develop a new treatment for Friedreich’s ataxia, a debilitating neuro-degenerative disorder. The condition doesn’t have an FDA-approved treatment, the complaint says, but Ixchel since 2012 has been working to develop one....
Saturday, April 8, 2017
SNPs in microRNA target sites and their potential role in human disease
Adrianna Moszyńska, Magdalena Gebert, James F. Collawn, Rafał Bartoszewski; Open Biology, The Royal Society Publishing, Published 5 April 2017.DOI: 10.1098/rsob.170019
FXN | miR-124-3p: Reduced expression of the mitochondrial frataxin (FXN) protein has been postulated to play a role in Friedreich's ataxia (FRDA), an inherited neurodegenerative disease. Lower levels of frataxin are due to GAA repeat expansion in the FXN gene. Additionally, Bandiera et al. have suggested that miR-124-3p regulates FXN expression in vivo only in FRDA patients. They identified seven SNPs in the 3′-UTR of FXN in children and adults diagnosed with FRDA. One of them, rs11145043 (G>T), permits miR-124-3p binding only when the T allele is present. Although miR-124-3p is highly expressed in the nervous system, it is overexpressed in FRDA patients, suggesting its role in FRDA. However, its influence on FXN needs further clarification.
FXN | miR-124-3p: Reduced expression of the mitochondrial frataxin (FXN) protein has been postulated to play a role in Friedreich's ataxia (FRDA), an inherited neurodegenerative disease. Lower levels of frataxin are due to GAA repeat expansion in the FXN gene. Additionally, Bandiera et al. have suggested that miR-124-3p regulates FXN expression in vivo only in FRDA patients. They identified seven SNPs in the 3′-UTR of FXN in children and adults diagnosed with FRDA. One of them, rs11145043 (G>T), permits miR-124-3p binding only when the T allele is present. Although miR-124-3p is highly expressed in the nervous system, it is overexpressed in FRDA patients, suggesting its role in FRDA. However, its influence on FXN needs further clarification.
Subscribe to:
Posts (Atom)
