The Niche, Knoepfler lab stem cell blog. June 1, 2016.
The REGROW Act would drastically weaken FDA regulation of experimental stem cell therapies.
Patient Groups Opposing REGROW
Cystic Fibrosis Foundation
Friedreich’s Ataxia Research Alliance
Friends of Cancer Research
Global Genes
Michael J. Fox Foundation for Parkinson’s Research
Myotonic Dystrophy Foundation
National MS Society
National Organization for Rare Disorders
National Patient Advocate Foundation
Prevent Cancer Foundation
Friday, June 3, 2016
Thursday, June 2, 2016
US FDA Grants Orphan Drug Designation for Retrotope's RT001 in the Treatment of Friedreich's Ataxia
LOS ALTOS, CA -- (Marketwired) -- 06/01/16 -- Retrotope announced today that the U.S. Food and Drug Administration (FDA) Office of Orphan Products Development granted orphan drug designation for its stabilized fatty acid drug (RT001) for the treatment of Friedreich's ataxia (FA).
Wednesday, June 1, 2016
Epoetin Alpha Improves Upper-Limb Dexterity in Patients With Friedreich’s Ataxia: Presented at EAN
FirstWord Pharma, By Chris Berrie.
COPENHAGEN, Denmark -- May 31, 2016 -- Epoetin alpha does not modify frataxin levels or improve physical performance in patients with the debilitating, degenerative neuromuscular disorder known as Friedreich’s ataxia, although it progressively ameliorates upper-limb dexterity compared with placebo, according to results presented at the 2nd Congress of the European Academy of Neurology (EAN).
COPENHAGEN, Denmark -- May 31, 2016 -- Epoetin alpha does not modify frataxin levels or improve physical performance in patients with the debilitating, degenerative neuromuscular disorder known as Friedreich’s ataxia, although it progressively ameliorates upper-limb dexterity compared with placebo, according to results presented at the 2nd Congress of the European Academy of Neurology (EAN).
Tuesday, May 31, 2016
Paying for future success in gene therapy
Stuart H. Orkin, Philip Reilly. Science 27 May 2016: Vol. 352, Issue 6289, pp. 1059-1061 DOI: 10.1126/science.aaf4770
OPEN
The authors expect the federal Food and Drug Administration (FDA) will approve at least one gene therapy treatment within the next three years. As a new generation of gene therapy clinical trials shows promise to cure or halt the progression of several rare diseases, the time has come to explore ways to pay for the cutting edge treatments. Noting the potential of gene therapy to be a one-time treatment for rare and serious diseases that otherwise cost hundreds of thousands, if not millions, of dollars in chronic care over a lifetime. The process of developing a new gene therapy treatment and securing FDA approval, they estimate, entails about eight years and direct costs of hundreds of millions of dollars.
OPEN
The authors expect the federal Food and Drug Administration (FDA) will approve at least one gene therapy treatment within the next three years. As a new generation of gene therapy clinical trials shows promise to cure or halt the progression of several rare diseases, the time has come to explore ways to pay for the cutting edge treatments. Noting the potential of gene therapy to be a one-time treatment for rare and serious diseases that otherwise cost hundreds of thousands, if not millions, of dollars in chronic care over a lifetime. The process of developing a new gene therapy treatment and securing FDA approval, they estimate, entails about eight years and direct costs of hundreds of millions of dollars.
Monday, May 30, 2016
Uncovering brain-heart information through advanced signal and image processing.
Philos Trans A Math Phys Eng Sci. 2016 May 13; 374(2067): 20160020. doi: 10.1098/rsta.2016.0020
A recent article in Scientific American (‘A new idea for treating Alzheimer's’)begins with the following sentence: ‘If it's good for the heart, it could also be good for the neurons, astrocytes and oligodendrocytes, cells that make up the main items on the brain's parts list’, suggesting that Alzheimer's disease may be a candidate for combined brain–heart therapeutic approaches. Furthermore, a wide variety of changes in the electrocardiogram, mainly referring to arrhythmias and repolarization, is often observed in the context of neurological disease.
A significant part of the current knowledge on brain–heart interaction as applied to the medical field refers to ‘neurocardiology’. While this discipline is inherently multidimensional, it may be conceptualized as divided into three major categories: the heart's effects on the brain (e.g. cardiac source embolic stroke), the brain's effects on the heart (e.g. neurogenic heart disease) and neurocardiac syndromes (e.g. Friedreich's ataxia).
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
A recent article in Scientific American (‘A new idea for treating Alzheimer's’)begins with the following sentence: ‘If it's good for the heart, it could also be good for the neurons, astrocytes and oligodendrocytes, cells that make up the main items on the brain's parts list’, suggesting that Alzheimer's disease may be a candidate for combined brain–heart therapeutic approaches. Furthermore, a wide variety of changes in the electrocardiogram, mainly referring to arrhythmias and repolarization, is often observed in the context of neurological disease.
A significant part of the current knowledge on brain–heart interaction as applied to the medical field refers to ‘neurocardiology’. While this discipline is inherently multidimensional, it may be conceptualized as divided into three major categories: the heart's effects on the brain (e.g. cardiac source embolic stroke), the brain's effects on the heart (e.g. neurogenic heart disease) and neurocardiac syndromes (e.g. Friedreich's ataxia).
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
Sunday, May 29, 2016
Inside HDACs with more selective HDAC inhibitors
Joëlle Roche, Philippe Bertrand, European Journal of Medicinal Chemistry, Available online 25 May 2016, ISSN 0223-5234, doi: 10.1016/j.ejmech.2016.05.047.
Inhibitors of histone deacetylases (HDACs) are nowadays part of the therapeutic arsenal mainly against cancers, with four compounds approved by the Food and Drug Administration.During the last five years, several groups have made continuous efforts to improve this class of compounds, designing more selective compounds or compounds with multiple capacities. After a survey of the HDACs biology and structures, this review summarizes the results of the chemists working in this field, and highlights when possible the behaviour of the molecules inside their targets.
Associated disease: Friedreich's ataxia. Partners: Interacts with HDAC7 and HDAC9; DAXX, HDAC10 and DACH1; BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY, BTBD14B, GLIS2, NR2C1; CBFA2T3 and NKAP; APEX1, MAPK14, ZMYND15, SMRT/NCOR2 and BCL6, INSM1, XBP1 isoform 1, CCAR2, MEF2D, BEND3. Forms a heterologous complex at least with YY1, It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex. Component of the Notch corepressor complex. Functions: This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumour suppressor gene.
Inhibitors of histone deacetylases (HDACs) are nowadays part of the therapeutic arsenal mainly against cancers, with four compounds approved by the Food and Drug Administration.During the last five years, several groups have made continuous efforts to improve this class of compounds, designing more selective compounds or compounds with multiple capacities. After a survey of the HDACs biology and structures, this review summarizes the results of the chemists working in this field, and highlights when possible the behaviour of the molecules inside their targets.
Associated disease: Friedreich's ataxia. Partners: Interacts with HDAC7 and HDAC9; DAXX, HDAC10 and DACH1; BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY, BTBD14B, GLIS2, NR2C1; CBFA2T3 and NKAP; APEX1, MAPK14, ZMYND15, SMRT/NCOR2 and BCL6, INSM1, XBP1 isoform 1, CCAR2, MEF2D, BEND3. Forms a heterologous complex at least with YY1, It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex. Component of the Notch corepressor complex. Functions: This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumour suppressor gene.
Saturday, May 28, 2016
Mitochondrial energy imbalance and lipid peroxidation cause cell death in Friedreich’s ataxia
R Abeti, M H Parkinson, I P Hargreaves, P R Angelova, C Sandi, M A Pook, P Giunti and A Y Abramov. Cell Death and Disease (2016) 7, e2237; doi:10.1038/cddis.2016.111 Published online 26 May 2016
Open
Although the role of frataxin is largely known, being fundamental for the iron biogenesis in the cell, the relation between frataxin and mitochondrial bioenergetics is not completely clear.
We assessed the type of mitochondrial dysfunction that was present in the cerebellum, concluding that Complex I activity is impaired, but Complex II compensates by overworking. Therefore, if we consider the ETC, we can define the mitochondrial dysfunction as a mildly defective bioenergetic phenotype. However, this mild dysfunction drives the formation of free radicals that cannot be attenuated by the endogenous antioxidant systems, which are downregulated. Thus, the level of lipid peroxidation increases dramatically, damaging the cells and causing premature cell death. Therefore, lipid peroxidation could be a potential target for future therapeutic approaches in FRDA.
Open
Although the role of frataxin is largely known, being fundamental for the iron biogenesis in the cell, the relation between frataxin and mitochondrial bioenergetics is not completely clear.
We assessed the type of mitochondrial dysfunction that was present in the cerebellum, concluding that Complex I activity is impaired, but Complex II compensates by overworking. Therefore, if we consider the ETC, we can define the mitochondrial dysfunction as a mildly defective bioenergetic phenotype. However, this mild dysfunction drives the formation of free radicals that cannot be attenuated by the endogenous antioxidant systems, which are downregulated. Thus, the level of lipid peroxidation increases dramatically, damaging the cells and causing premature cell death. Therefore, lipid peroxidation could be a potential target for future therapeutic approaches in FRDA.
Friday, May 27, 2016
Mutations in the substrate binding glycine-rich loop of the mitochondrial processing peptidase-α protein (PMPCA) cause a severe mitochondrial disease
Mugdha Joshi, Irina Anselm, Jiahai Shi, Tejus A. Bale, Meghan Towne, Klaus Schmitz-Abe, Laura Crowley, Felix C. Giani, Shideh Kazerounian, Kyriacos Markianos, Hart G. Lidov, Rebecca Folkerth, Vijay G. Sankaran, and Pankaj B. Agrawal. Cold Spring Harb Mol Case Stud. 2016 May; 2(3): a000786. doi:10.1101/mcs.a000786
This study describes a severe mitochondrial disease due to PMPCA mutations in a large family, which we show is associated with altered levels of mature frataxin. Whereas a recent study described cerebellar ataxia as a presentation of PMPCA mutations, the phenotype in our family is more severe and typical of a mitochondrial disease. The observed phenotype may be related to impaired PMPCA function due to a reduction in its level and the resultant abnormal processing of frataxin and other mitochondrial proteins.
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
This study describes a severe mitochondrial disease due to PMPCA mutations in a large family, which we show is associated with altered levels of mature frataxin. Whereas a recent study described cerebellar ataxia as a presentation of PMPCA mutations, the phenotype in our family is more severe and typical of a mitochondrial disease. The observed phenotype may be related to impaired PMPCA function due to a reduction in its level and the resultant abnormal processing of frataxin and other mitochondrial proteins.
Open Access
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
Thursday, May 26, 2016
JOT101, a product for treatment of Friedreich’s ataxia.
Jupiter, Florida (PRWEB) May 25, 2016, by Christer Rosén, Jupiter Orphan Therapeutics.
Jupiter Orphan Therapeutics, Inc. (JOT) today announced that world renowned scientist David Sinclair, Ph.D. joined JOT as Co-Chairman of its Scientific Advisory Board (SAB).
Dr. Sinclair was contacted by his fellow scientists, Prof Martin Delatycki from Murdoch Childrens Research Institute, Australia (MCRI), who informed him of the resveratrol JOTROL product that was developed by JOT. JOT has a global license from MCRI regarding developing JOT101, a product for treatment of Friedreich’s ataxia.
Dr. Sinclair stated “I am excited about being able to work with JOT to bring drugs to patients who are waiting for a solution to their rare disease. JOTROL opens up the possibility that resveratrol will finally realize its potential to revolutionize human health.”
Jupiter Orphan Therapeutics, Inc. (JOT) today announced that world renowned scientist David Sinclair, Ph.D. joined JOT as Co-Chairman of its Scientific Advisory Board (SAB).
Dr. Sinclair was contacted by his fellow scientists, Prof Martin Delatycki from Murdoch Childrens Research Institute, Australia (MCRI), who informed him of the resveratrol JOTROL product that was developed by JOT. JOT has a global license from MCRI regarding developing JOT101, a product for treatment of Friedreich’s ataxia.
Dr. Sinclair stated “I am excited about being able to work with JOT to bring drugs to patients who are waiting for a solution to their rare disease. JOTROL opens up the possibility that resveratrol will finally realize its potential to revolutionize human health.”
Wednesday, May 25, 2016
Purkinje cell injury, structural plasticity and fusion in patients with Friedreich’s ataxia
Kevin C. Kemp, Amelia J. Cook, Juliana Redondo, Kathreena M. Kurian, Neil J. Scolding and Alastair Wilkins. Acta Neuropathologica CommunicationsNeuroscience of Disease20164:53. DOI: 10.1186/s40478-016-0326-3
For the first time in a genetic condition, we have also shown a disease-related increase in the frequency of Purkinje cell fusion and heterokaryon formation in Friedreich's ataxia cases; with evidence that underlying levels of cerebellar inflammation influence heterokaryon formation. Our results together further demonstrate the Purkinje cell’s unique plasticity and regenerative potential.
Understanding whether Purkinje cell axon remodelling and/or fusion represent mechanisms by which cerebellar functions can be maintained in genetic cerebellar disease has important therapeutic consequences. With the potential to protect and rescue neuronal cells and restore homeostatic balance during neurodegeneration, understanding the circumstances in which they occur may lead to techniques to manipulate these mechanisms therapeutically.
Open Access.
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
For the first time in a genetic condition, we have also shown a disease-related increase in the frequency of Purkinje cell fusion and heterokaryon formation in Friedreich's ataxia cases; with evidence that underlying levels of cerebellar inflammation influence heterokaryon formation. Our results together further demonstrate the Purkinje cell’s unique plasticity and regenerative potential.
Understanding whether Purkinje cell axon remodelling and/or fusion represent mechanisms by which cerebellar functions can be maintained in genetic cerebellar disease has important therapeutic consequences. With the potential to protect and rescue neuronal cells and restore homeostatic balance during neurodegeneration, understanding the circumstances in which they occur may lead to techniques to manipulate these mechanisms therapeutically.
Open Access.
This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)
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