Novel Epigenetic Techniques Provided by the CRISPR/Cas9 System.

Nina Xie, Yafang Zhou, Qiying Sun, and Beisha Tang, Stem Cells International, vol. 2018, Article ID 7834175, 12 pages, 2018. doi:10.1155/2018/7834175.

Other representative candidates may include the Rett syndrome, Huntington’s disease, and Friedreich ataxia, where dCas9-epieffector complex may be harnessed to restore or repress the responsible gene to cure the disease.

In conclusion, all of the studies described above indicated that CRISPR/Cas9-mediated epigenome editing holds a great promise for epigenetic studies and therapeutics. However, there are still some limitations to be scrutinized. First of all, in terms of basic science studies, although most studies claimed high specificity in their experiments, however, the high specificity usually is the result of repeated optimization. A precise model that could predict deleterious off-target effects during the experiment design stage is still lacking. In addition, although transactivation or repression effects on multiple genes were well documented in publications, mechanisms underlying the phenomenon were not clear. Epigenetic mark profiling on epigenome scale was not sufficient. Local CHIP-seq data usually only focused on the characterization of one or few histone marks. Theoretically, we hope that epigenome editing could achieve targeted gene regulation by changing epigenetic marks specifically and freely according to our wills. To achieve this goal, high specificity and clarified mechanisms are the prerequisite. Therefore, more thorough off-target event assessments and more studies focusing on mechanisms underlying epigenome editing are needed.

Moreover, in terms of clinical applications, several issues need to be addressed prior to successful clinical translation. Firstly, the endurance of gene activation or a repression effect mediated by CRISPR/Cas9 remains to be undetermined. It has been thought that epigenome-editing-induced gene activation or repression is short-term. On the contrary, there was also evidence showing that a gene silencing effect mediated by the hit-and-run epigenome editing strategy could also be long-term and inheritable. A short-term effect is more suitable for antagonizing acute pathogenic factor exposure and the transdifferentiation process. However, for treating chronic diseases, a long-term effect is expected. Additionally, a safer and efficient delivery method should be developed [92]. Adeno-associated virus (AAV) vectors have been the prevailing delivery method for some time. By tagging a synthetic surface peptide, splitting the Cas9 protein or using its smaller orthologues, and choosing a suitable administration route, researchers significantly improved the packaging capacity and delivery efficiency of AAV vectors. However, for clinical applications, more optimization is required. The immunogenicity of AAV vectors, dCas9 proteins, and guide RNAs should be determined precisely. The off-target effects of AAV vectors or dCas9-epieffector complex should be minimized as much as possible to ensure clinical safety.

Company hopes to speed up payments for clinical trial patients

(Action News) KING OF PRUSSIA, Pa. Wednesday, August 22, 2018
Clinical trials help drive medical advances. However, some patients hedge at taking part because reimbursement for their expenses take time.

Two years ago, Kyle took part in a test of ClinCard, a reloadable debit card. Once a patient's ClinCard is established, money is loaded after each research visit... no check, no cash. It's instant money for the patient, and instant documentation for the trial site.

PTC Therapeutics Successfully Completes Acquisition of Agilis Biotherapeutics

SOUTH PLAINFIELD, N.J., Aug. 23, 2018 /PRNewswire/ -- PTC Therapeutics, Inc. (NASDAQ: PTCT), today announced that it has successfully completed the acquisition of Agilis Biotherapeutics, Inc., a private biotechnology company focused on the advancement of innovative gene therapy programs for rare genetic disorders that affect the central nervous system (CNS).
The acquisition also includes gene therapy programs in development, GT-FA, GT-AS, and GT-RLN, for Friedreich Ataxia, Angelman Syndrome and Cognitive Disorders associated with several neurodevelopmental and neurodegenerative disorders, respectively.

Longitudinal Diffusion Tensor Imaging in the brain in Friedreich’s Ataxia: follow-up at 12 and 24 months

Pierre-Gilles Henry, James Joers, Dinesh Deelchand, Diane Hutter, and Christophe Lenglet; International Society for Magnetic Resonance in Medicine, (Abstract #3730) 16-21 June 2018

We report 12-month and 24-month longitudinal diffusion tensor imaging (DTI) data in the brain of subjects with Friedreich’s ataxia (FRDA). Significant longitudinal changes were observed in several brain areas (including the corpus callosum, internal capsule and superior corona radiata) in a group of 13 patients over 24 months. Our data suggest that diffusion MRI of the brain could be useful to better understand the impact of FRDA on brain microstructure and connectivity, and to assess the effect of potential treatments on neurodegeneration in upcoming clinical trials in FRDA.

Noninvasive brain stimulation may help treat symptoms of rare movement disorders

August 22, 2018, American Academy of Neurology.
Electrical stimulation of the brain and spinal cord may help treat the symptoms of rare movement disorders called neurodegenerative ataxias, according to a study published in the August 22, 2018, online issue of Neurology, the medical journal of the American Academy of Neurology. There are several types of these disorders, which can be hereditary or occur randomly, including spinocerebellar ataxia, multiple system atrophy and Friedreich's ataxia.

Public summary of opinion on orphan designation: Omaveloxolone for treatment of Friedreich's ataxia

EMA/395368/2018, 16 August 2018

On 27 June 2018, orphan designation (EU/3/18/2037) was granted by the European Commission to Dr Stefan Blesse, Germany, for omaveloxolone (also known as RTA 408) for the treatment of Friedreich’s ataxia.
In accordance with Regulation (EC) No 141/2000 of 16 December 1999, the COMP adopted a positive opinion on 24 May 2018 recommending the granting of this designation.

Jupiter Orphan Therapeutics Announces Favorable Data Which Expands JOTROL's Applications to the Estimated $5 Billion Mitochondrial Rare Disease Market

JUPITER, Fla., Aug. 22, 2018 /PRNewswire/ -- Jupiter Orphan Therapeutics, Inc. ("JOT"), Jupiter, FL, today announced that it has received new data regarding an increase in mitochondrial biogenesis in liver and brain from a recently performed study in a frequently studied Alzheimer's disease animal model, the triple transgenic (APPsw / PS1M146V / TauP301L) mouse.

Murdoch Children's Research Institute, a JOT partner, has conducted an open label study showing that high dose of resveratrol (not JOTROL), with associated GI-side effects, had significant positive impact in 4 vital endpoints. Target, for this indication, is to reproduce this study with JOTROL and reproduce the same positive results without side effects.

Test-retest reliability of an instrumented electronic walkway system (GAITRite) for the measurement of spatio-temporal gait parameters in young patients with Friedreich’s ataxia

Bastien Roche, Anne-Laure Simon, Sophie Guilmin-Crépon, Priscilla Boizeau, Béatrice Andriss, Corinne Alberti, Ana Presedo, Brice Ilharreborde, Isabelle Husson, Gait & Posture, 2018, doi:10.1016/j.gaitpost.2018.08.017.

The GAITRite system allows feasible and reliable measurements of gait parameters in young patients with FRDA. Lower reliability found for the weakest parameters was attributed to the software automatic errors and the ankle laxity noted in every patient.

Investigating Molecular Mechanisms Underlying Mild Phenotype in Friedreich Ataxia Patients with G130V Missense Mutation

Clark, Elisia. University of Pennsylvania, ProQuest Dissertations Publishing, 2018. 10748306. A DISSERTATION in Pharmacology Presented to the Faculties of the University of Pennsylvania in Partial Ful fillment of the Requirements for the Degree of Doctor of Philosophy.

Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase

Hinman A, Holst CR, Latham JC, Bruegger JJ, Ulas G, McCusker KP, et al. (2018) Vitamin E hydroquinone is an endogenous regulator of ferroptosis via redox control of 15-lipoxygenase. PLoS ONE 13(8): e0201369. https://doi.org/10.1371/journal.pone.0201369