A new case of complete primary cerebellar agenesis: clinical and imaging findings in a living patient

Feng Yu, Qing-jun Jiang, Xi-yan Sun, Rong-wei Zhang; Brain, Volume 138, Issue 6, 1 June 2015 DOI:10.1093/brain/awu239

DON’T mind the gap. A woman has reached the age of 24 without anyone realising she was missing a large part of her brain. The case highlights just how adaptable the organ is. Woman of 24 found to have no cerebellum in her brain, however, in this woman, the missing cerebellum resulted in only mild to moderate motor deficiency, and mild speech problems such as slightly slurred pronunciation. Her doctors describe these effects as “less than would be expected”, and say her case highlights the remarkable plasticity of the brain.

Cerebellar agenesis is an extremely rare condition implying complete absence of the cerebellum.

Otoneurological Abnormalities in Patients with Friedreich's Ataxia

Zeigelboim BS, Mesti JC, Fonseca VR, Faryniuk JH, Marques JM, Cardoso RC, Teive HA. Int Arch Otorhinolaryngol. 2017 Jan;21(1):79-85. doi: 10.1055/s-0036-1572529.

The most prevalent otoneurological symptoms were incoordination of movement, gait imbalance, and dizziness. Alterations in the vestibular examination occurred in 90% of patients, located mainly in the caloric test, with a predominance of deficient central vestibular system dysfunction.

The study emphasizes the importance of the vestibular evaluation for the topographic diagnosis of neurodegenerative diseases since, in most cases, the otoneurological symptoms present early and such information may aid in the choice of procedures to be performed in clinical and therapeutic monitoring.

Synthetic genome readers target clustered binding sites across diverse chromatin states

Graham S. Erwin, Matthew P. Grieshop, Devesh Bhimsaria, Truman J. Do, José A. Rodríguez-Martínez, Charu Mehta, Kanika Khanna, Scott A. Swanson, Ron Stewart, James A. Thomson, Parameswaran Ramanathan, and Aseem Z. Ansari; PNAS 2016 113 (47) E7418-E7427; published ahead of print November 8, 2016, doi: 10.1073/pnas.1604847113

The linear polyamide (3) studied here was designed to bind to GAA repeats in the first intron of frataxin, a locus that appears to be situated within heterochromatin marked by H3K9me3. Taken together, the ability of polyamides to access heterochromatin (a major barrier to binding to natural and artificial DNA-binding factors) opens unique opportunities to deploy this class of synthetic genome readers to regulate gene networks that direct cellular fate and function. Linear 3, designed to target 5′-AAGAAGAAG-3′, is designed to target a GAA repeat expansion found in patients with Friedreich’s ataxia to alleviate transcriptional repression.
The COSMIC-seq approach that we describe here is a robust and broadly applicable method that can be readily extended to map the genome-wide binding properties of other classes of DNAbinding molecules, including several genome-directed therapeutics. COSMIC-seq will be instrumental in the genome-guided design of molecules that serve as precision-targeted therapeutics.

A wearable proprioceptive stabilizer for rehabilitation of limb and gait ataxia in hereditary cerebellar ataxias: a pilot open-labeled study

Luca Leonardi, Maria Gabriella Aceto, Christian Marcotulli, Giuseppe Arcuria, Mariano Serrao, Francesco Pierelli, Paolo Paone, Alessandro Filla, Alessandro Roca, Carlo Casali. Neurol Sci (2016). First Online: 31 December 2016 doi:10.1007/s10072-016-2800-x

The aim of this pilot study is to test the feasibility and effectiveness of a wearable proprioceptive stabilizer that emits focal mechanical vibrations in patients affected by hereditary cerebellar ataxias. This small open-labeled study shows preliminary evidence that focal mechanical vibration exerted by a wearable proprioceptive stabilizer might improve limb and gait ataxia in patients affected by hereditary cerebellar ataxias.

CN Project OPUS10: “Role of microRNAs in regulation iron metabolism in Friedreich's ataxia”

biotechnologia.pl; Prof. Włodzimierz Krzyżosiak, Institute of Bioorganic Chemistry PAS, Polish Academy of Sciences.(2017-01-02)

The goals of this project are to define changes in the expression and activity of microRNAs in FRDA, and analyze how these abnormalities affect the activity of genes which are responsible for the localization and amount of iron in neuronal and heart cells of patients with Friedreich’s ataxia. We will define relationship between miRNA molecules and iron availability. We will also uncover the pattern of detectable microRNA molecules that is specific to FRDA.

Percutaneous needle tenotomy for the treatment of muscle and tendon contractures in adults with brain damage: results and complications

Flavia Coroian, Claire Jourdan, Jérome Froger, Claire Anquetil, Olivier Choquet, Bertand Coulet, Isabelle Laffont, Archives of Physical Medicine and Rehabilitation, Available online 18 December 2016, ISSN 0003-9993, doi:10.1016/j.apmr.2016.11.014.

In our series, percutaneous needle tenotomy procedures under local or locoregional anesthesia were performed by a PM&R physician trained by an orthopedic surgeon and yielded very few complications. This technique seems relevant for contractures of several superficial tendons for the upper and lower limb alike. Furthermore, this technique gives a satisfactory orthopedic outcome fulfilling non-functional objectives (hygiene, pain, nursing) and even functional ones for a small number of well-selected patients (gait, grip, daily life).
PNT yields good results in the management of superficial muscle and tendon contractures in selected brain-damaged patients. The complications rate is very low and this treatment can be an alternative to conventional surgery in frail neurological patients.

Gene therapy: Gene-editing therapy for neurological disease

Moira A. McMahon & Don W. Cleveland. Nature Reviews Neurology 13, 7–9 (2017) doi:10.1038/nrneurol.2016.190 Published online 16 December 2016.

Guide RNA-mediated CRISPR–Cas nucleases are a powerful technology for the engineering of mammalian genomes. CRISPR–Cas9-dependent editing of mutated genes that cause Huntington disease and fragile X syndrome was recently achieved in cell-based models, heralding the first step towards developing this technology into viable therapeutics for neurological diseases.
The successful translation of these proof‑of‑principle studies to in vivo gene editing is eagerly anticipated, but several challenges remain. One major challenge is delivery of the sgRNA and nuclease to target cells. A final major challenge for extension of gene-editing approaches to applications within the nervous system is the efficiency of gene silencing or correction: can the changes be made in sufficient numbers of cells to alter the disease course?.
What seems certain is that continued development of genome-editing technology to target neurological diseases is likely to provide a greater understanding of the diseases themselves and, hopefully, will one day form the basis of a successful therapy.

Clinical trials: To catch a crook, you might try statistics

Gary R. Cutter; Nature Reviews Neurology 13, 9–10 (2017) doi:10.1038/nrneurol.2016.194 Published online 16 December 2016

To reduce research fraud, we need to understand more deeply why professional researchers and clinicians commit fraud. Certainly, personal interest is a major factor. Review boards thoroughly assess conflicts of interest to protect authors from gaining excess monetary gains via publications, but we have little to protect against advancing one’s personal interests — indeed, we reward it. Promotions, grants and grant renewals all depend on publications. Moreover, researchers might commit fraud for more egotistic reasons than mere survival in their chosen career, such as for money or to get a product on the market, to boost the market value of their start‑up company, or perhaps even to deliberately sabotage competitors.
Making trial and other experimental data publicly available have been suggested as one
strategy to reduce fraud, as any interested individual could search for evidence, thereby making fraud less tempting. However, the consequences of the false positives should be kept in mind: do we wish to impugn even one honest researcher in our attempts to catch dishonest ones?.

Single Protein May Hold Secret to Treating Parkinson’s Disease and More

By Dana G. Smith, PhD / Gladstone News / December 26, 2016.

“Nrf2 coordinates a whole program of gene expression, but we didn’t know how important it was for regulating protein levels until now,” explained first author Gaia Skibinski, PhD, a staff research scientist at Gladstone. “Overexpressing Nrf2 in cellular models of Parkinson’s disease resulted in a huge effect. In fact, it protects cells against the disease better than anything else we’ve found.”

The scientists say that Nrf2 itself may be difficult to target with a drug because it is involved in so many cellular processes, so they are now focusing on some of its downstream effects. They hope to identify other players in the protein regulation pathway that interact with Nrf2 to improve cell health and that may be easier to drug.

Synthetic genome readers target clustered binding sites across diverse chromatin states

Graham S. Erwin, Matthew P. Grieshop, Devesh Bhimsaria, Truman J. Do, José A. Rodríguez-Martínez, Charu Mehta, Kanika Khanna, Scott A. Swanson, Ron Stewart, James A. Thomson, Parameswaran Ramanathan, and Aseem Z. Ansari, PNAS 2016 ; published ahead of print November 8, 2016, doi: 10.1073/pnas.1604847113

Nucleosomal DNA, even in heterochromatin, may thus be partially preorganized to accommodate polyamide binding in the minor groove. The linear polyamide (3) studied here was designed to bind to GAA repeats in the first intron of frataxin to alleviate transcriptional repression, a locus that appears to be situated within heterochromatin marked by H3K9me3. Taken together, the ability of polyamides to access heterochromatin (a major barrier to binding to natural and artificial DNA-binding factors) opens unique opportunities to deploy this class of synthetic genome readers to regulate gene networks that direct cellular fate and function.