Combined Cerebellar Proton MR Spectroscopy and DWI Study of Patients with Friedreich’s Ataxia

Laura Ludovica Gramegna, Caterina Tonon , David Neil Manners, Antonella Pini, Rita Rinaldi, Stefano Zanigni, Claudio Bianchini, Stefania Evangelisti, Filippo Fortuna, Valerio Carelli, Claudia Testa, Raffaele Lodi; The Cerebellum pp 1-7, First online: 20 February 2016 DOI: 10.1007/s12311-016-0767-z

The correlation between NAA/Cr and the severity of disability suggests that this biochemical in vivo MR parameter might be a useful biomarker to evaluate therapeutic interventions.

CNS Drug Delivery: Beyond the Spinal Cord

Recently the intrathecal administration has been proposed as part of a hopeful therapy for FA (Intrathecal delivery of frataxin mRNA encapsulated in lipid nanoparticles to dorsal root ganglia as a potential therapeutic for Friedreich’s ataxia). This paper shows (in laboratory animals) the feasibility of the use of intrathecal administration to reach efficiently the dorsal root ganglia.

This presentation explains the current state of the art in other neurological diseases in which it is required reach the CNS.

Mission: Improve outcomes for epileptic patients who don’t respond to conventional treatments by administering reformulated, micro-doses of anti-epileptic drugs directly to the brain.

Retrotope Advances RT001 in Clinical Trials to Treat Friedreich's ataxia

(Ref: Marketwired) February 22nd, 2016

LOS ALTOS, CA--(Marketwired) - Retrotope, a privately held clinical stage pharmaceutical company, today announced the successful completion of the first dose cohort and the opening of patient enrollment for the highest dose cohort in its ongoing 28-day study of orally dosed RT001 in Friedreich's ataxia (FA) patients. RT001 was well tolerated and no serious adverse events or dose limiting toxicities were observed.

Long-term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia

Saccà, F., Puorro, G., Marsili, A., Antenora, A., Pane, C., Casali, C., Marcotulli, C., Defazio, G., Liuzzi, D., Tatillo, C., Cambriglia, D. M., Schiano di Cola, G., Giuliani, L., Guardasole, V., Salzano, A., Ruvolo, A., De Rosa, A., Cittadini, A., De Michele, G. and Filla, A. (2016), Long-term effect of epoetin alfa on clinical and biochemical markers in friedreich ataxia. Mov. Disord.. doi: 10.1002/mds.26552

Although results are not in favor of an effect of epoetin alfa in Friedreich ataxia, this is the largest trial testing its effect. It is still possible that epoetin alfa may show some symptomatic effect on upper-limb performance. This study provides class I evidence that erythropoietin does not ameliorate VO2 max in patients with Friedreich ataxia.

Reversal of epigenetic promoter silencing in Friedreich ataxia by a class I histone deacetylase inhibitor

Yogesh K. Chutake, Christina C. Lam, Whitney N. Costello, Michael P. Anderson and Sanjay I. Bidichandani; Nucl. Acids Res. (2016) doi: 10.1093/nar/gkw107 First published online: February 20, 2016

OPEN

We conclude that repeat-mediated epigenetic promoter silencing in FRDA is mediated by class I HDACs, and it is reversible via treatment with specific inhibitors. It is noteworthy that the correction of both the structural and functional defects of the FXN promoter in FRDA, albeit partial, occurs in its natural genomic context, i.e. while in continued physical proximity to the cis-acting expanded GAA-TR sequence. These features bode well for the development of class I HDAC inhibitors as a rational therapeutic modality for FRDA.

UNC gene therapy spinout Bamboo Therapeutics raises $49.5M Series A

Startups, Biotech, By Meghana Keshavan http://medcitynews.com.

The startup’s developing gene therapies for rare neurologic diseases, which include Giant axonal neuropathy (GAN), Canavan disease, Friedreich’s ataxia as well as Duchenne muscular dystrophy. Bamboo’s most advanced program is its therapeutic for GAN, which is currently in Phase 1/2 trials. CBS News ran a piece on Bamboo’s approach to GAN in October.

Agilis Biotherapeutics and Waisman Biomanufacturing Enter Into Exclusive Manufacturing Agreement for Friedreich’s Ataxia Gene Therapy

February 18, 2016,  CAMBRIDGE, Mass. & MADISON, Wis.--(BUSINESS WIRE)--Agilis Biotherapeutics, LLC (Agilis), a biotechnology company advancing innovative gene therapies for rare genetic diseases that affect the central nervous system (CNS), and Waisman Biomanufacturing, a non-profit gene and cell therapy development and manufacturing group located at the UW-Madison Waisman Center, (Waisman) announced today that the companies have entered into an exclusive partnership agreement for the production of Agilis’ novel gene therapy product, AGIL-FA, for the treatment of Friedreich’s ataxia (FA).

Intrathecal delivery of frataxin mRNA encapsulated in lipid nanoparticles to dorsal root ganglia as a potential therapeutic for Friedreich’s ataxia

Joseph F. Nabhan, Kristy M. Wood, Varada P. Rao, Jeffrey Morin, Surya Bhamidipaty, Timothy P. LaBranche, Renea L. Gooch, Fazli Bozal, Christine E. Bulawa & Braydon C. Guild; Nature, Scientific Reports 6, Article number: 20019 (2016) doi:10.1038/srep20019

OPEN

When FXN LNPs were delivered by intrathecal administration, we detected recombinant human FXN protein in DRG. These observations provide the first demonstration that RTT can be used for the delivery of therapeutic mRNA to DRG.
Remarkably, greater than 50% mFXN protein derived from LNPs was detected seven days after intravenous administration of FXN LNPs, suggesting that the half-life of mFXN in vivo exceeds one week.

Understanding the Role of Mitochondrial Pathophysiology in Friedreich's Ataxia

Rosella Abeti, Michael H. Parkinson, Iain P. Hargreaves, Mark A. Pook, Andrey Y. Abramov, Paola Giunti, Biophysical Journal, Volume 110, Issue 3, Supplement 1, 16 February 2016, Page 474a, ISSN 0006-3495, doi:10.1016/j.bpj.2015.11.2534.

By using functional microscopy and biochemical techniques we were able to demonstrate that mitochondria are deregulated in neurons from the FRDA mouse models.

Scientists find potential treatment for Friedreich’s ataxia

UT Southwestern, Newsroom. DALLAS – Feb. 16, 2016 – Researchers at UT Southwestern Medical Center have identified synthetic RNA and DNA that reverses the protein deficiency causing Friedreich’s ataxia, a neurological disease for which there is currently no cure.