Launches of First Therapies Approved for Spinal Muscular Atrophy and Friedreich's Ataxia Will Revolutionize Treatment and Drive Growth of These Rare Disease Markets

BURLINGTON, Mass., Oct. 25, 2016 /PRNewswire/ -- Decision Resources Group finds that the anticipated launches of the first therapies for the treatment of spinal muscular atrophy (SMA) or Friedreich's ataxia (FA) will transform treatment of these diseases and lead to their markets expanding dramatically.
Following the anticipated label expansion of Horizon Pharma's Actimmune (interferon gamma-1b), the FA market is forecasted to grow significantly over the next ten years. However, interviewed neurologists' perceived limitations of Actimmune, including its unclear mechanism of action, variable effect on frataxin protein levels, and modest preservation of neurological function, could constrain its uptake and allow competitors to challenge Actimmune's position.
According to interviewed experts, gene therapy will also transform the FA treatment landscape, possibly negating the need for drug treatment. However, gene therapies being developed by Agilis Biotherapeutics, Pfizer, and RaNA Therapeutics are in preclinical testing and unlikely to launch during the study period.
"Despite the lack of competing brands entering the market in the near term, Actimmune's high U.S. cost may be an obstacle for its rapid adoption among patients with FA. If Actimmune can show that it delays disease progression or improves neurological function over a year or more, prescribers, patients, and payers are likely to accept its very high price."

Disruption of Higher Order DNA Structures in Friedreich’s Ataxia (GAA)n Repeats by PNA or LNA Targeting

Helen Bergquist, Cristina S. J. Rocha, Rubén Álvarez-Asencio, Chi-Hung Nguyen, Mark. W. Rutland, C. I. Edvard Smith, Liam Good, Peter E. Nielsen, Rula Zain; PLoS ONE 11(11): e0165788. doi:10.1371/journal.pone.0165788

Chemical and structural probing of GAA repeats provides evidence for pyrimidine triplex (H-DNA) formation and the presence of different structures at the pathological repeats. Furthermore, we find that PNA and LNA sequence-specific targeting of Friedreich’s ataxia GAA repeat expansions can alter and resolve higher order DNA structures. BQQ-OP mediated triplex-specific cleavage of double strand DNA and chloroacetaldehyde chemical modification of single strand DNA regions at (GAA)n repeats demonstrate that GAA-PNA binding result in a duplex invasion complex, that completely dissociates all detectable triplex containing higher order structures at this site, whereas this is not the case for CTT-PNA. Additionally, we obtained a similar pattern using LNA based ONs. Furthermore, a significant change in plasmid morphology in the presence of GAA-LNA was detected using atomic force microscopy. Our results suggest that DNA targeting by modified GAA-oligomers at expanded (GAA)n repeats can be employed to examine the possible role of non-canonical DNA structures in FXN gene silencing and potentially applied to develop new nucleic acids-based therapeutic strategies in Friedreich’s ataxia disease.