BioBlast Pharma Ltd., a clinical-stage orphan disease-focused biotechnology company, announced positive preclinical in vitro and in vivo proof-of-concept study results for its Read-through drug candidate, BBrm02 for spinal muscular atrophy (SMA). BBrm02 is a proprietary, intrathecal formulation of azithromycin.

In a series of cell and mouse studies BBrm02 was effective in creating high levels of full length SMN2 protein (Survival Motor Neuron 2) in the central nervous system resulting in a high degree of cellular and disease phenotypic rescues. Significant levels of full length SMN2 protein were detected following treatment with BBrm02 in several different patient cell lines representing different stages of disease severity. This SMN2 protein was tested for biological activity and was found to be highly functional.

In two different mouse models of spinal muscular atrophy, BBrm02 was effective in preventing weight loss, increasing animal survival, and in normalizing a range of neurological functions, including, among others, the ability of the mouse to return to four feet from a supine position (time-to-right test) and to walk on a narrow tube (tube-test), both of which measure equilibrium and muscle strength.

Colin Foster, BioBlast’s president and chief executive officer, commented “We are excited to share this comprehensive proof-of-concept as it establishes the efficacy of our lead drug candidate in our Read-through platform for spinal muscular atrophy. Importantly, given that BBrm02 is a repurposed drug (azithromycin), we believe there is a reasonable possibility for a shorter developmental process. We plan to start a phase 2a study with BBrm02 by year-end, 2015.”

Foster also noted that there are no drugs approved today for SMA, which is an orphan disease with approximately 30,000 patients in the US and an equal number in Europe.

BBrm is BioBlast’s family of small molecule non-glycoside, repurposed drugs for the treatment of patients with genetic disorders that arise from a type of genetic mutation known as a nonsense mutation (stop codon). The platform enables the read-through (deactivation) of the genetic defects that stop synthesis of proteins called stop codons. Deactivation of a disease-causing nonsense mutation can alleviate the symptoms of the corresponding genetic disease.

SMA is the leading genetic cause of infant mortality and is caused by the loss of a functional Survival Motor Neuron 1 protein (SMN1). The disease is manifested by loss of muscle mass and mobility as well as severe compromises related to vital functions such as respiration. Another protein called SMN2 (Survival Motor Neuron 2) is a nearly identical copy of SMN1, differentiated only by a silent, single-nucleotide mutation within the DNA. SMN2 partially compensates for the dysfunction of SMN1, however, the small amount of the functional protein that is produced from the SMN2 gene is not able to fully compensate for the loss of SMN1. Prior independent studies proposed that read-through agents, such as aminoglycosides, could induce the read-through of the stop codon located in the SMN2 gene, thus elongating the SMN2 and creating a full length functional protein that can compensate for the non-functioning SMN1, thereby alleviating the disease.