( ophos. In vitro TRO19622 promotes moto...)Trophos Publishes ALS Article in Journal of Pharmacology and,Experimental Therapeutics,Health

ophos. In vitro, TRO19622 promotes motor neuron survival in the absence of trophic support in a dose-dependent manner. In preclinical models in vivo, TRO19622 rescues motor neurons from axotomy-induced cell death in neonates and promotes nerve regeneration following sciatic nerve crush. Furthermore, in the SOD1G93A model of familial ALS, TRO19622 treatment improves motor performance, delays the onset of the clinical disease, and extends survival.

TRO19622 binds directly to two components of the mitochondrial permeability transition pore: the voltage-dependent anion channel (VDAC) and the translocator protein (or peripheral benzodiazepine receptor), suggesting a potential mechanism for its neuroprotective activity.

TRO19622 has successfully completed Phase I/Ib studies in both healthy volunteers and ALS patients demonstrating the product is well tolerated, has an excellent safety profile and that once-a-day dosing achieves the predicted exposure level required for efficacy, based on preclinical models. These data support the further clinical evaluation of TRO19622 as a potential treatment for ALS.

"Trophos is proud to have this body of work accepted for publication in a well recognized journal such as JPET," said Rebecca Pruss, CSO at Trophos. "Given the significant unmet medical need in ALS, it is tremendously encouraging that TRO19622 promotes the survival of motor neurons in this extensive battery of preclinical models. These studies, along with the excellent clinical safety profile of TRO19622, provide the basis upon which Trophos plans to initiate a pivotal Phase II/III trial to establish the clinical efficacy of TRO19622 in ALS patients."

Pruss added: "Moreover, we are particularly excited that there is increasing preclinical evidence that the mitochondria-mediated mechanism of action of TRO19622, and other compounds in this class, will have huge commercial potential in other chronic neurological disorders, such as neuropathic pain,
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