A Novel Reparative non-Opiod Therapy for Neuropathic Pain

Painful lumbar radiculopathy (PLR) and painful diabetic neuropathy (PDN) affect approximately 40 million patients in EU and US. Currently there is no registered drug for PLR and around  50% of patients with PDN are inadequately treated.

The pain associated with PLR and PDN originates from diseased sensory neurons that mediate sensations including pressure and heat from arms and legs to the spinal cord and brain. In PLR, a physical compression of the sensory nerves entering the spinal cord causes a pain known as sciatica, while the sensory neuropathy and pain in PDN are caused by metabolic injury. For both PLR and PDN there is a great medical need for tolerable therapies like NeuRepair that can protect, restore, and regenerate sensory neurons and thereby ameliorate the pain.

With its unique and reparative mechanism, NeuRepair is poised to become a first-in-class biotherapeutic and  has demonstrated  clinically meaningful  effects in both a phase I multi ascending dose study and in a multicenter phase IIa proof -of-concept study in chronic sciatica.  Encouraged by these positive clinical data we commence  further clinical development  in a multicenter phase IIb study in chronic sciatica and start a multicenter phase IIa study in PDN.

NeuRepair – How it Works

NeuRepair consists of a formulation of  the sensory survival and regenerative factor Neublastin (NBN). During the nervous system development, NBN supports the growth, differentiation, and function of sensory neurons. By readministering NBN in conditions of diseased sensory neurons, including PLR and PDN, we leverage the natural reparative mechanism of NBN to repair injured sensory neurons, restore sensory function, and to alleviate the pain.

NBN mediates signaling by binding to the GDNF  family receptor alpha 3 receptors (GFRalpha3), which are selectively expressed on sensory neurons. NBN can therefore be administered systemically to target sensory neurons in an effective and still selective manner.

NBN has demonstrated extraordinary therapeutic activity in multiple preclinical models of traumatic neuronal injury. Indeed, NBN has been shown to mediate neuroprotection, promote neuronal regeneration, and restore neuronal and tissue connectivity both at distal nerve endings and at the level of the spinal cord. NBN has also been demonstrated to normalize biomarkers of neuropathic pain.

Collectively these data indicate that NBN exhibits a great and broad spectrum of therapeutic activities and has the potential to become a transformational  treatment of  sciatica and PDN, as well as for other conditions of traumatic nerve injury and neuropathic pain.