Treatments for neurological disorders

Inventors

Rossomando, Anthony • Porreca, Frank • Sah, Dinah Wen-Yee

Assignees

Sinfonia Biotherapeutics AB • University of Arizona

Abstract

Disclosed are methods of improving impaired proprioception, treating brachial plexus injuries, regenerating large and small nerve fibers, treating dorsal root nerve injuries, and improving sensory neural responses in a subject by administration of a neublastin polypeptide.

Core Innovation

The invention relates to using neublastin polypeptides, which are artemin/enovin polypeptides that are dimerized to bind a complex containing GFR1 and RET. The described approach is directed to treating an impairment or loss of sensory function associated with damage to or loss of sensory nerve fibers in a human subject. The polypeptide is defined by specific amino acid segments corresponding to amino acids 15-113 of SEQ ID NO:1 and related SEQ ID variants.

The method results in regeneration of sensory nerve fibers and in a persistent restoration of sensory function. The patent describes administering the dimerized polypeptide within a defined post-damage period, including an administration window within one month following the damage to or loss of nerve fibers. The document further states that treatment timing and dosing windows can affect different aspects of recovery, including thermal versus mechanical recovery.

The described neublastin polypeptides are presented as capable of producing long-lasting functional outcomes, including persistent sensory and sensorimotor recovery. The patent summarizes that the polypeptide promotes regeneration in the peripheral nerve context and supports continued functional restoration following nerve injury. The document also reports that neublastin does not alter DREZ inhibitory barrier markers, while preserving relevant sensory pathway responses and supporting axon reentry through the DREZ.

Claims Coverage

The independent claim covers regenerating sensory nerve fibers with persistent restoration of sensory function in a human subject by administering a specific dimerizable neublastin polypeptide variant that binds a GFR1/RET ternary complex, with administration constrained to occur within one month after nerve-fiber damage or loss. Dependent claims further refine timing, injury context, administration route, and the polypeptide variant choice.

Across the independent claim, the core inventive concept is regeneration of sensory nerve fibers with persistent sensory-function restoration by administering a dimerizable neublastin polypeptide defined by amino acids 15-113 from specified SEQ IDs, where the dimer binds a GFR1/RET-containing complex, and the administration is performed within one month after nerve-fiber damage or loss.

Stated Advantages

Documented Applications