APPB-429
Gene Therapy for Diabetic Peripheral Neuropathy
APPB-429 — Gene Therapy for Diabetic Peripheral Neuropathy
Disease-Modifying Gene Therapy Designed to Restore Peripheral Nerve Structure & Function
Developing a Disease-Modifying Gene Therapy Designed to Restore Peripheral Nerve Structure & Function
Diabetic Peripheral Neuropathy
Diabetic peripheral neuropathy (DPN) is one of the most common and debilitating complications of diabetes, affecting millions of people in the United States.
The disease results from progressive damage to peripheral nerves, particularly the long sensory nerves extending into the feet and lower extremities. Patients may experience burning pain, tingling, numbness, weakness, impaired balance, and progressive loss of sensation.
As DPN advances, loss of protective sensation can have serious consequences. Patients may become unable to feel injuries to their feet, contributing to diabetic foot ulceration, infection, hospitalization, and lower-extremity amputation.
Despite the enormous burden of the disease, current pharmacologic treatments primarily focus on managing symptoms such as neuropathic pain. There is currently no established FDA-approved therapy demonstrated to regenerate lost peripheral nerve fibers and reverse the underlying structural neuropathy of DPN.
A Different Therapeutic Approach
APPB-429 is an investigational gene therapy program being developed to address the underlying biology of diabetic peripheral neuropathy.
DPN is not simply a pain disorder. The disease involves progressive injury to peripheral nerve fibers together with disruption of the biological environment required to maintain healthy nerve function and support natural nerve repair.
APPB-429 is being designed to deliver sustained regenerative and protective biological signals within the affected lower extremity, with the objective of creating an environment that supports peripheral nerve repair and restoration of nerve function.
Rather than developing another therapy focused primarily on reducing neuropathic pain, the APPB-429 program is focused on disease modification and peripheral nerve regeneration.
Local Gene Therapy
APPB-429 is being developed as a locally administered gene therapy.
The therapeutic strategy is designed to enable cells within the treated lower extremity to produce selected naturally occurring human proteins involved in regenerative, neurotrophic, and protective biological signaling.
By generating these therapeutic signals locally, APPB-429 is intended to provide sustained biological activity in the region affected by peripheral neuropathy while limiting unnecessary systemic exposure.
The Company’s preclinical development program is evaluating therapeutic combinations designed to address multiple components of DPN biology, including peripheral nerve degeneration, impaired regenerative signaling, neuroinflammation, and disruption of the local environment supporting healthy nerve function.
Restoring Nerve Function
Peripheral nerves possess an inherent capacity for regeneration. In diabetes, however, the biological environment necessary for successful nerve repair becomes progressively impaired.
The APPB-429 program is based on the hypothesis that restoring this environment may allow damaged peripheral nerves to repair and regenerate.
The Company’s development strategy is therefore focused on demonstrating both structural nerve regeneration and recovery of nerve function.
If successful, this approach could represent a fundamentally different treatment paradigm for diabetic peripheral neuropathy: restoring damaged peripheral nerves rather than simply managing the symptoms caused by their degeneration.
Preclinical Development
Applied Biologics is currently advancing the preclinical development of APPB-429, including evaluation of therapeutic gene combinations and local gene-delivery strategies.
The program is being developed toward selection of a lead therapeutic candidate and subsequent IND-enabling development for clinical evaluation in patients with diabetic peripheral neuropathy.
APPB-429 is an investigational development program. APPB-429 has not been approved by the U.S. Food and Drug Administration, and its safety and efficacy have not been established.