Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies worldwide. Conventional pharmacological treatments primarily aimed at slowing the progression of degeneration have demonstrated limited long-term efficacy and often do not address the underlying causes of the disease. On the other hand, orthobiologics are regenerative agents derived from the patient’s own tissue and represent a promising emerging therapy for degenerative disc disease. This review comprehensively outlines the pathophysiology of DDD, highlighting the inadequacies of existing pharmacological therapies and detailing the potential of orthobiologic approaches. It explores advanced tools such as platelet-rich plasma and mesenchymal stem cells, providing a historical overview of their development within regenerative medicine, from foundational in vitro studies to preclinical animal models. Moreover, the manuscript delves into clinical trials that assess the effectiveness of these therapies in managing DDD. While the current clinical evidence is promising, it remains insufficient for routine clinical adoption due to limitations in study designs. The review emphasizes the need for further research to optimize these therapies for consistent and effective clinical outcomes, potentially revolutionizing the management of DDD and offering renewed hope for patients.

Alzheimer’s disease and Parkinson’s disease remain the most prevalent neurodegenerative disorders associated with aging and continue to lack curative treatments. Their pathophysiology is often multifaceted, encompassing protein aggregation, mitochondrial dysfunction, chronic neuroinflammation, synaptic degeneration, and vascular compromise. This complex landscape reduces the effectiveness of single-target pharmacological agents and underscores the need for therapies capable of acting across multiple axes. Orthobiologics and peptide-based strategies exemplify this approach. Autologous cellular alternatives such as platelet-rich plasma, bone marrow aspirates, mesenchymal stromal cell derivatives, and extracellular vesicles deliver paracrine signals that can reprogram glia, preserve mitochondrial function, and promote synaptic and vascular repair. Peptide therapeutics, including glucagon-like peptide-1 receptor agonists and novel sequences targeting protein aggregation or mitochondrial pathways, provide complementary precision by engaging defined receptors and intracellular cascades. Together, these modalities converge on mechanisms central to circuit preservation rather than symptomatic relief alone. Preclinical studies across Alzheimer’s and Parkinson’s disease demonstrate consistent neuroprotective and functional benefits, and early human trials support feasibility and safety. The translational path forward requires standardized preparation, biomarker integration, optimized delivery routes such as intranasal administration, and regulatory frameworks adapted to biologic therapies. This review synthesizes current evidence on orthobiologics and peptides in neurodegeneration, outlines safety and translational considerations, and highlights future directions, including rational combinations and biomarker-driven trials. By uniting the broad signaling capacity of orthobiologics with the precision of peptides, neurology can move beyond symptomatic care toward regenerative strategies that aim to preserve neural circuits and improve long-term outcomes in Alzheimer’s disease and Parkinson’s disease.

Degenerative disc disease (DDD) is a pervasive condition that limits quality of life and burdens economies. Traditional pharmacological treatments aimed at slowing degeneration are ineffective in the long-term. Orthobiologics, regenerative agents derived from the patient’s own tissue, are a promising emerging therapy for degenerative disc disease. This review first outlines the pathophysiology of degenerative disc disease, highlighting the limitations of existing treatments and explores the orthobiologic tools for treating degenerative disc disease (platelet-rich plasma, mesenchymal stem cells). Their history in regenerative medicine is outlined, demonstrating how in vitro evidence informed preclinical animal studies on their efficacy in treating degenerative disc disease. Finally, clinical trials utilizing these treatment options are reviewed and directions for future research are outlined. Although the current clinical evidence available is limited to propagate their routine clinical usage the field holds immense potential in the management of DDD. There is room for these treatments to be optimized for effective consistent clinical outcomes in DDD.