Onvansertib Combination Therapy for Non-Adrenergic BPH Contraction
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Solution Overview
Problem
Current medical treatments for benign prostatic hyperplasia (BPH) have limited effectiveness in reducing lower urinary tract symptoms, with α1-blockers providing only modest symptom relief and 5α-reductase inhibitors offering limited prostate size reduction, leading to high discontinuation rates and potential disease progression.
Innovation Solution
Combining the highly selective polo-like kinase 1 (PLK1) inhibitor, onvansertib, with α1-blockers to inhibit both adrenergic and non-adrenergic smooth muscle contractions in the prostate, thereby enhancing symptom relief and reducing prostate growth.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If α1-blockers are used to treat BPH, then prostate smooth muscle contraction is inhibited, but symptom relief is only modest (not more than 50% improvement)
Solution Approach 1:
The invention segments the treatment approach by separating adrenergic and non-adrenergic pathways. α1-blockers specifically target adrenergic-mediated smooth muscle contraction, while the novel compound targets non-adrenergic pathways (including endothelin-1 and other mediators). This segmentation allows each agent to address its specific pathway without interference, achieving comprehensive coverage of all smooth muscle contraction mechanisms in BPH.
Solution Approach 2:
The invention merges two distinct treatment mechanisms into a unified therapeutic regimen. By combining α1-blockers (for adrenergic pathway inhibition) with the novel compound (for non-adrenergic pathway inhibition), the treatment addresses both major contributors to prostate smooth muscle tone. This merging creates a synergistic effect where the combined therapy achieves greater than 50% symptom improvement, overcoming the limitations of monotherapy.
2Reliability
If 5α-reductase inhibitors are used to stop prostate growth, then prostate size reduction is achieved, but the risk of symptomatic progression is reduced not more than 35-40% by monotherapy
Solution Approach 1:
The invention segments the pathogenic processes of BPH into distinct components: prostate growth (hyperplasia) and smooth muscle contraction (tone). While 5α-reductase inhibitors address the growth component, the novel compound specifically addresses the smooth muscle contraction component through non-adrenergic pathways. This segmentation allows simultaneous targeting of both pathogenic mechanisms, achieving comprehensive disease modification.
Solution Approach 2:
The novel compound developed in this invention demonstrates multi-functionality by simultaneously addressing multiple aspects of BPH pathophysiology. It inhibits non-adrenergic smooth muscle contraction (improving urinary flow and symptoms) while also inhibiting prostate stromal cell proliferation (reducing prostate growth). This multi-functional approach allows a single agent to contribute to both symptom relief and disease progression prevention, enhancing overall treatment efficacy beyond what monotherapies achieve.
3Reliability
If medical treatment is used for BPH, then symptom improvement is achieved, but discontinuation rates are high (up to 70% within 12 months)
Solution Approach 1:
The invention merges rapid symptom relief (through smooth muscle relaxation) with long-term disease modification (through anti-proliferative effects). The combination therapy provides quick improvement in urinary flow and symptoms via non-adrenergic pathway inhibition, while simultaneously reducing prostate growth to prevent future symptom recurrence. This dual action addresses both immediate and long-term needs, reducing the likelihood of treatment discontinuation.
Solution Approach 2:
The invention implements preliminary action by preventing disease progression before it occurs. The anti-proliferative effect of the novel compound acts preemptively to reduce prostate stromal cell growth, thereby preventing future enlargement and symptom recurrence. This preliminary prevention strategy, combined with immediate symptom relief, creates a comprehensive treatment that addresses both current and future disease manifestations, improving long-term treatment adherence.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The combination treatment significantly improves urinary flow by more than 30% and reduces prostate smooth muscle contractions beyond the efficacy of individual therapies, providing a more effective alternative to existing treatments.
Implementation Method 1
the highly selective polo-like kinase 1 (PLK1) inhibitor, onvansertib
Implementation Method 2
inhibiting proliferation of prostate cells
Data Source
Figure 1A~1C
Figure 2
Figure 3A~3B
AI summary
Provided is a method of treating benign prostatic hyperplasia (BPH) in a patient. Also provided is a method of inhibiting non- adrenergic contraction of a smooth muscle. Additionally provided is a method of inhibiting proliferation of human prostate cells.