Non-invasive Assessment of Therapeutic Toxicity and Efficacy from Physiologic Measurements (BIDMC 895)

Category:    Diagnostics/Biomarkers

KeyWords:  Screeing Method;  Educational Tool;  Method;  

BIDMC ID:    895

Abstract:

Background: A fundamental problem in the development of novel therapeutic agents and the ongoing monitoring of approved therapeutic drugs is the sensitive assessment of their safety and efficacy. Current methods for evaluating both efficacy and toxicity largely fail to account for the effects of therapeutic drugs on integrative physiologic functions. Therefore, there is a great need to develop systems-based technologies that can provide a more efficient and cost-effective method for evaluating the safety and efficacy of drugs and other therapeutic intervention. Invention: Investigators at Beth Israel developed a novel approach that provides a way to assess the safety and efficacy of drugs by measuring their effects on integrative physiologic function. This approach is based on the discovery that pathologic and other maladaptive states are characterized by loss of complex information, for example, less complex variation between heartbeat intervals. And vice versa, more complex information (enhanced complexity), for example, more complex variability in heartbeat intervals, is consistent with a healthy state. Examined drugs or therapeutic interventions that enhance system complexity are likely to be associated with positive therapeutic effects, whereas interventions that degrade system complexity are likely to be associated with adverse effects that may escape detection by conventional assessments.

Inventor:   Ary L. Goldberger, MD Chung-Kang Peng, PhD Madalena Costa, MS

Commercial Opportunity:

 To enable the assessment of therapeutic efficacy and toxicity in preclinical animal studies and Phase I, II and III clinical design for the development and testing of pharmacologic agents.  To use for the testing of drugs and non-pharmacologic interventions and to screen for new therapeutic compounds with positive integrative physiologic effects that might not be detected by conventional screening.  To enable the assessment of already approved therapeutic drugs and other non-pharmacologic interventions by detecting potential toxicities not already identified in animal and Phase 1-3 trials by the FDA or other governmental agencies.

Competitive Advantages:

Current screening tests and assays for the efficacy and toxicity of pharmacologic and non-pharmacologic interventions are based primarily on local effects and on the measurement of a limited range of markers. Such measures generally fail to account for systemic effects associated with integrative feedback (“systems biology”). Thus, a drug might appear to have beneficial effects in the short-term, or based on site-specific actions. However, more sustained use might be associated with lethal toxicities not detected in the conventional evaluation. This new approach provides a systematic way of measuring the effects of pharmacologic and non-pharmacologic therapies and related interventions on integrated, multiscale system function, thereby providing a potential means of assessing efficacy and providing an early warning about potential toxicity that would likely not be otherwise detectable by conventional assays.

Related Publications:

1.      Costa M, Goldberger AL, Peng CK.  Multiscale entropy analysis of complex physiologic time series.  Phys Rev Lett 2002;89:068102-1-4.

2.      Costa M, Peng CK, Goldberger AL, Hausdorff JM.  Multi-scale entropy analysis of human gait dynamics.  Physica A 2003;330:53-60.
 
3.      Costa M, Goldberger AL, Peng CK.  Multiscale entropy analysis of biological signals.  Phys Rev E 2005;71:021906.  

State of Development:

Related Technology URL:

http://research.bidmc.harvard.edu/research/ResearchPIInfo.ASP?Submit=Display&PersonID=238

Patent Status:

Provisional patent filed by Beth Israel Deaconess Medical Centers Feb. 2005

TVO Contact Info:
     Catherine M Lenich
     Senior Associate TVO
     clenich@bidmc.harvard.edu
     Phone: 617-667-0568   Fax: 617-667-0646

     Beth Israel Deaconess Medical Center
     Technology Ventures Office  Room: BR-0200
     330 Brookline Avenue
     Boston, MA 02215