Integrated Tissue Dynamics (INTIDYN) has applied their capabilities to create solutions for many types of customers spanning across Academic Institutions, Pharmaceutical and Biotechnology Companies and other Medical Professions. Below are three case studies highlighting some of the ways in which INTIDYN has applied their analysis and advisory services.

Case Study 1: Preclinical Detection of a Severe Side Effect
Background
  • Nerve injuries have been shown to commonly result in severe pain caused by stimuli that are not normally painful (i.e. allodynia).
  • Published studies have shown that this condition is accompanied by alterations in epidermal sensory innervation that expresses the neuropeptides CGRP and Substance P.
INTIDYN's Assignment
  • Our client developed a novel therapeutic that they hypothesized would prevent or reverse this pathology. INTIDYN was asked to determine if this hypothesis was accurate.
Result
  • ITD-CMA confirmed that the therapeutic was successfully impacting the predicted innervation.
Value-Added Interpretative Result Based on ITD-CMA:
  • However, we first unblinded the study by detecting that the therapeutic was profoundly disrupting the structural integrity of the cutaneous arterioles.
  • In this case we were able to warn our client that their promising therapeutic had a potentially serious vascular side-effect.

 

Case Study 2: Rectifying an Incorrect Hypothesis Redirects a Therapeutic Strategy
Background
  • Several studies have documented that pain and numbness caused by chemotherapy is accompanied by a loss of cutaneous innervation.
  • Our client developed a novel therapeutic that was designed to prevent the loss of cutaneous innervation caused by a standard chemotherapy regimen.
INTIDYN's Assignment
  • Determine if our client’s therapeutic agent was limiting chemotherapeutic damage to cutaneous innervation.
Result
  • Using different immunochemical markers from those routinely used to detect sensory endings, our ITD-CMA revealed that the chemotherapy was not causing a loss of innervation but was, in fact, causing a down regulation among the standard neuronal biomarkers.
Value-Added Interpretative Result Based on ITD-CMA:
  • This finding shifted the course of the study from attempts to prevent neuronal loss to strategies that would restore normal neuronal biochemistry.

 

Case Study 3: Discovering Previously Unknown Therapeutic Targets
Background
  • Many studies of humans with various types of painful peripheral neuropathies have documented a loss of intraepidermal nerve fibers.
  • This has led to a hypothesis that the chronic pain may be due to an increase of spontaneous activity among neurons in the spinal cord due to a loss of sensory input (i.e. deafferentation syndrome).
INTIDYN's Assignment
  • Our client was running a human study that combined physiological assessments of sensory nerve function (microneurography) with our ITD-CMA of cutaneous innervation to assess a wide variety of neuropathic conditions.
Result
  • The purpose of the study was to lay the groundwork for future therapeutic strategies to treat neuropathic pain by promoting regeneration of cutaneous innervation.
Value-Added Interpretative Result Based on ITD-CMA:
  • However, our results also revealed that a comparable loss of intraepidermal nerve fibers also occurred in neuropathies that were not painful.
  • These results demonstrated that a loss of epidermal nerve fibers was not necessarily the cause of chronic pain.
  • In the course of the study we did discover previously unknown changes in other biomarkers that more consistently correlated with the presence of neuropathic pain.