INTiDYN has developed solutions for customers spanning academic institutions, pharmaceutical and biotechnology companies, and other medical professions. The case studies below highlight just a few of the ways INTiDYN has applied CMA 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 (ie, 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 assignment

Our client developed a novel therapeutic that they hypothesized would prevent or reverse this type of pathology. INTiDYN was asked to determine if this hypothesis was accurate.

Result

ITD-CMA indeed confirmed that the therapeutic was successfully impacting the predicted innervation. However, the detailed analysis also discovered something else.

Value of INTIDYN interpretation

  • The comprehensive data generated by CMA detected 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 assignment

INTiDYN was asked to determine if the client’s therapeutic agent was limiting chemotherapeutic damage to cutaneous innervation.

Result

Using different immunochemical markers than 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 of the standard neuronal biomarkers. The innervation was mostly still present.

Value of INTIDYN interpretation

This finding dramatically shifted the therapeutic strategy from attempts to prevent neuronal loss to those that would act to 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 chronic pain may be due to an increase of spontaneous activity among neurons in the spinal cord due to a loss of sensory input (ie, deafferentation syndrome)

INTiDYN assignment

The client was performing a human study that evaluated physiological assessments of sensory nerve function (microneurography) to lay the groundwork for future therapeutic strategies to treat neuropathic pain by promoting regeneration of cutaneous innervation. INTiDYN was asked to perform CMA of cutaneous innervation to assess a wide variety of neuropathic conditions.

Result

CMA revealed that a comparable loss of intraepidermal nerve fibers also occurred in neuropathies that were not painful, indicating that additional mechanisms beyond innervation loss were likely involved.

Value of INTIDYN interpretation

  • These results demonstrated that a loss of epidermal nerve fibers was not necessarily the cause of chronic pain
  • The comprehensive evaluations discovered previously unknown changes in other biomarkers among skin compartments that more consistently correlated with the presence of neuropathic pain, particularly among epidermal keratinocytes
Icon

30+ years of published expertise

The scientific founders of INTiDYN, Dr. Frank L. Rice and Dr. Phillip J. Albrecht, are the foremost established experts in a holistic, comprehensive research approach that is renowned for integrating high-resolution, multi-molecular morphological assessments across a wide range of nonhuman and human research models.

See the impact of our research