Home Health Explaining The Validation Process of Meso Scale Discovery (MSD) Assay

Explaining The Validation Process of Meso Scale Discovery (MSD) Assay

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The validation process of meso scale discovery (MSD) can be looked at in two phases; the first, focusing on the development of the assay, and the second on modifying it to suit your needs.

There are several steps involved in getting an initial MSD assay validated. These include identifying critical parameters, including PK or PD endpoints, selecting surrogate markers for these endpoints where possible.

In addition, defining sample collection criteria and sample handling procedures for both study subjects and controls, deciding how you want to analyze your data [e.g., by pharmacodynamic (PD) measures like a change from baseline], choosing critical dose-ranging studies with appropriate clinical measurements as well as healthy volunteer studies to assess side effects or organ function, etc.

The Validation Process of The Meso Scale Discovery (MSD) Array

1. Critical Parameters

As stated above, it is essential to identify the critical parameters of interest for the assay. These may include PK parameters, PD parameters, or both. For example, if you are interested in determining whether a new drug can extend life span in mice, then the critical parameter would be an increase in mean survival time or maximum life span. This could be replicated using a process similar to the screen-to-hit (S2H) strategy for drug discovery. In this case, PK endpoints are not as helpful because they are not actionable for SAR development. PD endpoints, on the other hand, are very useful for novel drug screening. If you are interested in determining which genes can extend lifespan in mice, the critical parameters would be telomere length, mitochondrial DNA (mtDNA) copy number, or micro-RNA (miRNA) transcripts.

2. Identifying Surrogate Markers for Critical Parameters of Interest

This is probably the most crucial step in determining whether an MSD assay can be validated at all. The two primary goals of any MSD mesoscale are toxicity and efficacy. Altering one of these criteria will almost certainly influence both toxicity and effectiveness, resulting in a poor validation rate or inability to detect minor effects on either endpoint with acceptable specificity. Surrogate markers are critical for this reason because they provide a link between your two endpoints. For example, suppose a candidate compound alters a surrogate marker to predict a change in a vital endpoint with acceptable specificity. In that case, the candidate compound can likely alter the critical endpoint as well.

3. Identification of the Whole Process Before Execution

To identify appropriate surrogate markers for your desired endpoint, you must first know what you are trying to measure with the assay. In most cases, this means identifying gene products or protein expression patterns associated with the desired endpoint for MSD immunogenicity assay. You can use various tools to accomplish this, including gene expression chips, microarrays, ChIP- ChIP, and proteomics. Moreover, many vendors will also offer custom annotation of your array using curation software such as Ingenuity Pathway Analysis (Ingenuity Systems).

Conclusion

Once you have a list of genes or proteins that co-express with the endpoint you want to measure, you need to know what makes an excellent surrogate marker. The first step is to identify which gene products are more likely to be altered by your desired endpoint than those of other genes not affected by it. You can use Ingenuity Pathway Analysis for this task as well. For the validation process to be successful, these are the  necessary steps.