The route to
discovery of the first biomarker being developed by Scout Diagnostics
involves ingenuity, tenacity and most of all… serendipity. In 2003 Dr. Bert Lynn attended a conference
that reported on unusually processed peptides as a diagnostic tool for certain
cancers. This spurred the idea with Dr.
Lynn, that perhaps similar peptides existed in Cerebrospinal Fluid (CSF) that could be indicators of
neurological disorders such as Alzheimer’s Disease (AD). Upon his return to his laboratory at the University
of Kentucky, Dr. Lynn proposed a research project to Dr. Mark Lovell to
evaluate aberrant peptides present in CSF as potential biomarkers of AD With Dr. Lovell’s experience in neurological
diseases, and Dr. Lynn’s expertise in mass spectrometry, the team possessed the
skills and tools necessary to begin the search for novel peptides that
could be indicators of AD
As with many research projects, the results were not what
they suspected. The peptides that they
had hoped would be there as indicators of AD were elusive. In an attempt to provide order to chaos, the
team segregated the existing proteins of CSF
by mass into 0-50 kd
50-100 kd and 100 kd and above
fractions. When they separated the CSF
into these fractions, they began to see a pattern. They started seeing small proteins in the 50
to 100 kd fraction, that should not be there.
This triggered the team to consider looking at these proteins as a
complex. Since the proteins complexed
together, they had a mass greater than the 50 kd, but could disassociate into
individual proteins when mixed with strong denaturing buffers. These were proteins that were known
individually, but traditional thought was that they should not have interactions with each other.
The interactions of these molecules intrigued the research
team and inspired Dr. Lovell to develop an ELISA assay for one of the complexes. Little did Dr. Lovell realize that he was
developing a prototype assay that could have a far reaching impact on the state
of Alzheimer’s diagnostics. When Dr.
Lovell tested the aberrant protein complex against samples of CSF, he found a
surprisingly high correlation between the presence of the complex in AD samples
but not age-matched normal control samples or samples from subjects with other
neurological disorders. In addition, the
complex was also present in subjects with mild cognitive impairment, the
earliest clinical manifestation of AD.
Being the consummate skeptical scientist, he assumed there was a mistake
somewhere. But nonetheless, he sent the
results to Dr. Lynn as a birthday present.
Subsequent measurement of levels of the aberrant protein complex in
lumbar CSF from living probable AD and age-matched normal control subjects in
double blind study has shown that the complex accurately identified 28 of 29
subjects tested (93% specificity). The
commercial development of this exciting invention continues and the Scout
Diagnostic’s team is hopeful that they will be able to provide a meaningful
tool for the early diagnosis of Alzheimer’s Disease.