MMP-14 Levels May Serve as Biomarker and Therapeutic Target in FAP Patients

MMP-14 Levels May Serve as Biomarker and Therapeutic Target in FAP Patients
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Matrix metalloprotease-14 (MMP-14) is a novel biomarker for therapy follow-up, as well as a potential therapeutic target in familial amyloidotic polyneuropathy (FAP), said researchers in Portugal.

Their study, “MMP-14 overexpression correlates with the neurodegenerative process in familial amyloidotic polyneuropathy,” appeared in the journal Disease Models and Mechanisms.

FAP is characterized by the misfolding and deposition of a mutant protein called transthyretin (TTR) into nerves of the peripheral nervous system (PNS).

MMPs are a group of proteins that are expressed in response to either an injury or a neurological disease. Levels of one particular MMP, called MMP-14, are elevated in Alzheimer’s and other neurodegenerative and neuroinflammatory diseases in studies that looked at both mouse models and human biopsies.

In fact, higher levels of MMP-14 correlated with regions of deposits of mutant protein aggregates in Alzheimer’s disease models.

Researchers set out to determine the expression levels of MMP-14 in FAP mouse models and tissue samples from FAP patients that have the TTR V30M mutation — the most common mutation associated with FAP — in order to determine whether MMP-14 could be used a biomarker for neurodegeneration.

The results showed that MMP-14 is indeed overexpressed in human FAP-affected nerves, and levels were correlated with mutant TTR swpoaira. Researchers further proved this link by showing that MMP-14 is increased in the sciatic nerves of mouse model of FAP. Levels of MMP-14 rose with increasing amounts of TTR deposits.

Then, researchers showed that levels of MMP-14 in the peripheral nervous system decreased when treated with an anti-inflammatory drug or by reducing TTR production, indicating that the inflammatory response and TTR are involved in increasing levels of MMP-14.

Moreover, MMP-14 levels were increased in Schwann cells — a type of nerve cells affected in FAP — when the cells were incubated with protein aggregates. This result showed a direct relationship between the presence of protein aggregates and an increase in MMP-14 levels.

Finally, researchers showed that MMP-14 in the plasma of FAP patients increases as the disease progresses.

While the exact role of MMP-14 is unclear, the authors write, “the demonstration of increased MMP-14 in the periphery, together with its augmented levels in plasma from FAP patients, especially in advanced stages of disease, denote a correlation between this MMP and neurodegeneration, highlighting its potential role as a novel disease biomarker or even as a promising future therapeutic target.”

Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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Iqra holds a MSc in Cellular and Molecular Medicine from the University of Ottawa in Ottawa, Canada. She also holds a BSc in Life Sciences from Queen’s University in Kingston, Canada. Currently, she is completing a PhD in Laboratory Medicine and Pathobiology from the University of Toronto in Toronto, Canada. Her research has ranged from across various disease areas including Alzheimer’s disease, myelodysplastic syndrome, bleeding disorders and rare pediatric brain tumors.
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