Two New Genetic Mutations 
Associated with 
Cowden Syndrome Identified

Tuesday, February 26, 2013
Specialty: 

Cleveland Clinic researchers from the Lerner Research Institute have uncovered two new genes associated with Cowden syndrome (CS) according to a new study, published on December 13, 2012, in the online version of the American Journal of Human Genetics.

Cowden syndrome is a difficult-to-recognize, under-diagnosed condition that carries high risks of breast, thyroid and other cancers. The discovery of the two new genes — led by Charis Eng, MD, PhD, Chair and Founding Director of the Cleveland Clinic’s Lerner Research Institute’s Genomic Medicine Institute — will promote diagnosis and clinical management of the disease, while also assisting in predictive genetic testing and genetic counseling.

This research comes on the heels of two new discoveries by Dr. Eng, both related to Cowden syndrome and the PTEN gene, that were recently published in the Journal of Clinical Endocrinology & Metabolism. In a November 2012 paper, Dr. Eng and her team reported on uncovered, untapped, diagnostic and prognostic pathways for cancers related to the compromised PTEN tumor suppressor. This discovery that PTEN disrupts cancer signaling pinpoints a novel target for future treatment and diagnosis.

In another paper published in December 2012, Dr. Eng and her team identified a screening biomarker in thyroid cancers that revealed inherited predisposition in Cowden syndrome patients. With the increasing incidence of thyroid cancer over the last few years, having a biomarker to screen for an inherited mutated PTEN tumor suppressor gene would accelerate follow-up for affected individuals.

After a five-year, multi-center study of patients with Cowden syndrome and Cowden-like syndrome, researchers have concluded that a simple blood test may screen for individuals carrying increased cancer risk. Until now, only four clinical factors were known to predict an inherited PTEN mutation — and this study’s blood test out-predicts them all. Future studies testing thyroid tissue itself may reveal additional biomarkers.

Potential Drug for 
Alzheimer’s Disease

A compound developed to treat neuropathic pain has shown potential as an innovative treatment for Alzheimer’s disease, according to a study by researchers at Cleveland Clinic’s Lerner Research Institute and Anesthesiology Institute.

“Cleveland Clinic dedicated two years of research into the examination of this compound and our findings show it could represent a novel therapeutic target in the treatment of Alzheimer’s disease,” says Mohamed Naguib, MD, Professor of Anesthesiology, Cleveland Clinic Lerner College of Medicine. “Development of this compound as a potential drug for Alzheimer’s would take many more years, but this is a promising finding worthy of further investigation.”

In a study published online in the Neurobiology of Aging, the compound MDA7 induced beneficial immune responses that limited the development of Alzheimer’s disease.

Treatment with the compound restored cognition, memory and synaptic plasticity — a key neurological foundation of learning and memory — in an animal model.

Neuroinflammation is an important mechanism involved in the progression of Alzheimer’s disease. The MDA7 compound has anti-inflammatory properties that act on the CB2 receptor — one of the two cannabinoid receptors in the body — but without the negative side effects normally seen with cannabinoid compounds.

Dr. Naguib is named on two patent applications on CB2 modulators submitted by the University of Texas MD Anderson 
Cancer Center.