Autophagy — a physiological process that involves the destruction of old or diseased cells in the body, maintaining normal functions by protein degradation — is impaired in the salivary glands of patients with Sjogren’s syndrome, but may be corrected through the use of a potential therapy called P140 peptide, according to researchers.
The study, “Rescue of autophagy and lysosome defects in salivary glands of MRL/ lpr mice by a therapeutic phosphopeptide,” was published in the Journal of Autoimmunity.
Sjogren’s syndrome is a chronic autoimmune disorder that affects the entire body. As with most autoimmune diseases, the cause of Sjogren’s is not yet fully understood, which complicates the design and development of disease-specific drugs.
In particular, it is unknown whether protein degradation is affected in patients with Sjogren’s, which is prevalent in other neurodegenerative and autoimmune diseases. Several recent studies have suggested an increase in autophagy levels in the T-cells of the salivary glands and epithelial cells in Sjogren’s patients.
Researchers set out to determine the defects that exist in the autophagy processes in Sjogren’s. They used a mouse model called the MRL/lpr mouse which spontaneously develops systemic autoimmune disease that mimics human lupus and secondary Sjogren’s syndrome. They looked at classical autophagy markers such as MAP1LC3, SQSTM1, ATG12, and LAMP2A in the salivary glands of these mice.
They were then able to identify previously unknown molecular defects of autophagy in the salivary glands of these mice. This showed there was a reduction in the number of autophagy markers when compared to healthy mice, indicating a malfunction in the autophagy process.
However, these findings contrasted with known scientific understanding about other organs in MRL/lpr mice, including the spleen, lymph nodes, and thymus. This indicates that abnormal autophagy activity is not a general feature that affects all organs or tissues of any individual with Sjogren’s syndrome.
Next, researchers showed that when the MRL/lpr mice were treated with a peptide called P140, which is known to directly affect autophagy, the various defects identified in the salivary glands were corrected, indicating its potential as a therapeutic approach.
Interestingly, a randomized Phase 2b study showed that the P140 peptide had no adverse effects and met its primary effectiveness goals in patients with lupus.
“When the autophagy processes are abnormally elevated in lymphoid organs, the P140 peptide seems to readily correct the defects,” the investigators concluded.