MAY 23, 2017 10:57 AM PDT

New Approach to Treating Autoimmune Disease: "PPCA"

WRITTEN BY: Kara Marker

To treat autoimmune diseases like multiple sclerosis (MS) and hemophagocytic lymphohistiocytosis (HLH), it’s important to sacrifice as few healthy immune cells as possible. While the autoimmune reaction is indeed damaging to the body, the immune system is still needed for protection against regular exposure to agents like viruses and bacteria. A new approach seems to find the right balance, from scientists at Cincinnati Children's Hospital Medical Center.

Activated mouse T-cells with markers indicating DNA damage repair signaling (shown in pink). Credit: Cincinnati Children's

In mouse models of both MS and HLH, researchers saw that genomic stress results in DNA damage in rapidly expanding T cells. "Because T cells are always in a race with different viruses and bacteria, they have learned how to adapt and divide rapidly to respond, but this stress on their DNA means they also are living right on the edge of death," described lead author Michael B. Jordan, MD.

Jordan’s study involved inhibiting the normal process of DNA damage repair in MS and HLH mouse model cells. They used nutlin molecules to alter p53 activity, a protein responsible for regulating DNA damage repair. Additionally, CHK1/2 and WEE1 cell cycle checkpoint proteins were inhibited. “We threw them off balance and into a chasm of death,” Jordan explained

After manipulating the cells to inhibit DNA repair, researchers applied their new treatment approach, “p53 potentiation with checkpoint abrogation,” or PPCA. Abrogation describes a method of treating cancer where cell cycle checkpoints are inhibited.

In HLH mouse models, researchers saw PPCA reducing disease and improving long-term survival. In mouse models of MS, the treatment eliminated “aggressively expanding” T cells and “either reversed or prevented paralysis. While the present findings are promising, the study researchers stress that much research still needed to illustrate how PPCA could one day be applied to human cases of immune diseases like MS and HLH.

About MS

MS is characterized by an autoimmune attack on the central nervous system, specifically the protective layer of myelin sheath that coats and insulates nerves. Because of this attack, MS results in muscle weakness, numbness, or loss of coordination.

About HLH

HLH is a disease caused by too many activated immune cells, either an acquired condition through viral or bacterial infections or an inherited condition through genetic mutations.

HLH can cause a variety of symptoms, including fever, enlarged liver or spleen, cytopenia, and neurological abnormalities. Treatment options vary depending on the source of disease: antibiotics and antivirals are used to treat the infections that triggered HLH and allogeneic hematopoietic cell transplantation, chemotherapy, and immunotherapy are options to replace or destroy excess immune cells in cases of inherited HLH.

The present study was published in the journal PNAS Early Edition.

Sources: PubMed Health, National Center for Advancing Translational Sciences, Cincinnati Children's Hospital Medical Center

About the Author
  • I am a scientific journalist and enthusiast, especially in the realm of biomedicine. I am passionate about conveying the truth in scientific phenomena and subsequently improving health and public awareness. Sometimes scientific research needs a translator to effectively communicate the scientific jargon present in significant findings. I plan to be that translating communicator, and I hope to decrease the spread of misrepresented scientific phenomena! Check out my science blog: ScienceKara.com.
You May Also Like
JUL 19, 2018
Microbiology
JUL 19, 2018
Mom's Microbiome has a Big Impact on Kid's Autism Risk
For many years, scientists have been trying to learn more about the causes of autism....
SEP 14, 2018
Immunology
SEP 14, 2018
Zika Strong Arms the Immune System
Zika Virus manipulates the genetic makeup of immune cells called macrophages....
SEP 25, 2018
Immunology
SEP 25, 2018
A Better Place to Gain Weight
Weight gain among genders can have different outcomes....
OCT 10, 2018
Microbiology
OCT 10, 2018
It's Time for Your Annual Flu Shot
After last year's flu season killed around 80,000 people, the CDC is trying to get the word out about the flu vaccine....
OCT 14, 2018
Immunology
OCT 14, 2018
Malaria Vesicles Activating Immune Responses
Red blood cells infected with malaria will secrete small vesicles that activate pathogen receptors...
NOV 13, 2018
Immunology
NOV 13, 2018
Yin & Yang: The Duality of Cancer-Associated Fibroblasts in Pancreatic Cancer
Pancreatic Cancer is a devastating disease. Fifty-five thousand new patients were diagnosed this year in the United States (1). It is painful and usua...
Loading Comments...