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Hot off the Press: PD-1 the missing link?


While there are many new studies being published at the moment relating to AI, praise be to whichever God you choose, a new study was recently published on the 4th of March, and it’s very intriguing!


A study conducted on mice, unfortunately, was recently published, focusing on a protein known as “Programmed Death 1”. This protein is produced by T and B Lymphocytes - fighter cells that make up part of the immune system. The role of this protein is to regulate how the immune cells interct with the body. It suppresses T cell inflammatory activity and downregulates the immune system’s abililty to attack the normal cells within the body. In Layman’s terms - PD-1 stops self reactive T cells from attacking the cells within the body. Therefore, it could prevent or halt autoimmune diseases - yip, that’s right folks, it may have the ability to prevent AI diseases (1).


PD-1 (blue) binding to the PD-1 ligand (4). Image Credit: molekuul_be / Shutterstock



There have been other studies showing that impaired PD-1 plays a role in AI diseases (2,3), however, this is the first study using PD-1 as a target for therapy.



PD-1 link to autoimmunity explain (5).






The study included mice models that mimicked Multiple Sclerosis and type 1 Diabetes. The researches have engineered a protein that is capable of targeting immune cells with impaired PD-1 only, all other cells with normal, well functioning PD-1 are unaffected. This protein is made up of three components; an antibody that is targeted against the impaired PD-1; cells that therefore attack the body, a toxin and a binder.


So how does it work? First, the antibody binds to the immune cells containing the impaired PD-1. This binding opens the cell up, so that the toxin can be released into the cell and then begins to destroy the cell from the inside. Lastly, the binder is attached to ensure this protein remains in the blood circulation for an extended period, allowing it to be as effective as possible. (1)


In the mice models, this protein was able to slow down the onset and progression of type 1 diabetes. The most exciting aspect of the study is that the protein not only halted disease related paralysis of MS, but after 25 days of treatment, mice that were paralyzed regained their ability to walk and the paralysis did not return (1). This is INCREDIBLE!


There are currently no regulated treatments that reverse the paralysis of MS, all treatments delay the progression of the disease but neither halt nor reverse the associated paralysis.


These kinds of studies make me extremely excited and give me great hope that a cure may be in the pipeline. It’s still very early days, this trial hasn’t even been approved for human testing yet, but we hold onto the small victories that allow a glimmer of hope!


**A side note, PD-1 has also been targeted as a vital component of cancer. As I hav previously mentioned, Cancer and AI have a few overlaps, this one included. In Cancer, the opposite is true for PD-1. Cancer cells are exceptionally smart and have the ability to convince the immune system that they are normal cells and they should therefore not be attacked. They have the ability to upregulate the PD-1 pathway to ensure the T cells do not attack (2). New studies are focusing on blocking the PD-1 pathway to ensure that the abnormal cancer cells are recognised by the immune system as dangerous and can therefore be attacked by the T cells (2,3). I find the relationship between AI and Cancer fascinating.


May this give you the same glimmer of hope it has given me.


Have the most amazing week!


Sending love,


Cayla



References:

1. Zhao, Peng, et al. “Depletion of PD-1-Positive Cells Ameliorates Autoimmune Disease.” Nature Biomedical Engineering, 4 Mar. 2019, doi:10.1038/s41551-019-0360-0.


2. Zhou, Jing, et al. “Endogenous Programmed Death Ligand-1 Restrains the Development and Onset of Sjӧgren’s Syndrome in Non-Obese Diabetic Mice.” Scientific Reports, vol. 6, no. 1, 14 Dec. 2016, doi:10.1038/srep39105.


3. Sharpe, Arlene H, et al. “The Function of Programmed Cell Death 1 and Its Ligands in Regulating Autoimmunity and Infection.” Nature Immunology, vol. 8, no. 3, 15 Feb. 2007, pp. 239–245., doi:10.1038/ni1443.


4. Wilson, Damien. "Programmed Cell Death Protein 1 (PD1) and Cancer." News Medical , lifesciences. Accessed 18/03/2019.


5. Jiang, T. T., Martinov, T., Xin, L., Kinder, J. M., Spanier, J. A., Fife, B. T., & Way, S. S. (2016). Programmed Death-1 Culls Peripheral Accumulation of High-Affinity Autoreactive CD4 T Cells to Protect against Autoimmunity. Cell Reports, 17(7), 1783–1794. http://doi.org/10.1016/j.celrep.2016.10.042

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