Cyteir Therapeutics Releases Study Data Showing RAD51 Modulators Protect Diabetic Mice from Type 1 Diabetes.
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- US-based Cyteir Therapeutics, Inc. has released pre-clinical in vivo data demonstrating that therapeutic targeting of the AID/RAD51 axis in B cells may block development of type 1 diabetes, which has been published in the June issue of The Journal of Immunology, the company said.
This work was carried out in collaboration with The Jackson Laboratory (Bar Harbor, Maine), and Virginia Tech (Blacksburg, Virginia).
Kevin Mills, PhD., chief scientific officer of Cyteir is an author on the paper.
Cyteir holds an exclusive license from The Jackson Laboratory for certain intellectual property related to synthetic lethality. The title of the paper is: Genetic and Small Molecule Disruption of the AID/RAD51 Axis Similarly Protects Nonobese Diabetic Mice from Type 1 Diabetes through Expansion of Regulatory B Lymphocytes.
The company's approach leverages activation induced cytidine deaminase as both a biomarker and driver of DNA damage.
By modulating the DNA repair protein RAD51 in AID-positive cells, Cyteir seeks to induce selective self-destruction of cancer cells or specific B-cells in autoimmune diseases.
Preclinical studies to date have demonstrated Cyteir's early RAD51 modulators to be potent, selective for AID-positive cells, effective against cancer cells in vitro and in vivo, and well tolerated in preclinical animal models.
In autoimmune diseases, AID is directly implicated in disease development and progression, thus the use of a RAD51 modulator may have utility in mitigating autoimmune diseases as exemplified in the data presented in The Journal of Immunology peer reviewed scientific article.
The preclinical data presented are from a series of experiments using non-obese diabetic mice, a preclinical model of human type 1/juvenile diabetes. The study showed that treatment with a RAD51 modulator, which blocks the transport of RAD51 into the nucleus of AID+ cells, greatly reduced the incidence of T1D in these animals.
This study also found that targeting RAD51 significantly increased CD73+ B cells in the spleen pancreatic lymph nodes and pancreatic islets in treated mice.
These cells were capable of suppressing diabetogenic T cell responses thus enhancing the therapeutic effect of the RAD51 targeted compound. These results were achieved with intermittent and long term dosing which appeared well tolerated by the animals.
It is estimated by the American Diabetes Association that there are 1.25m children and adults in the US who have type 1 diabetes and have an unmet medical need for new therapies.
Overall the incidence of autoimmune disease is rapidly rising in the United States. The National Institutes of Health now estimates that more than 23m Americans suffer from autoimmune disorders.
Cyteir Therapeutics is in the discovery and development of novel therapeutics based on the biology of DNA repair and synthetic lethality for the treatment of cancer and autoimmune diseases.
Its initial approach takes advantage of the gain in function from DNA damage overload to induce selective self-destruction of cells by targeting disease-induce RAD51 transport.
Cyteir Therapeutics' lead molecules were initially discovered using its drug discovery platform using primary cells which contain tunable genetic constraints.
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|Date:||Jun 1, 2017|
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