Our mission is developing new chemicals for neurodegenerative disease treatment. Our goal is to target the innate inflammatory immune system and we are in step with those people that think the body can heal itself. The theory is that pathogenesis is the creation of damage and salugenesis is the process of the body repairing the damage. Salugenesis is the automatic, evolutionarily conserved sequence of molecular, cellular, organ system and behavioral changes that are used to heal the body. Interestingly, it starts with the mitochondria and the cell. The cell danger response is interictally involved with salugenesis. We think healing dysfunctional mitochondria may be the first step in salugenesis.
What is salugenesis? As soon as an animal gets sick it begins to heal. The phases of the healing cycle are inflammation followed by proliferation and finally differentiation. Inflammation is pro-inflammatory and supports hemostasis, containment, and innate immunity. This is the part of the disease cycle involving infections…and the inflammatory part of PNE and EPM. In the next phase, adaptive immunity and regeneration play a big role. If things go well in the final anti-inflammatory stage disease resolves by remodeling and then recovery.
The key factor in the healing cycle are mitochondria. When mitochondria are dysfunctional chronic disease ensues. Any abnormal persistence of the cell danger response inhibits the healing cycle, creates dysfunction and causes the symptoms of chronic disease. Some medications allow the cell danger response to persist. Our work focuses on chronic disease and moving an animal toward healing by resetting the innate responses initiated by disease.
Some synthetic molecules when given to animals form metabolites due to hydroxylation of specific positions on phenyl rings that are detrimental. The unstable form of some drugs promote chronic disease by promoting inflammation, they are pro-inflammatory. Our intent is to generate more metabolically stable analogs of drugs that are designed to reset innate responses that wont elicit pro-inflammatory responses. Our work ensures drugs are biologically active when given, especially when given orally. The chemical analogs we created were tested in the laboratory for their effects on several parasites including C. elegans and S. neurona. Drugs not only affect the host but also have actions on the parasites, it is good to test and understand the responses in host and on the parasite. Our recent work produced 85 novel molecules to enter our drug pipeline.
Ten analogs were selected from initial screening of the 85 new drugs and then the top ten were tested for their cytokine response profile for six important disease-associated cytokines. These cytokines are important in EPM and PNE as well as some human chronic diseases. It wasn’t a surprise to find out low doses of some molecules are anti-inflammatory (stimulate anti-inflammatory cytokines) while higher doses stimulate pro-inflammatory cytokines. This property is common to regulatory molecules. We used the parent structure to compare the reactions and effects of the novel drugs in vitro and that gives us an idea how we can change the outcome of chronic disease. The results show that a variety of the new derivatives display useful cytokine profiles and that multiple compounds have comparable and superior metabolic stability to the parent structure.
In another set of synthesis experiments we created a molecule that may help people. It was the best molecule to reverse abnormal mitochondrial function in vitro. In addition to restoring mitochondrial homeostasis we postulate that it will decrease chronic inflammation in several diseases. The new drug may be helpful with Covid19 infections. We will know shortly if the AI predicted inhibition of a Covid 19 host cell invasion protein is true. There are other viruses that may be inhibited by our treatment and we will explore those at some future date. It is anticipated that our new molecule will treat several conditions including chronic renal disease (the application may be in people, dogs and cats) and possibly sepsis (we are thinking foals that are born septic) or even organ transplant recipients (people).
As we work our way through the experimental and regulatory processes we will keep everyone updated. We may reach out for help so stay tuned. It may be that to fast track our new drug renal disease would be the best target, if that is the path we choose we will be seeking old dogs with end stage renal disease. You can contact us early next year to sign up for that program. We will get with FDA in January and see what they think. As we blaze new trails we will seek special designations that can get our treatment to those that need it.