Exploring Treatment Options for IPEX Patients with Gut Microbiome Insufficiencies
A recent study reveals a key connection between gut bacteria and a rare autoimmune disease that can provide a basis for more effective treatment. Image Credit: Flickr user AJC1
A recent research breakthrough at the University of Texas Health Science Center at Houston McGovern Medical School bodes well for patients with immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) Syndrome, a rare autoimmune disease that can be fatal. The disease is characterized by a genetic mutation that leads to a deficiency in regulatory T cells (T reg cells), causing inflammatory conditions like eczema, type I diabetes and enteropathy.
What the University of Texas scientists realized was that the genetic mutation was also associated with a decrease in the levels of Lactobacillus reuteri in the gut microbiome. Under normal circumstances, L. reuteri produces inosine, a metabolite that binds to adenosine A2A receptors to prevent the production of pro-inflammatory T-cells. Without this inhibitor, inflammatory processes in IPEX patients go unchecked, which explains the symptoms they experience. Based on their findings, the researchers proposed several possible IPEX treatment options that will ease patients’ symptoms and restore them to a higher standard of living.1 Using modern software, researchers at life sciences can explore these options and identify the best one to bring to market.
Researching Different Treatment Options for IPEX Syndrome
When the researchers conducted studies in mice, they found that replacing inosine could reduce inflammatory processes and significantly extend lifespan.2 This led them to propose several possible ways that IPEX syndrome could be treated in human patients:
- Directly replacing inosine
Perhaps the simplest way to treat IPEX that the researchers discovered was to provide them with inosine as a small molecule drug. In order to find out if this option will work well enough to make it into clinical trials and ultimately store shelves, scientists will need to conduct extensive tests to determine the safety and efficacy of a proposed drug, as well as explore possible delivery methods to find the one that is the most effective. With the predictive analytics capabilities of modern software, scientists may be able to get an idea whether a particular inosine formulation or delivery method will be effective, before they start running physical tests in the laboratory. This can help reduce the overall failure rates for inosine formulations during animal and clinical trials, saving the lab time and money.
- Treating patients with a different A2A receptor agonist
A closely related treatment possibility for IPEX patients would be to provide a different A2A receptor agonist in place of inosine, which could act as a similar or even more potent immune suppressor. Because modern software makes it easier to process large amounts of data, scientists can quickly sort through a wide range of A2A agonist candidates and quickly dismiss those that are likely to fail. Once the pool of possible small molecule drugs has been narrowed down, scientists can run similar predictive tests as they did for inosine in order to determine whether it makes sense to bring a small molecule drug to the bench, run animal tests and prepare for clinical trials.
- Providing patients with a probiotic supplement
The third, somewhat less conventional option would be to replace inosine in IPEX patients by having them take a probiotic supplement containing L. reuteri. That way, the healthy state of the microbiome could be restored despite the genetic mutation. However, it may be tricky to determine the probiotic dosage necessary to get the right balance of bacteria in the gut—the treatment needs to be effective without disrupting other microbiome-related processes. Advanced data analytics technology can make it easier to conduct and interpret predictive tests and physical experiments that reveal the effects of different dosages and formulations on the state of the gut microbiome.
Reducing the Time to Market for an IPEX Treatment
Currently, the only treatment option for individuals born with IPEX syndrome is a stem cell transplant, but finding a suitable donor match can be difficult. As a result, many patients die before reaching the age of two years,3 so getting a new drug on the market could make a huge difference in the lives of the families affected by the disease. By improving drug candidate selection and thereby cutting down on the number of candidates that fail in the later stages of clinical trials, modern software solutions can help decrease the time it takes to get an effective drug into the hands of the patients who need it.
At the same time, cutting down on the R&D time reduces the overhead costs associated with the development of a new drug for a rare disease. Since this factors significantly into the final drug cost, utilizing modern software can make high-quality treatments more affordable for patients and families. It also makes it more financially feasible for life science companies to invest valuable time and resources into pursuing solutions for rare diseases like IPEX.
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- “Gut Bacteria May Hold Key to Treating Autoimmune Disease,” December 15, 2016, http://www.newswise.com/articles/gut-bacteria-may-hold-key-to-treating-autoimmune-disease ↩
- “Resetting microbiota by Lactobacillus reuteri inhibits T reg deficiency-induced autoimmunity via adenosine A2A receptors,” December 19, 2016, http://jem.rupress.org/content/214/1/107 ↩
- “Gut bacteria may hold key to treating autoimmune disease,” December 19, 2016, https://www.sciencedaily.com/releases/2016/12/161219100126.htm ↩