Biomedical Engineering Researcher Receives Grant to Study Novel Lupus Drug
July 22, 2014
Audrey Grayson

In 2012, biomedical engineering professor Chandra Mohan published a study in the journal Arthritis Research & Therapy which outlined the use of a new drug that successfully treated lupus in mice and reduced the number of cases of lupus-related kidney disease.

Mohan, who serves as Hugh Roy and Lillie Cranz Cullen Endowed Professor of biomedical engineering at the University of Houston Cullen College of Engineering, worked closely with collaborators at Pharmacyclics, Inc. – a biopharmaceutical company that designs, develops and commercializes novel medical therapies and treatments – to conduct his research on this novel drug for lupus patients. Now, Mohan has received a $250,000, two-year grant from Pharmacyclics to expand this research by studying an improved version of the same drug on mice with several other autoimmune diseases.

The drug that Mohan and his Pharmacyclics collaborators are focused on works by targeting B cells, which are key cells in the immune system that lead to the development of lupus. Lupus is an autoimmune disease that develops when a patient’s immune B cells begin producing antibodies which mistakenly attack the body’s own cells. Although why this happens remains a mystery, Mohan believes that by targeting and silencing these B cells, we may be able to stop or significantly delay the development of lupus in patients who have the disease.

And judging by the results of Mohan’s first attempt to study this drug in mouse models, there’s good reason to believe he might be on to something. “We found that this drug worked as an inhibitor to a key signaling molecule within B cells. In mouse models of lupus, we found it to be very effective – the mice had less antibodies and less kidney disease.”

But bad-behaving B cells aren’t responsible only for the development of lupus; B cells have been shown to play a role in nearly all autoimmune diseases, from rheumatoid arthritis to celiac disease. Based on the encouraging results from Mohan’s first attempt to study this drug in mice models, Mohan and his Pharmacyclics collaborators will now be expanding the research to look at whether the drug can be used as an effective treatment for many other systemic autoimmune diseases.

Most patients suffering from autoimmune diseases are treated with steroids, a class of immunosuppressive drugs which delay the development and progression of autoimmune diseases by suppressing the patient’s entire immune system. However, suppressing the entire immune system increases a patient’s risk for infections and other long-standing side effects.

In the past 50 years, only one drug has ever been approved for the treatment of lupus. The fact that the new drug Mohan is researching targets B cells selectively is a very exciting step forward for the treatment of lupus, he said. “The idea is that the more selective the drug is in targeting the causes of lupus, the fewer side effects there will be. Targeting the B cells without depleting them totally is what makes this drug so compelling,” Mohan explained.

Although this drug primarily targets B cells, that does not necessarily mean that the drug isn’t immunosuppressive. If Mohan and his collaborators find in this latest round of research that the drug is effective in mouse models of various autoimmune diseases, the next step will be for them to test how generally immunosuppressive the drug is.

The hope, Mohan said, is that even if this new drug is found to be immunosuppressive, it may carry fewer side effects than steroids and therefore could be approved as an alternative drug option for lupus patients. In a world where so few treatment options exist for lupus patients, adding a new option to the arsenal of drugs approved to treat the disease would be a major victory for lupus patients and healthcare providers alike.

However, Mohan said he remains cautiously optimistic about what the future holds for the treatment of lupus and other autoimmune diseases, explaining that his current research is “only the tip of the iceberg” in terms of introducing new, targeted therapies for the treatment of these diseases.

“One of the things that’s happening in the study of autoimmune diseases is the concerted effort to subset patients into different groups, as there are many different kinds of lupus,” Mohan said. “The idea is that if we can subset lupus patients according to the specific phenotypes they manifest or the specific molecules they possess, we can target therapeutics to that particular pathway.”

“In the next five years, there will be a much richer database of molecular information, and hopefully there will be 10, 20, even 30 different targets for therapeutics so treatments can be tailored to each patient,” he said.

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