Microbiome Therapies and Repurposed Drugs for NASH and NAFLD Treatment

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• Microbiome Therapy for NASH and NAFLD
• Lean NASH and Microbiome Connection
• Natural Supplements for NASH Treatment
• Drug Repurposing for NASH Therapy
• Commercial Barriers in NASH Research
• Full Transcript

Microbiome Therapy for NASH and NAFLD

Dr. Scott Friedman, MD, describes innovative microbiome-based strategies for treating non-alcoholic fatty liver disease. The approach involves transplanting healthier bacteria profiles into patients. This method effectively uses "bugs as drugs" to combat NASH progression.

Dr. Scott Friedman, MD, explains that manipulating the endogenous microbiome shows promise. This can be achieved through probiotics or selective antibiotics. These interventions aim to transform the gut environment and improve liver health.

Lean NASH and Microbiome Connection

Dr. Scott Friedman, MD, highlights a compelling link between microbiome abnormalities and Lean NASH. Patients with Lean NASH have normal body weight but still develop fatty liver disease. This suggests non-traditional drivers are at work in these cases.

According to Dr. Friedman, genetic factors and ethnic risks also contribute to Lean NASH. The unusual microbiome composition in these patients may trigger NAFLD development. This insight opens new avenues for targeted microbiome therapies in specific patient subgroups.

Natural Supplements for NASH Treatment

Dr. Anton Titov, MD inquires about natural compounds like butyrate and curcumin for NASH treatment. These substances show potential for reducing pro-inflammatory cytokines including NF kappa B. They represent accessible over-the-counter options for patients.

Dr. Scott Friedman, MD, acknowledges these natural compounds might be effective. However, he notes pharmaceutical companies show little interest in developing them. The lack of patent protection makes them commercially unattractive despite potential benefits.

Drug Repurposing for NASH Therapy

Dr. Scott Friedman, MD, discusses the promising approach of drug repurposing for NASH treatment. Existing medications developed for other conditions might show efficacy against fatty liver disease. This strategy leverages known safety profiles of established drugs.

Dr. Friedman's laboratory has conducted studies showing surprising benefits of repurposed drugs in NASH. These findings suggest multiple existing medications could be effective liver therapies. The challenge lies in moving these discoveries from laboratory to clinical application.

Commercial Barriers in NASH Research

Dr. Scott Friedman, MD, identifies significant commercial barriers in NASH drug development. Pharmaceutical companies prioritize patent-protected compounds over natural supplements or generic drugs. This creates a treatment gap for potentially effective therapies.

Dr. Scott Friedman, MD, emphasizes that real-world drug development involves more than just efficacy and safety. Commercial considerations often determine which treatments receive research funding. He advocates for foundation and government support to fill this critical development gap.

Full Transcript

Dr. Scott Friedman, MD: You also mentioned in one of your reviews there are strategies: "drug the bug" and also "bugs as drugs" to treat non-alcoholic fatty liver disease and NASH. That's right. So it could be transplanting bacteria that have a more healthy profile—effectively, the bug becomes a drug.

This, along with trying to change the endogenous microbiome either by manipulating with probiotics or perhaps selective antibiotics, can ultimately transform the microbiome and hopefully change the nature of NASH.

I think the microbiome becomes particularly compelling as a driver in those patients with lean NASH. After all, they don't have excess fat in the liver and obesity, and yet they have NASH.

To me, that—along with genetic factors and ethnic risks—speaks to the idea that those NASH patients could have an unusual microbiome or unusual components of their microbiome that are leading to NAFLD, even though they are lean.

Again, it's early days, really, but I'm confident we'll continue to make progress.

Dr. Anton Titov, MD: What about strategies using small molecules or natural substances such as butyrate or curcumin to decrease pro-inflammatory cytokines, including NF kappa B?

Dr. Scott Friedman, MD: The current approach from the pharmaceutical and biotech industry is to identify drug targets either in the intestine or in the liver that can regulate and therefore lead to resolution or improvement in NASH.

Butyrate, not so much. There's a slightly cynical perspective on this: the natural compounds and chemicals that might be available to us over the counter as supplements are not of great interest to the pharmaceutical industry because they can't be patented and cannot yield commercial success.

I think we need to acknowledge that there may be treatments out there—even existing drugs that could be repurposed—but they are not being adequately pursued because there's no commercial incentive.

There's no company that's going to benefit commercially from that drug. So it becomes a little hard to test things like butyrate, in part because there's no commercial interest in developing those kinds of therapies.

That is a place where I think foundations and government agencies can fill an important gap in trying to use either natural compounds that are well-characterized and safe, or even repurposed drugs that are already off their patent life but could be very well tolerated.

We've done a couple of studies in my laboratory showing that drugs that have already been tried for other diseases, to our surprise, have a benefit in NASH as well.

Unfortunately, we've not been able to engage the commercial sponsors that hold the patents to actually repurpose those drugs and invest in a clinical NASH therapy program.

So there are some real-world considerations about how drugs are developed beyond just whether they're effective and safe. I wish it weren't so, but that's just the way the system works.