A New Era in Medicine: The Therapeutic Promise of HMO-Based Medications

April 13, 2023 - Human breast milk has long been recognized as the optimal source of infant nutrition, providing essential nutrients and antibodies that promote growth and protect against infection. However, research has revealed that breast milk contains much more than nutrients and antibodies — it also comprises a complex mixture of sugars known as human milk oligosaccharides (HMOs) that show promise as a new class of drug developed to treat gut–brain axis (GBA) disorders.

What Are Human Milk Oligosaccharides?

Human milk oligosaccharides are complex carbohydrates found in breast milk and play a crucial role in shaping infants’ microbiome, immune system, and overall health. After lactose and lipids, HMOs are breast milk's third most abundant component. However, unlike lactose and lipids, HMOs are indigestible by infants and instead serve as a source of nutrition for the beneficial bacteria that colonize the gut.

In addition to promoting the growth of beneficial bacteria, HMOs have been found to have a range of other health benefits, including reducing the risk of infections and allergies. Most recently, scientists have begun to explore the potential of HMOs as a new class of medications for a range of gut–brain axis disorders, explained Alex Martinez, JD, CEO and Co-Founder of Intrinsic Medicine, in an interview with PharmaNewsIntelligence.

These properties have captured the attention of scientists and pharmaceutical researchers, leading to investigations into the potential therapeutic applications of HMOs.

“One of the unique things about human milk biology is that — in a way — human milk is the original oral human drug,” emphasized Martinez.

HMO-Based Drugs

By promoting the growth of beneficial bacteria in the gut, regulating immune function, and reducing inflammation, HMO-based drugs have the potential to serve as new medications for the treatment of GBA disorders, encompassing a range of conditions such as irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and neurodevelopmental disorders.

These conditions affect millions worldwide, and existing treatment options often come with limitations regarding safety and tolerability, leaving many patients without adequate relief, said Martinez. By leveraging human milk biology, Martinez and his organization aim to reproduce the beneficial effects of natural HMOs by creating synthetic biology-manufactured HMOs.

“Because it would be unfeasible to derive HMOs from humans at any ethical scale, these compounds are produced using synthetic biology. Still, they have an essentially human identical structure,” Martinez continued. “Non-human mammals have typically less diversity and lower concentrations of HMOs, which makes these compounds in human beings very special.”

These drug candidates are designed to modulate the immune system and other human cells directly, potentially affecting multiple pathways implicated in GBA disorders while reproducing the favorable safety and tolerability profile observed in natural HMOs.

“The use of HMO-based compounds as a potential therapeutic strategy for rare diseases, gut microbiome modulation, and immuno-oncology is a promising area of research,” shared Martinez. “If successful, HMO-based drugs could offer safer and more effective treatment options for patients with GBA disorders who currently have limited choices.”

Benefits of HMO-Based Drugs

Human milk oligosaccharides-based drugs hold significant potential to transform the treatment regimen for GBA disorders and other inflammatory conditions. These drugs have the potential to offer new hope to patients through their unique mode of action, favorable safety profile, and ability to address unmet needs in large, underserved populations.

“Safety is the guiding principle,” reassured Martinez. “These pro-homeostatic compounds are stable inside and outside the body and are stored in powder form for a better product profile.”

In the interview, Martinez revealed that the powder form of HMO-based drugs has a shelf-life stability of 5 years at room temperature. Powdered drugs with extended shelf lives offer several benefits, including greater storage flexibility, cost-effectiveness through bulk production and distribution, ease of dispensing and administration, and increased access to medication in remote or resource-constrained areas where restocking or refrigeration may be challenging.

Additionally, the use of synthetic biology for manufacturing HMOs offers scalability and consistency, which may increase accessibility to these therapies for patients in need. With this innovative approach, HMO-based therapeutics could reinvent the standard of care and improve patients’ quality of life.

Drawbacks of HMO-Based Drugs

Despite the promise of HMOs as a new class of medications, there are a few challenges to their development and use. For example, HMOs are complex molecules that are difficult and expensive to produce. In addition, these compounds have a short half-life in the body, meaning they may need to be administered frequently or in high doses to achieve therapeutic effects.

“There is an apparent optimal dose for these compounds — infant studies have shown that the best results are obtained within an optimal dosing range,” highlighted Martinez. "While there are no safety concerns associated with exceeding dosage, it may result in a decrease in efficacy.”

According to Martinez, despite their limitations, HMOs could transform the standard of care for GBA conditions, bringing about a paradigm shift in treatment approaches. However, further clinical development and regulatory approval processes will be crucial in determining the success of these innovative therapies.

Impacts of HMO-Based Drugs

As studies and Martinez have suggested, HMOs can promote the growth of beneficial bacteria in the gut, which can help to alleviate the symptoms of IBS. In addition, HMOs have been found to stimulate intestinal motility, which can help to regulate bowel movements and reduce the risk of constipation.

For diarrhea, HMOs have been found to have antimicrobial properties and can help to prevent the growth of harmful bacteria in the gut. Still, the potential of HMOs extends beyond gastrointestinal disorders. Research has shown that HMOs may also have therapeutic potential for various other health conditions, including neurological disorders, such as autism and schizophrenia, and respiratory infections, such as pneumonia.

With a focus on addressing the unmet needs of patients with GBA disorders and other inflammatory conditions, Martinez and his organization are dedicated to advancing HMO-based drug candidates through clinical development and regulatory approval processes. If successful, these HMO-based drugs could redefine the standard of care for these conditions and bring new hope to millions of patients worldwide.

“Although the primary understanding of HMO compounds has been focused on infant nutrition, the oligosaccharide approach has emerged as the leading and most likely way to modulate the human gut microbiome appropriately," Martinez concluded.