Growth hormone patent targets more potent therapy designs

Ohio University researchers have filed a growth hormone patent tied to a molecular discovery that may help drug developers design stronger treatments for hormone-related disorders. The university said the work explains how a growth hormone therapy used for acromegaly blocks activity at the receptor level, a question that had remained unresolved for years.

The patent comes from a collaboration between Dr. John Kopchick of the Heritage College of Osteopathic Medicine and Dr. Sumit Sharma of the Russ College of Engineering and Technology, with major simulation work led by Ph.D. student Hemant Nagar. Ohio University said the team used computer modeling to identify a receptor movement that had not previously been seen.

What does the growth hormone patent cover?

The patent application describes possible changes to growth hormone-based therapeutics, according to Ohio University. Those changes could support future drugs that either increase growth hormone activity or suppress it, depending on the disease being treated.

Growth hormone deficiency can affect children who need help stimulating growth. Acromegaly is a rare condition caused by excess growth hormone, and Ohio University said it can enlarge bones, organs and soft tissues.

Kopchick’s earlier research helped produce a modified human growth hormone that became an FDA-approved treatment for acromegaly, the university said. That drug works as an antagonist, meaning it blocks excessive growth hormone activity rather than promoting growth.

How did the researchers find the mechanism?

Sharma’s group used high-performance computing to model how growth hormone interacts with its receptor. Ohio University said the proteins involved each contain more than 600 amino acids, with many atoms that must be tracked as they move and affect one another.

The team began with experimentally determined protein structures, added nearly 5,000 water molecules around the complex and simulated atomic movement at body temperature. Nagar carried out simulations that followed movement in femtosecond increments, or quadrillionths of a second, the university said.

By comparing natural growth hormone with the modified therapeutic form, the researchers found that one amino acid in the receptor changes direction and moves out of its original position, according to Sharma. That shift breaks one of the stabilizing interactions between the hormone and receptor.

Ohio University said natural growth hormone normally forms three strong ionic and hydrogen-bond interactions with its receptor. In the simulation, the receptor change reduced those stabilizing bonds from three to two, giving the team a molecular explanation for why the therapeutic version blocks activity.

The work required 72 separate simulations to assess the energy behind the receptor’s structural changes, according to the university. Each simulation produced 15 million molecular configurations, leaving the researchers with millions of snapshots to analyze.

What could it mean for patients?

Kopchick said understanding the receptor interactions gives researchers a way to design molecules with greater potency. Ohio University said that could point toward growth hormone therapies requiring fewer doses for some patients with deficiency, or more effective antagonists for people with acromegaly and related disorders.

The findings have not yet produced a new approved treatment. The university said the team is continuing additional simulations and preparing a scientific manuscript, while hoping the patent draws interest from industry partners that could license the technology.

Nagar is listed first on the patent and manuscript, according to Sharma. Ohio University said the project also shows how computational science can guide biomedical research before compounds are made and tested in the laboratory.

This story draws on original reporting from Medical Xpress.