Marinomed Biotech‘s Marinosolv technology can be used to deliver pergolide to the eye, resulting in corneal healing, a mouse study suggests. This could form the basis of treatment strategies for neurotrophic keratitis (NK).
The study, “Topical Pergolide Enhance Corneal Nerve Regrowth Following Induced Corneal Abrasion,” was published in Investigative Ophthalmology & Visual Science.
Pergolide is a medication that activates dopamine receptors, particularly the receptor D1. It was originally developed to treat Parkinson’s disease, but its use in that condition is limited because systemic administration of the therapy can cause heart problems. In fact, although it is still in use in other countries, it was taken off the market in the U.S. and Canada.
Previous research has suggested that activation of D1 with pergolide can stimulate the production of nerve growth factor (NGF). This molecule promotes the growth and healing of the cornea and has been investigated as a treatment strategy for NK: For example, approved treatment Oxervate (cenegermin) works by mimicking the activity of NGF.
Thus, there is a biological rationale for using pergolide as an NK treatment. Additionally, medications applied directly to the eyes (in the form of eye drops) generally don’t get absorbed into the rest of the body, which would lower the risk of heart problems developing as a side effect.
However, pergolide does not dissolve well in water, which makes it difficult to use it in eye drops. Marinosolv is a solvent that basically makes compounds that are difficult to dissolve, like pergolide, more soluble. As such, Marinosolv could be used as a vehicle to deliver pergolide to the eyes.
“Solubilization of otherwise insoluble compounds is critical especially in eye care where compounds are washed out fast,” Bala Ambati, MD, PhD, a professor at the University of Utah and co-author of the study, said in a press release.
Ambati and his colleagues tested the effects of Marinosolv-delivered pergolide in several cell and animal models related to NK.
First, they treated chicken neurons in dishes with pergolide. This increased the length of these neurons in a dose-dependent manner, suggesting that the treatment promoted neuronal growth. Simultaneously, pergolide treatment increased NGF levels, which is consistent with the proposed mechanism of action, i.e., D1 activation leading to NGF production, which prompts neural growth and corneal healing. Chemically blocking D1 prevented these effects of pergolide treatment, also supporting the proposed mechanism of action.
They then tested Marinosolv-delivered pergolide in a mouse model of cornea injury, which is reminiscent of the kind of damage found in NK.
In these mice, treatment with Marinosolv-delivered pergolide significantly increased the regeneration of nerve fibers in the cornea. This treatment also significantly shortened the time it took for the wound at the cornea to heal.
Notably, these treatment benefits were not seen with cabergoline, a compound that preferentially activates a different dopamine receptor (D2).
These data further support pergolide as a therapy for corneal damage that acts through the proposed D1/NGS mechanism of action. It should be noted, however, that exactly how D1 activation leads to increased NGS levels isn’t fully understood — this may be an avenue for future investigations. Additional study on potential side effects and optimal dosing will also be needed.
“Pergolide was effective in enhancing corneal neural regeneration and epithelial wound healing,” the researchers wrote. “Although the entire pathway is not understood, it is apparent that pergolide could exert its effects by upregulating NGF levels, making it a potential drug candidate and a novel therapy for neurotropic keratopathy.”
Beyond pergolide specifically, these data support the use of Marinosolv as a vehicle for the delivery of difficult-to-dissolve substances.
“The new data once again show the effectiveness and manifold scope of application of our clinically validated Marinosolv platform,” said Andreas Grassauer, CEO of Marinomed Biotech.