Repurposing existing FDA-approved drugs for alternative treatments offers a faster route to introducing new therapies.
In a pioneering effort, researchers from Karolinska Institutet in Sweden have repurposed a cancer drug to combat neuroinflammatory diseases, such as multiple sclerosis (MS).
Additionally, they have developed a novel drug carrier for efficient drug delivery to target myeloid cells. These pre-clinical findings have been detailed in a paper published in the EMBO Reports journal.
Microglia: A Potential Therapeutic Target
Microglia, a type of macrophage specific to the central nervous system, play a critical role in several chronic neurodegenerative conditions such as MS, Alzheimer’s disease, and amyotrophic lateral sclerosis (ALS).
Dysfunctional microglia can exacerbate these diseases. Hence, altering the activation of these harmful microglia presents an appealing therapeutic approach.
As Professor Bob Harris at the Karolinska Institutet points out, “The biotechnology industry has realized the potential for microglia-targeting strategies”.
Repurposing existing drugs could potentially halve the time required to approve a new medicine, compared to novel drug discovery programs that can span up to 20 years.
A New Role for Old Drugs
The researchers selected a Topoisomerase 1 (TOP1) inhibitor for their study through an in silico drug screening to identify candidates for modulating microglia.
They found that TOP1 was highly expressed in neuroinflammatory conditions both in mouse models and in tissues from MS patients.
The team used camptothecin (CPT) and its FDA-approved analogue topotecan (TPT), both TOP1 inhibitors, to reduce inflammatory responses in microglia and macrophages in in vitro cultures.
These drugs also alleviated neuroinflammatory diseases in vivo.
In terms of repurposing drugs, first author Keying Zhu emphasizes that “data-mining of open access databases is an approach that is both time and economically efficient”.
The team identified four compounds that proved promising for further investigation. One of these demonstrated a significant therapeutic effect in their experimental model of MS.
A Novel Drug Carrier: MyloGami
The researchers also developed a nanosystem using β-glucan-coated DNA origami (MyloGami) loaded with TPT (TopoGami) to target microglia and macrophages specifically.
This effort was carried out in collaboration with Professor Björn Högberg’s group at the Department of Medical Biochemistry and Biophysics.
MyloGami demonstrated enhanced specificity for myeloid cells and also protected the DNA origami scaffold from degradation.
The use of TopoGami for myeloid-specific TOP1 inhibition significantly suppressed the inflammatory response in microglia and reduced MS-like disease progression.
The repurposing of a cancer drug and the development of a new drug carrier system demonstrate the possibilities of innovative therapeutic approaches to neuroinflammatory diseases.
This approach of reusing existing drugs could potentially reduce the time and cost of introducing effective treatments, providing new hope for patients suffering from debilitating diseases such as multiple sclerosis.
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The study was published in EMBO reports.
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