Written By Kevin Kerfoot / Reviewed By Ray Spotts
Researchers with Harvard's Wyss Institute for Biologically Inspired Engineering and John A. Paulson School of Engineering and Applied Sciences have found a way around the limitations of inflammation-related antibodies to treat psoriasis by using an ionic liquid (IL) combination to deliver a small interfering RNA-based treatment directly to the skin.
This breakthrough - published in Science Advances - significantly reduces levels of inflammatory cytokines and symptoms of psoriasis without systemic side effects.
Previously, small molecule-based drugs like steroids penetrated the skin to treat the condition, but they could cause skin irritation and thinning with their efficacy decreasing over time.
The antibodies that target specific inflammation-related molecules associated with psoriasis could not be delivered via the skin and were injected using needles and syringes, which limited their acceptance and could have negative systemic side effects.
The researchers used the ionic liquids - which are essentially salts that are liquid at room temperature - to stabilize siRNAs and improve their penetration across lipid-based cell membranes and enable localized gene silencing.
The researchers created a library of different ILs, then tested combinations of them to see which had the physical and chemical properties they were looking for.
Treatment of eczema and other dermatologic skin conditions
This IL-based delivery platform can be easily scaled up and tuned to interface with a variety of therapeutic molecules, including DNA and antibodies.
It could also empower transdermal drug delivery for the treatment of other dermatologic skin conditions including eczema, and improve the long-term efficacy of therapies by targeting genes that mediate multiple disease pathways.
"Compared to other technologies that have demonstrated delivery of nucleic acids to the skin, our IL platform offers unique opportunities in terms of tunability, an excellent safety profile, and economical scale-up," says first author Abhirup Mandal, Ph.D., a former Postdoctoral Fellow at the Wyss Institute and SEAS who is now a Senior Research Scientist at CAGE Bio.
"We think that effective topical delivery of macromolecules will revolutionize the treatment options for debilitating dermatological disorders like psoriasis."
"Topical creams have been used to treat skin conditions for hundreds of years, but the skin is a very effective barrier against most substances, which limits their effectiveness,” added corresponding author Samir Mitragotri, Ph.D., a Core Faculty member at the Wyss Institute and the Hiller Professor of Bioengineering and Hansjörg Wyss Professor of Biologically Inspired Engineering at SEAS.
“Being able to bridge that barrier to deliver nucleic acid therapeutics directly to skin cells is a huge accomplishment in the quest for targeted, effective therapeutics,”
"Many of the innovations that biologists have been using in research for years have significant clinical potential, but most haven't achieved it because of fundamental limiting factors such as, in this case, the barrier posed by the skin,” added Wyss Institute's Founding Director and co-author Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and Professor of Bioengineering at SEAS.
“This creative solution to this drug delivery problem holds great promise for enabling a new class of effective treatments that are long overdue."
Psoriasis drug a potential treatment for osteosarcoma
A treatment for psoriasis could be repurposed to treat a rare but aggressive form of youth cancer known as osteosarcoma, according to recent findings from the Garvan Institute of Medical Research.
The findings – published in Cancer Discovery - uncover an opportunity to repurpose an existing medication and bring new hope to those suffering from osteosarcoma. Its five-year survival rate remains as low as 65 percent.
"There has been no real advance in treatments for this form of cancer in four decades - we have uncovered a new target that we know can be modulated with existing therapy," says senior author Professor David Thomas, Garvan Cancer Research Theme Leader and Director of the Kinghorn Cancer Centre.
"We hope our findings will lead to clinical trials that will provide better outcomes for patients with this rare form of cancer."
"Our search for new potential treatments for osteosarcoma began in 2013 when we investigated genetic risk factors for this form of cancer," says first author Dr. Maya Kansara, who leads the Immunobiology of Cancer Group at Garvan.
"From genome-wide association studies conducted with the U.S. National Institutes of Health we saw that variants in a gene that encodes the protein GRM4 were frequently associated with osteosarcoma.
In a mouse model of osteosarcoma, we investigated the role of GRM4, as well as a number of immune molecules, the production of which is regulated by GRM4," says Kansaras. "In our model, we discovered that the inflammatory molecule IL23 was critical to osteosarcoma formation and progression."
Therapies targeting IL23 have been investigated extensively for a number of autoimmune diseases, including arthritis, intestinal inflammation and the skin condition psoriasis.
"Drugs that block IL23 are approved and well tolerated, and on the market now for the treatment of psoriasis," Thomas added. "We are now designing clinical trials to see whether they can provide much-needed improved health outcomes for osteosarcoma patients."
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With over 30 years of writing and editing experience for newspapers, magazines and corporate communications, Kevin Kerfoot writes about natural health, nutrition, skincare and oral hygiene for Trusted Health Products’ natural health blog and newsletters.
Founder Ray Spotts has a passion for all things natural and has made a life study of nature as it relates to health and well-being. Ray became a forerunner bringing products to market that are extraordinarily effective and free from potentially harmful chemicals and additives. For this reason Ray formed Trusted Health Products, a company you can trust for clean, effective, and healthy products. Ray is an organic gardener, likes fishing, hiking, and teaching and mentoring people to start new businesses. You can get his book for free, “How To Succeed In Business Based On God’s Word,” at www.rayspotts.com.