By incorporating a gene-suppressing drug into an over-the-counter gel, researchers at Albert Einstein College of Medicine and their colleagues cut healing time by half and significantly improved healing outcomes compared to control treatments.
Results from the combination therapy, which was tested in mice, were published online today in Advances in Wound Care,
“Not only did wound healing occur more rapidly and completely, but actual regeneration occurred, with hair follicles and the skin’s supportive collagen network restored in wounded skin—clinically important improvements that are unprecedented in wound care,” says senior author David J. Sharp, Ph.D., professor of physiology & biophysics at Einstein. “We foresee this therapy having broad application for all sorts of wounds, from playground cuts to battlefield injuries to chronic wounds.”
Chronic wounds alone affect 6.5 million Americans and cost $25 billion in annual healthcare costs. Over the past several decades, few advances have been made in treating wounds of any type.
In 2015, Dr. Sharp and colleagues discovered that an enzyme called fidgetin-like 2 (FL2) puts the brakes on skin cells as they migrate towards wounds to heal them. He reasoned that reducing FL2 levels might enable healing cells to reach their destination faster. So he and his colleagues developed small interfering RNA molecules (siRNAs) that specifically inhibit the gene that codes for FL2. When the siRNAs were encased in nanoparticles and sprayed on skin wounds in mice, the treated wounds healed faster than untreated wounds.
In the current study, Dr. Sharp enhanced the siRNAs’ wound-healing potential by combining them with PluroGel—a protective gel that keeps wounds moist and has antimicrobial properties when applied to bandages and other wound dressings. In addition, Dr. Sharp incorporated the siRNAs into microparticles made of collagen, a naturally occurring protein that readily releases its siRNA “cargo” after coming in contact with the skin.
The FL2-siRNA/PluroGel combination was applied to mice with either skin excisions or burns. For comparison, studies involving both types of skin injuries also used two control groups: mice treated with PluroGel alone and mice treated with PluroGel plus siRNA that did not target the gene for FL2. Wounds were treated on the day of the skin excision or burn and again two, four and six days later. For 14 days following the injuries, wounds were assessed by investigators who were “blinded” as to the treatment the mice received.
On the fourth day after mice treated for excision wounds, the open wound areas of mice in the two control groups were nearly twice as large as the wound areas in mice treated with the FL2-siRNA/PluroGel combination. Several mice treated with the combination therapy also had hair follicles present in the wound zone, while no such structures were seen in the control mice.
For mice treated for burns: by 14-days post injury, the wounds of mice in both control groups were more than one-third larger than in the mice treated with the FL2-siRNA/PluroGel combination. In addition, the burn wounds of all mice treated with the FL2-siRNA/PluroGel combination had closed completely by day 14; by comparison, 25 percent and 30 percent of treated wounds in the PluroGel and PluroGel/nontarget siRNA control groups, respectively, remained unhealed at that time.
“These results show that FL2-siRNA plus PluroGel is a highly promising wound treatment,” says Adam Kramer, a Ph.D. candidate in Dr. Sharp’s lab and co-lead author. “By lowering FL2 levels in skin cells, the FL2-siRNA helps cells reach wound sites much faster than they ordinarily would—essential for minimizing scarring and preventing wounds from becoming chronic. And by hydrating wounds and inhibiting microbes, PluroGel offers important additional wound-healing benefits.”
Dr. Sharp and Brian O’Rourke, Ph.D., the paper’s co-lead author and chief scientist at MicroCures, Inc., have achieved similar success in treating skin wounds in pigs—animals with skin that closely resembles human skin. Dr. Sharp’s team plans to seek permission from the U.S. Food and Drug Administration to test their wound-healing therapy in clinical trials.
Learn more: Novel Combination Therapy Promotes Wound Healing
Receive an email update when we add a new COMBINATION THERAPY article.
The Latest on: Combination therapy
via Google News
The Latest on: Combination therapy
- Combination therapy promising against blindness-causing bacterial keratitis on November 12, 2018 at 10:04 am
Multidrug-resistant bacterial infections of the cornea are a leading cause of blindness and cannot be effectively managed with current ophthalmic antibiotics. A team of investigators has now ... […]
- Combination Therapy With Mogamulizumab Demonstrates Tolerable and Manageable AEs on November 12, 2018 at 7:50 am
Results from a two-part, phase I dose-escalation and -expansion trial involving mogamulizumab (Poteligeo) in combination with durvalumab (Imfinzi) or tremelimumab for the treatment of patients with ad... […]
- Combination Therapy Promotes Rapid Wound Healing on November 11, 2018 at 9:32 pm
A new study shows that incorporating a gene-suppressing drug into a surfactant polymer gel dressing helps wounds heal more rapidly and with higher fidelity. Researchers at Albert Einstein College of M... […]
- BRIEF-Clearside Biomedical announces Sapphire phase 3 study of combination therapy in retinal vein occlusion did not meet its primary endpoint on November 5, 2018 at 4:28 am
Nov 5 (Reuters) - Clearside Biomedical Inc: * CLEARSIDE BIOMEDICAL ANNOUNCES SAPPHIRE PHASE 3 STUDY OF COMBINATION THERAPY IN RETINAL VEIN OCCLUSION DID NOT MEET ITS PRIMARY ENDPOINT * CLEARSIDE BIOME... […]
- Clearside Biomedical Announces SAPPHIRE Phase 3 Study of Combination Therapy in Retinal Vein Occlusion Did Not Meet Its Primary Endpoint on November 5, 2018 at 4:00 am
- Company to Host Conference Call at 8:30 a.m. ET to Review the 8-Week Topline Data - ALPHARETTA, Ga., Nov. 05, 2018 (GLOBE NEWSWIRE) -- Clearside Biomedical, Inc. (NASDAQ:CLSD), a ... […]
- Charles Ryan on mCRPC Treatment: Combination Therapy - Clinical Case on November 4, 2018 at 10:54 pm
Dr. Ryan is Professor of Clinical Medicine and Urology at the UCSF Helen Diller Family Comprehensive Cancer Center where he is the Clinical Program Leader for Genitourinary Medical Oncology. He receiv... […]
- Nintedanib combination therapy no better than monotherapy in some cases of idiopathic pulmonary fibrosis on November 1, 2018 at 8:57 am
Nintedanib plus sildenafil produced the same results as ninetdanib alone in patients with idiopathic pulmonary fibrosis and diffusion capacity of the lungs for carbon monoxide of 35% or less, accordin... […]
- Priority Review Granted to Combination Therapy for Previously Untreated Subsets of Leukemia & Lymphoma on October 31, 2018 at 11:08 pm
The US Food and Drug Administration (FDA) has accepted AbbVie’s supplemental new drug application (sNDA) and granted a priority review for its combination therapy, ibrutinib (IMBRUVICA) in combination ... […]
- AbbVie (ABBV) Phase 3 Trial Evaluating Venetoclax Combination as First-Line Therapy in CLL Met its Primary Endpoint on October 31, 2018 at 1:54 pm
Get instant alerts when news breaks on your stocks. Claim your 2-week free trial to StreetInsider Premium here. AbbVie (NYSE: ABBV), a research-based global biopharmaceutical company, today announced ... […]
via Bing News