New class of anti-arthritis drugs effectively treats multiple inflammatory diseases

July 10, 2014

Inflammatory diseases can occur simultaneously in distinct sites in the same patient, complicating treatment because a medication effective for one disorder may exacerbate the other. One such example is the anti-arthritic medication dexamethasone, which alleviates joint disease but can worsen periodontal bone disease. A study in the August issue of The American Journal of Pathology highlights the effects of a new class of anti-arthritic drugs, specifically DTrp8-ɣMSH (DTrp), that acts via the melanocortin (MC) system to reduce both arthritic joint inflammation and periodontitis.

"This research, a joint program with the Universidade Federal de Minas Gerais in Brazil, indicates that MC receptor agonists, possibly better if selective for MC3, represent a novel class of anti-arthritic therapeutics able to target without aggravating unwanted effects on distant organs and tissues," says Mauro Perretti, PhD, of Queen Mary University of London, Barts, and The London School of Medicine and Dentistry (UK).

More than 60 years ago, adrenocorticotropic hormone (ACTH) was shown to be effective for treating rheumatoid and gouty arthritis, yet its current clinical use is very sporadic. It is now appreciated that some of the anti-inflammatory actions of ACTH are mediated via the peripheral MC system on MC receptors expressed in , fibroblasts, and immune cells. Research has shown that activation of MC receptors by ACTH or other MC peptides can lead to a variety of protective actions against , including increased matrix deposition, reduced osteoclast activation, and enhanced proliferation of bone-forming cells.

In this study, researchers first determined whether mice that were induced with experimental arthritis also manifested bone loss in the alveolar (tooth socket) bone. They found that bone loss in the jaw correlated with the severity of localized inflammation in the joints of the mice.

They next compared the effects of a peptide that selectively activates MC3 receptors in mice on both arthritis and alveolar bone loss, and compared the effects to other known medications. The glucocorticoid dexamethasone exerted potent anti-arthritic effect, which were, however, inversely correlated with protection against bone loss. This was markedly distinct from the effect seen with DTrp, which showed a highly positive correlation between clinical score and bone loss (ie reduced bone loss associated with better anti-arthritic effect). Calcitonin had little effect on arthritis but did protect against alveolar bone loss. "This finding is of relevance as prolonged steroid therapy is associated with , osteoporosis, and fractures; melanocortin-based therapeutics could spare these unwanted actions," says Dr. Perretti.

"DTrp could be viewed as a starting point for a new class of bone-sparing anti-arthritic agents," says John L. Wallace, PhD, MBA, of the Department of Physiology and Pharmacology, University of Calgary, Calgary, Alberta, Canada and University of Toronto, in a commentary on these findings. "This study highlights the continued value of simpler and cheaper (for both the maker and the end-user) approaches to drug development, harnessing the potential of endogenous anti-inflammatory mechanisms."

According to Dr. Wallace, drugs that harness endogenous anti-inflammatory mechanisms like the MC system offer a number of advantages: they produce a wide range of anti-inflammatory effects, promote the healing of injured tissue, and are potentially associated with very few adverse effects. He comments that these medications "hold out significant promise for safely treating a wide range of inflammatory disorders including, like MC3 agonists, co-existing in the same patient."

Explore further: Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

More information: "Association between Periodontal Disease and Inflammatory Arthritis Reveals Modulatory Functions by Melanocortin Receptor Type 3," by Trinidad Montero-Melendez, Mila Fernandes Moreira Madeira, Lucy V. Norling, Asil Alsam, Michael A. Curtis, Tarcília Aparecida da Silva, and Mauro Perretti. dx.doi.org/10.1016/j.ajpath.2014.04.009

Related Stories

Choloroquine reduces formation of bone resorbing cells in murine osteoporosis

December 9, 2013
Bone homeostasis requires precise balance between deposition of new bone by osteoblasts and resorption of old bone by osteoclasts. Bone diseases, including osteoporosis and rheumatoid arthritis, are the result of increased ...

Research shows bone loss causes joint pain from alphaviral diseases

April 15, 2014
(Medical Xpress)—Arthritogenic alphaviruses such as Ross River virus (RRV) cause disabling joint pain. To understand what causes this pain, Suresh Mahalingam of Griffith University in Australia and his team studied how ...

Prolactin reduces arthritis inflammation

August 1, 2013
Inflammatory joint diseases such as rheumatoid arthritis are the result of cartilage damage and loss. Chondrocytes are the only cells that are found in cartilage and their death is linked to decreased cartilage health.

Protein could be key for drugs that promote bone growth

October 15, 2012
Georgia Health Sciences University researchers have developed a mouse that errs on the side of making bone rather than fat, which could eventually lead to better drugs to treat inflammatory diseases such as rheumatoid arthritis.

Researcher examines the relationship between gum disease and arthritis

October 16, 2012
Adelaide scientists have found that mice with gum disease develop worse arthritis.

Recommended for you

Targeting 'broken' metabolism in immune cells reduces inflammatory disease

July 12, 2017
The team, led by researchers at Imperial College London, Queen Mary University of London and Ergon Pharmaceuticals, believes the approach could offer new hope in the treatment of inflammatory conditions like arthritis, autoimmune ...

A perturbed skin microbiome can be 'contagious' and promote inflammation, study finds

June 29, 2017
Even in healthy individuals, the skin plays host to a menagerie of bacteria, fungi and viruses. Growing scientific evidence suggests that this lively community, collectively known as the skin microbiome, serves an important ...

Inflammatory bowel disease: Scientists zoom in on genetic culprits

June 28, 2017
Scientists have closed in on specific genes responsible for Inflammatory Bowel Disease (IBD) from a list of over 600 genes that were suspects for the disease. The team from the Wellcome Trust Sanger Institute and their collaborators ...

Trials show unique stem cells a potential asthma treatment

June 28, 2017
A study led by scientists at Monash University has shown that a new therapy developed through stem cell technology holds promise as a treatment for chronic asthma.

Researchers find piece in inflammatory disease puzzle

May 23, 2017
Inflammation is the process by which the body responds to injury or infection but when this process becomes out of control it can cause disease. Monash Biomedicine Discovery Institute (BDI) researchers, in collaboration with ...

Researchers reveal potential target for the treatment of skin inflammation in eczema and psoriasis

May 22, 2017
Superficially, psoriasis and atopic dermatitis may appear similar but their commonalities are only skin deep. Atopic dermatitis, also known as eczema, is primarily driven by an allergic reaction, while psoriasis is considered ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.