UConn School of Pharmacy

Dental Researchers Attack Painful Chemo Side Effect

chemo patient

An estimated 400,000 U.S. patients undergoing chemotherapy and radiation therapy each year develop painful mouth sores known as oral mucositis. Researchers across UConn are attacking this common side effect from several angles, with one team working to understand the root causes of the ulcers and another developing a better way to treat them.

Cancer drugs break down the mucous membranes lining the mouth, called oral mucosa, inducing painful lesions that can cause difficulty talking, swallowing, and eating. The pain can become so severe that patients require feeding intravenously or through a stomach tube. Other risks to patients include slower healing, decreased resistance to infection, and general failure to thrive. Secondary infection and potentially life-threatening systemic sepsis have also been reported.

While the pain that oral mucositis causes is certainly of great concern, perhaps the most harmful impact occurs when patients are in such extreme agony that their attending physicians have no choice but to prescribe undesirable dose reductions or treatment breaks in cancer therapy.

One UConn School of Dental Medicine research team published in Springer Nature’s Microbiome the most comprehensive study to date about the patho-physiology of oral mucositis in humans due to the effects of chemotherapy.

The team, led by Dr. Patricia Diaz, associate professor in the Department of Oral Health and Diagnostic Sciences, found that patients who developed the most severe lesions showed suppression of beneficial mouth bacteria and outgrowth of harmful ones.

Further studies are needed to understand which specific microbiome components are detrimental and in what manner they affect the oral mucosa’s ability to withstand a chemotherapy challenge.

Meanwhile, Dr. Rajesh Lalla, professor of dental medicine, is collaborating with UConn Board of Trustees Distinguished Professor of Pharmaceutical Sciences Diane J. Burgess, graduate student Tingting Li, and drug design firm Cellix Bio to develop a new, long-acting topical anesthetic that he hopes will someday replace current methods of treating oral mucositis.

The current first-line therapy at most U.S. hospitals is a mouth rinse containing the local anesthetic lidocaine, providing about 30 minutes of relief. The rinse numbs the entire mouth instead of focusing specifically on the sores, which poses safety concerns since it can inhibit the swallowing reflex. Patients are also often prescribed systemic opioids to treat the pain.

The team has developed an innovative formulation and novel patented compound that allows a long-acting topical anesthetic to be applied directly to sores. The researchers expect the more potent anesthetic should relieve pain for about four hours, eight times as long as the standard mouth rinse.
The compound also exhibits antimicrobial and anti-inflammatory effects naturally delivered by the medium chain fatty acid, which could reduce the severity of lesions from oral mucositis, says Lalla.

Lalla and his collaborators believe they are one to two years away from clinical trials in humans.

Lab Notes – Fall 2016

‘Morrbid’ RNA Could Be Key to Asthma Treatment

No.2 Pencil eraser erasing a piece of an RNA strand

Researchers have discovered a potential therapeutic target for inflammatory disorders that are characterized by abnormal myeloid cell lifespan, such as asthma, Churg-Strauss syndrome, and hypereosinophilic syndrome. Investigators including Adam Williams of UConn Health and The Jackson Laboratory named the novel long non-coding RNA ‘Morrbid’ (Myeloid RNA Regulator of Bim-Induced Death). They discovered that Morrbid tightly controls how long circulating myeloid cells live — which is key to maintaining the balance between fighting infection and exacerbating inflammation — by overriding a signaling mechanism that prevents premature immune cell death. In mice, deleting the gene helped protect them against inflammation and immunopathology. The findings were published online in Nature, Aug. 15, 2016.


Parents Living Longer is Good News for Offspring, Study Says

Father and young son laugh together and hug

A new study led by the University of Exeter and co-authored by the UConn Center on Aging, among other international contributors, shows that how long a person’s parents live can help predict how long the offspring will live, and how healthy the child will be as he or she ages. The study of 186,000 participants, aged 55 to 73 years and followed for up to eight years, is the largest of its kind. It found that a person’s chance of survival increased by 17 percent for each decade that at least one parent lived beyond age 70, and that those with longer-lived parents had lower rates of heart disease and other circulatory conditions, as well as cancer. The study was published in the Journal of the American College of Cardiology, Aug. 15, 2016.


PRP Limits Ill Effects of Osteoarthritis Treatment

red blood cells

Giving platelet-rich plasma (PRP) to patients undergoing treatment for osteoarthritis may limit the negative effects of the drugs used to manage their symptoms, according to a new study led by Dr. Augustus Mazzocca, director of the UConn Musculoskeletal Institute, and the University of Pittsburgh Medical Center. Osteoarthritis is the most common chronic condition of the joints, causing pain, stiffness, and swelling in approximately 27 million Americans. Powerful anti-inflammatory medicines and local anesthetics relieve pain and improve range of motion, but can also lead to tissue degeneration. In the study, published in the August issue of The American Journal of Sports Medicine, researchers found combining PRP with these treatments significantly reduced their toxic effect on the cells and even improved their proliferation.


Bath Salts 101: Pharmacist Explains Party Drugs

Synthetic party drugs with dangerous hallucinogenic properties, such as those sold commercially as “bath salts,” continue to pose a significant public health risk around the country. C. Michael White — head of the Department of Pharmacy Practice in UConn’s School of Pharmacy — published a comprehensive review of synthetic cathinones in the June 2016 issue of The Journal of Clinical Pharmacology to help clinicians recognize signs of abuse and properly treat patients with adverse events, ranging from psychosis to heart disease, from the drugs. This is the third in a series of articles on drugs including molly/ecstasy and GHB that he wrote to support clinicians. He is currently working on an assessment of synthetic marijuana.

dirty spoon holds 'bath salt' drug