Venom can kill, but this research proves it could help do the opposite. More specifically, some chemicals found in venom could act as a treatment for disease. These chemicals come from a deadly reptile, but with the help of Dr. Christine Beeton, venom might be able to better the lives of multitudes of people.
Dr. Beeton and her research team are looking at the chemicals found in scorpion venom as a source of potential treatment for autoimmune diseases like rheumatoid arthritis (RA).
While RA mainly affects joints in the body, it can also affect other organs. Many new drugs have improved the outcome for patients with RA, but while the drugs mainly reduce pain and inflammation, some patients have only partial response or even become resistant to the drugs. Of equal concern is the fact that the drugs prevent normal functions of white blood cells in the immune system, affecting the body’s ability to fight cancers and infections. “Our goal is to develop a new drug that treats RA without affecting white blood cells, allowing patients to combat infections and cancers,” Dr. Beeton explained.
Dr. Beeton’s three-year Arthritis Foundation-funded project, “Targeting KCa1.1 channels in synoviocytes for the treatment of RA”, looks at specialized cells in the joints called fibroblast-like synoviocytes (FLS). FLS are found in the membranes (called synovial membranes) that surround joints. In healthy joints, the synovial membranes and the FLS produce proteins and remove dead cell debris, which lubricates and maintains the joint. During RA, white blood cells attack the joints, leading to disease and pain. When white blood cells begin to attack the joints, the FLS become very active and aggressive. They begin to increase in numbers and destroy the cartilage in the joint, and some can enter the bloodstream and colonize other healthy joints.
In a previous study, Dr. Beeton and her team identified a potassium channel (called KCa1.1) on FLS from patients with RA (RA-FLS). Potassium channels act like doors on the surface of cells that regulate the ability of potassium ions to enter or leave the cell.
The team tested RA-FLS in test tubes, using a small chemical that could block the KCa1.1 channel. KCa1.1 is not found on white blood cells, so blocking this channel does not prevent the body from fighting infections. When the KCa1.1 channel was blocked, the RA-FLS were unable to move or release chemicals that damage the joints.
When they tested the KCa1.1 blocker in two different rat diseases that mimic human RA, they found that the severity of the disease was reduced but caused significant side effects because the small chemical could enter the brain and other organs. The most serious side effects included hypertension, tremors, and incontinence.
The KCa1.1 structure is a little different in each organ, which led to the idea that using a small peptide from scorpion venom to block KCa1.1 might work differently. Dr. Michael W. Pennington, a chemist on the team, chemically synthesized the KCa1.1-blocking peptide, called iberiotoxin (IbTX), from scorpion venom. The team discovered that IbTX is selective in which KCa1.1 it effects: it cannot enter the brain and, so far, has not induced incontinence in rats.
The team is currently testing how effective IbTX is in reducing the severity of disease and whether it will cause hypertension, tremors, or incontinence in two different rat models of RA. So far, the team has seen little to no tremors and no incontinence in the rats.
“This may not be our final KCa1.1 blocker,” explained Dr. Beeton. “We may need to modify it to make it even more selective. The IbTX gets into the joint because it is damaged. We think it cannot reach the small muscles cells in the bladder, but we need more testing. We would like to eventually fluorescently tag the peptide to see where it is going.”
This drug class could potentially be a therapeutic option for millions of Americans with knee OA.
Dr. Beeton is an associate professor of the department of Molecular Physiology and Biophysics at Baylor College of Medicine in Houston, Texas. She is also the Academic Director of the Cytometry and Cell Sorting Core for the Dan L. Duncan Cancer Center at the college. Her research lab is currently working on two main topics: targeting potassium channels for the treatment of chronic diseases (multiple sclerosis, rheumatoid arthritis, and type 1 myotonic dystrophy) and using antioxidant nanomaterials for the treatment autoimmune diseases (multiple sclerosis and rheumatoid arthritis) related to T‑cell response.
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