Make your own free website on Tripod.com
Sock's Toxicity And Drugs In RA:
Research
Home | Strategies | Life | Summary | Case Histories | Coping With Pain | Side Effects | Herbs | Supplements | Symptoms | Musculoskeletal | Disease Process | Chronic Pain | Management | Effects | Arthritis | Updates | Research | Alerts | Enbrel | Remicade | Arava | Surgery | Lab Tests | Treatment | Clinical Trials | Physical Care. | NSAIDs | Joint Injection | DMARDs | Factors | Steriods

Biological response modifiers act by binding TNF a dominant cytokine that plays a prominent role in inflammation which is responsible for the pain and swelling seen in RA patients.After a connection between TNF and joint erosion was established by research,scientists were able to engineer a TNF antibody (Remicade) that destroys TNF,and in the case of Enbrel (protein) "sops up" excessive TNF.
 
Biotechnology is the industry that has found ways to create new drugs from molecules that naturally exist in the human body. It is a type of technology that has allowed researchers to identify how disease states normally occur,and how they can actually devise drugs to treat disease states that was not possible in the past.
 
Biologic drugs are the genes, proteins, or cells that are found to be involved in disease environments that can be controlled, to use in attacking and help preventing the disease.
 
A great many of these products are produced in the body and re- produced in minute amounts-to make them in sufficient amounts so that they can be used for clinically testing-they have to use what is called recombient genetic engineering.
 
What scientists do with that content,is to isolate the gene that is providing the information to the cells by which these complex molecules are formed. That gene is tailored,and divided in a smaller organism-the machinery by which genes are translated into complex molecules are known as proteins is common to all organism in the planet.
 
Scientists harness that knowledge to put the gene that encodes TNF receptor-into a cell or another organism to control to a much greater extent for the production of these biologics.   A conventional drug like methotrexate,may be composed of 20 carbon atoms and a bio- technology  drug is composed of thousands of carbon atoms that are put together to create these molecular complexities.
 
The major reason that cytokines (TNF & IL-1) are the appropiate targets for biologic therapy is that they're found in excess amounts in people with rheumatoid arthritis. What happens,is they get painful but very swollen joints. And their joints,when felt,they feel like bread-dough:they're squishy.
 
That squishiness or "bread-dough" feeling is actually the joint lining,which normally,in people without RA,a microscope is required to see,and normally can't be felt. In RA patients,it becomes very thick,and this thick joint lining then starts causing the pain and associated inflammation,and eats away at the bone and cartilage. Rheumatologists are trained at medical school to feel this manisfestation.
 
When this thick synovium or joint lining is analyzed,it's enriched with all of those little proteins or cytokines,and that's why targetting is important .Those cytokines are not seen in patients with many other arthritic diseases,including Osteoarthritis. 
 
The two main cytokines,or proteins,or "e-mails" of the immune system are TNF (tumour necrosis factor) and IL-1 (interleukin-1) Both of these have been demonstrated to be increased,in people with RA. That is why it was chosen as one of the proteins to target through bio-technology  and the use of genetic engineering.
 
One of the advantages of biologic drugs (BRMs)is they act specifically to neutralize cytokine proteins,and unlike traditional DMARDs,they are not processed by the organs of the human body,(stomach) resulting in potentially less side effects.
 
Inflazyme Pharmaceuticals LTD. recently announced that it has received approval in the U.K. to start two separate Phase 1 human clinical trials with two new oral anti-inflammatory compounds: IPL550,260 and IPL512,602. IPL550,269 and IPL512,602 are different compounds that have been derived from a new class of leukocyte suppressing  compounds discovered and developed by scientists at Inflazyme.
 
According to a company release,in pre-clinical studies,compounds in the class, exhibit a general anti-inflammatory effect via inhibition of leukocyte accumulation at the inflammatory site.
 
"The Phase 1 clinical studies are designed to study pharmacokinetics, safety and tolerability of these new drugs in human volunteers," said Ian McBeath,President and CEO of Inflazyme Pharmaceuticals Ltd. "At present we are developing these new molecules as general anti-inflammatory agents," added McBeath,"however,upon completion of concument ongoing clinical trials,we will announce specific disease indications prior to the commencement of Phase 11 trials".
 
"Leukocytes are an important component of the inflammatory process," said McBeath. An inflammatory response is provoked when an insult occurs to a tissue. Leukocytes move from the blood to the inflammatory site where they release mediators that contribute to the damage and pathology of diseases such as asthma,rheumatoid arthritis,inflammatory bowel disease,psoriasis,mutiple sclerosis and others. By inhibiting the process of leukocyte infilteration,Inflazyme's compounds may have application in a broad range of diseases.
 
Ongoing studies of a host of biological inhibitors,which may be used alone or in combination with currently available medications,appear extremely promising. As with gout, rheumatologists should now be able to subdue rheumatoid arthritis in the vast majority of cases.
 
In addition to these therapeutic advances,genetic profiling of patients at the time of diagnosis (although costly) may well become the future gold standard for establishing an optimal regimen from the onset.

Researchers at Stanford University Medical Center have found that selective COX-2 inhibitors – a class of medications widely prescribed for painful inflammatory conditions such as osteoarthritis and rheumatoid arthritis - interfere with the healing process after a bone fracture or cementless joint implant surgery.
 
Their findings, published in the November issue of the Journal of Orthopaedic Research, suggest that patients who regularly take COX-2 inhibitors should switch to a different medication, such as acetaminophen or codeine derivatives, following a bone fracture or cementless implant.
 
The study, conducted in rabbits, also suggests that physicians should consider changing prescribing patterns since many doctors commonly prescribe anti-inflammatory drugs including COX-2 inhibitors under the very circumstances in which the drugs should be avoided.
 
"It's very common. You break a bone and go to the ER. The doctor sets it in a splint and prescribes one of these anti-inflammatory drugs (including COX-2 inhibitors) for pain," said Dr. Stuart Goodman, professor of orthopaedic surgery at the Stanford School of Medicine and lead author of the study. "We now know that could actually delay healing."
 
According to a Stanford release, researchers confirmed years ago that nonspecific NSAIDS inhibited bone growth and healing, but the Stanford study is among the first to show that COX-2 inhibitors have the same effect.
 
In tests with rabbits, the researchers found that while the tissue in the control group contained 24.8 percent and 29.9 percent new bone growth, the tissue harvested after the rabbits consumed naproxen and rofecoxib contained significantly less – 15.9 percent and 18.5 percent respectively.
 
The difference in new bone growth associated with the two drugs was statistically insignificant; suggesting the COX-2 inhibitor impeded new bone growth as much as the nonspecific NSAID.
 
While acknowledging the limitations of animal research, Goodman said this study "has great applicability to humans, because the healing process is virtually the same" for rabbit and human bones. Goodman is having his own patients avoid COX-2 inhibitors for six weeks after a fracture or joint implant, and he recommends other physicians do the same. "This research has very practical applications."
 
Goodman said his recommended six-week "time-out" period is an educated guess, because his study didn't address how long the bone-growth-suppressing effects of COX-2 inhibitors last. To answer that question, Goodman and his colleagues recently began a follow-up study

Researchers funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) have found that knee malaignment is a key risk factor in the knee progression of knee osteoarthritis (OA).
 
According to Nortwestern University investigator Leena Sharma,MD,and her colleagues,participants in th Mechanical Factors in Arthritis of the Knee (MAK)  study with more severe malalignment when the study began,showed greater decline in physical function after an 18 month period. The scientists also found that severe malalignment was associated with greater subsequent loss of knee joint space. Bow-legged knee alignment was associated with a greater chance of OA progression in the inner side of the knee,while knock-kneed alignment increased the chance of OA progression on the outer side of the knee.
 
The authors state that the MAK study is the first of its kind to demonstrate knee alignment as a factor in the progression of knee osteoarthritis over an 18-month period and it suggests a potential benefit of future interventions to reduce stress caused by knee misalignment.
 
According to the authors,the risk of disability attributetable to knee OA alone is greater then that due to any other medical condition in people age 65 and over. As the population swells with graying baby boomers,vast numbers of people will experience pain and decreased function associated with osteoarthritis.

In Ottawa,Canada,a twenty-three-year-old woman,suffering from juvenile rheumatoid arthritis that had virtually attacked every joint in her body,had not gotten any relief despite having used every available medication (biologics included ) She became the first person in Canada to receive a stem cell transplant for RA.
 
Doctors at the Ottawa hospital (www.ogh.on.ca ) harvested stem cells from her blood,cleansed them of T cells,and,after obliterating her bone marrow,gave her back the concentrated,purified stem cell in March 1999.
 
A year later she was leading a normal life,virtually free of the pain that she had endured for years. Her blood tests,including those that reflect inflammation,were,according to her physician,Dr. Robert McKendry, "absolutely normal". He points out,however,that she was not in total remission from her disease because she had several tender joints.

Implants:
 
Avanta Orthopaedics Corporation announced that on  8/28/01, the FDA granted it Humanitarian Device Exemption (HDE) status for its Avanta Metacarpophalangeal (MCP) Implant Prothesis. The clearance marks the first for a semi-constrained MCP device in the U.S.
 
The MCP, composed of a cobalt chrome alloy and polethylene represents a new generation of replacements for the joints in the hand. "Before this clearance the only implants available to patients were flexible silicone implants," noted Dr. William P. Cooney III a Mayo Clinic orthopaedic hand surgeon and designer with Dr.Ronald Linschield of the new device. "While silicone implants served patients reasonably well they did not offer good stability and after seven or eight years they often failed".
 
The Avanta MCP should provide increased longevity over the currently marked silicone devices,while also relieving pain and restoring near normal hand function in certain patients. "Because the implant better duplicates the anatomy of the normal joint,it allows for ligaments to be repaired,tendon mechanisms to be rebalancd and other soft tissue structures to be returned to normal " explained Cooney. "As a result the implant should improve patients' range of motion and their pinch and grip strength".
 
Avanta expects to begin distribution of the MCP device in the U.S. immediately.
 
Protelax,Inc. recently filed a patent application covering its unique approach to the treatment of rheumatoid arthritis and other immune disorders. Capping two years of animal studies and extensive research with in vitro systems,the patent addresses an entirely new concept of therapy for diseases notoriously difficult to treat.
 
According a company release,the Protalex medication (PRTX-001) can actually regulate or normalize aberrant functions in cells affected by auto- immune disease. Unlike existing therapy this permits the tissues to return to a healthy functional state,slowing or stopping the inflammatory process,and potentially reversing earlier damage to structures such as joint cartilage. The patent covers the therapeutic use of PRTX-001 by oral administration or injection,in the treatment of all of the recognized immune disorders,including many of the most disabling human diseases such as lupus erythematosus, diabetes mellitus and asthma.
 
The Protalex patent forms the basis for the filing of an Investigational New Drug (IND) application for PRTX-001 with the U.S. Food and Drug Adminstration (FDA). Building on animal testing recently completed,the company expects to enter full clinical trials in a number of sites before the end of the year. These human studies will concentrate on treatment of rheumatoid arthritis.
 
Protalex President John E. Doherty commented,"The Company's discovery, directed by Dr. Paul L. Mann,has led to an entirely new approach to the treatment of this devasting disease. Thousands of people whose affliction had been thought beyond the reach of medicine  can now look foward not just to relief of symptoms,but perhaps to the reversal of their disease." After proof of PRTX-001's safety and efficacy in humans. Protalex will seek FDA approval for its introduction as a prescribed pharmaceutical agent.