Feb
15
2020

Rheumatoid Arthritis Treatment by Regenerative Medicine

Dr. David Lans gave a talk at a conference in Las Vegas about rheumatoid arthritis treatment by regenerative medicine. This was at the 27th Annual World Congress on Anti-Aging Medicine in Las Vegas from Dec. 13 to 15th, 2019. The full title of his presentation was “Rheumatoid Arthritis, A Regenerative Medicine Approach”.

Dr. Lans is a rheumatologist and Assistant Clinical Professor of Medicine at the New York Presbyterian Lawrence Hospital, Bronxville, NY.

Introduction

Rheumatoid arthritis is a worldwide immune disorder. About 1% of the general population suffer of this illness with a female to male ratio of 3:1. Typically it can affect  the synovial membranes of all joints. To clarify, the presentation is usually symmetrical, but in 40% of all cases this systemic inflammatory disease can also involve other tissues and organs. 70% of cases have a positive rheumatoid factor (RF) in blood tests. However, a newer, more specific blood test for rheumatoid arthritis is anti-cyclic citrullinated peptide (anti-CCP). Symptoms of rheumatoid arthritis are anemia, fatigue, malaise, joint pain and joint stiffness. Inflammatory blood markers are positive.

Causes of rheumatoid arthritis

Genetic causes play an important role in the causation of rheumatoid arthritis. Over 100 genes  can increase due to genetics. Twin studies showed that the concordance rate to develop RA is only 15-20%. Certainly, this means that in order to develop RA you need a double hit: the genetic vulnerability for RA and also an environmental triggering factor. Meanwhile, here is a list of environmental risk factors:

  • Smoking
  • Gum disease (chronic gingivitis)
  • Any chronic infection
  • Dysbiosis in the gut
  • Environmental toxins
  • Heavy metal toxicity
  • Poor diet and nutrition

In other words, the common denominator to all of these environmental risk factors is the disruption of the mucosal integrity. In fact, this starts the process of chronic inflammation and autoantibodies (like RF and anti-CCP) resulting in chronic synovitis.

How inflammation travels from mucosal surfaces to the synovium of joints

Inflammation in gums, lungs or gut can travel via the blood and the lymphatic system into periarticular bone. This leads to bone and cartilage damage. Consequently, the bone destruction leads to chronic synovitis. To emphasize, Dr. Lans said that no patient with rheumatoid arthritis will develop symptoms of RA unless the autoantibodies have developed. In the same vein, there is a distinct preclinical period of RA with positive blood tests for RA, but absent clinical symptoms.

Prevention of synovitis through a preventative program

It is important to realize that because of this time relationship there is room for a preventative program where patients are taught the importance of dental hygiene. Another key point is that good health habits and nutrition are also important for prevention. When patients develop early-onset RA, the following measures often help to alleviate the development of symptoms: anti-inflammatory diet, stress management, intermittent fasting, a gut healing program, nutraceuticals like vitamin D3 and fish oil. Herbal therapies are also important like curcumin, Boswellia serrata, devil’s claw, ginger, Ashwagandha and others.

Conventional medicine approach versus the regenerative medical approach

To explain, the conventional treatment approach of rheumatoid arthritis is to induce a disease remission with drugs. To this effect doctors use anti-inflammatory drugs like ANSAIDs, disease modifying anti-rheumatic drugs (DMARDs). For example, drugs like methotrexate and sulfosalazine belong into this category. Unfortunately, the conventional drugs have many serious side effects that often make the rheumatoid arthritis patient’s condition worse.

In contrast, the integrative medicine approach to rheumatoid arthritis is to use dietary measures to reduce the inflammation. The fasting mimicking diet is able to reduce the severity of the inflammation in RA patients.

Other authors described the use of the Mediterranean diet to reduce inflammation. In addition, there are a number of regenerative methods that help improve the condition of RA patients.

Regenerative medical treatments for RA patients

Significantly, platelet rich plasma (PRP), peptides, stem cell therapy and exosomes are some of the modalities that show promise. (I’ll explain the meaning of exosomes later.) In addition, red light therapy and low-level laser therapy can help joint synovitis.

PRP provides growth factors to repair damaged tissues and is anti-inflammatory. Peptides consist of short chains of amino acids that have anti-inflammatory effects and promote healing of damaged tissues. Thymosin-alpha 1, Thymosin-beta 4, BPC-157, Melanotan II and FOXO4-DRI are examples of peptides used in patients. Special blood tests are used to monitor whether the treatment of RA is successful. These tests are: C-reactive protein, sedimentation rate (ESR) and Vectra. Vectra measures 12 protein markers that are important in RA.

More info about peptide therapy

Researchers noticed that peptides are very safe, but they are also very effective. HAP-1 seems to bind to synovial surfaces. RDG peptides work closely together with integrin-binding proteins. Together they have an anti-inflammatory effect in rheumatoid arthritis. They are capable of blocking both the inflammatory and autoimmune components of rheumatoid arthritis. Thymosin-alpha 1 is a peptide with powerful effects as an immune and inflammation modulator. Thymosin-beta 4 is promoting tissue healing. BPC-157 is a peptide with 15 amino acids. It helps with the regeneration of tissue after damage.

Melanotan II is a synthetic peptide derived from melanocortin, a pituitary hormone. It helps to suppress cytokine-meditated inflammation.

FOXO4-DRI is a peptide that stimulates the removal of senescent cells. Because of this it is called a senolytic. Researchers are still investigating FOXO4-DRI in humans and for the tissue repair effect in rheumatoid arthritis patients.

The use of stem cells in RA therapy

Another biological remedy for treating RA patients is the use of mesenchymal stem cells. In 2013 rheumatoid patients received umbilical cord stem cells to study the effect of stem cells. The clinical trial consisted of 172 patients. In the trial disease modifying anti-rheumatic drugs plus placebo were compared to disease modifying anti-rheumatic drugs plus umbilical cord stem cells (treatment group). In the treatment group inflammatory cytokines were reduced and regulatory T cells were increased. Improvement was assessed with objective clinical measures and blood tests. The improvement lasted between 3 and 6 months.

Exosome therapy from mesenchymal stem cells 

Many of the effects of stem cells are explainable by so-called exosomes. They are cell particles shed by stem cells. They contain signalling proteins (integrins), messenger RNA and many other healing substances. The bioactive effects are very diverse. Exosomes are bactericidal, antifungal, stimulate angiogenesis and stimulate tissue regeneration. They are also anti-apoptosis, anti-tumoral, anti-fibrosis, stimulate immunomodulation and cause chemoattraction.

What does that mean clinically? Exosomes suppress the release of inflammatory cytokines. Anti-inflammatory cytokines (like transforming growth factor beta or TGF-beta) are increased. Exosomes reduce the Th17 cells (T helper cells that produce the inflammatory cytokine IL-17). They also promote osteochondral regeneration, which is important for joint healing in the treatment of RA patients.

Treatment of RA using the integrative and regenerative medicine approach

  1. The physician assesses all affected joints and orders blood tests to check the inflammatory status.
  2. Identify the triggers that perpetuate the RA disease. Typically there are gut dysbiosis issues that need treatment. Sleep hygiene and stress issues require modification.
  3. Assess the need for disease modifying anti-rheumatic drugs (DMARDs); these are drugs like methotrexate, sulfosalazine and others.
  4. Peptide protocol: BPC-157: 300 micrograms once or twice daily IV; Thymosin alpha: 300 micrograms once or twice daily IV; Thymosin beta: 100 to 300 micrograms once daily IV, limit to 3-month cycle.
  5. Mesenchymal stem cell therapy and exosomes.
Rheumatoid Arthritis Treatment by Regenerative Medicine

Rheumatoid Arthritis Treatment by Regenerative Medicine

Conclusion

Rheumatoid arthritis is a common autoimmune disease, which leaves the patient disabled, if she receives no treatment for it. Conventional rheumatologist protocols treat the inflammation with various drugs, but they cause a lot of side effects.

There is an emergence of regenerative therapies that may be able to help treat the inflammation of the rheumatoid arthritis patient with less side effects. At the same time these treatments can also help to repair the damaged tissues. There is a great need for more clinical studies. Current human data are limited. Safe options to treat RA patients are mesenchymal stem cell therapy, exosome treatment and peptide therapies. The approach of the physician depends on the clinical stage the patient is in. It is common sense that early diagnosis and treatment will have better results. Also, an integrative approach has the best chance to help the patient with the least side-effects.

About Ray Schilling

Dr. Ray Schilling born in Tübingen, Germany and Graduated from Eberhard-Karls-University Medical School, Tuebingen in 1971. Once Post-doctoral cancer research position holder at the Ontario Cancer Institute in Toronto, is now a member of the American Academy of Anti-Aging Medicine (A4M).