Effective Stem Cell-Based Treatment for Lupus


Chinese physicians and stem cell researchers from Shenzhen, China have reported on their clinical trial that treated 40 patients with severe and refractory lupus systemic erythematosus with mesenchymal stem cells isolated from umbilical cord.  This 40-patient, multicenter study targeted patients with active and difficult-to-treat lupus.

Systemic lupus erythematosus (SLE), which is also simply known as lupus, is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue.  Lupus can affect the skin, joints, kidneys, brain, or even other organs.

What causes lupus is uncertain, but tissue damage seems to predispose some people to the onset of lupus.  Lupus commonly affects women than men, and it can occur at any age.  It most commonly appears most often in people between the ages of 10 and 50, and African-Americans and Asians are affected more often than people from other ethnic groups.  Particular drugs have also been linked to the onset of lupus or lupus-like conditions (e.g., isoniazid, hydralazine, procainamide, and less commonly anti-seizure medicines, capoten, chlorpromazine, etanercept, infliximab, methyldopa, minocycline, penacillamine, quinidine, and sulfasalazine).

The symptoms of lupus vary tremendously and they usually come and go.  Almost all lupus patients have some joint pain and swelling, and some develop arthritis.  Typically the joints of the fingers, hands, wrists, and knees are most often affected.  Other symptoms include chest pain when taking a deep breath, fatigue, fever, general discomfort, uneasiness, or ill feeling (malaise), hair loss, mouth sores, swollen lymph nodes, and sensitivity to sunlight.  Also, a specific type of skin rash known as a “butterfly” rash occurs in about half of lupus patients.  The butterfly rash is most often seen over the cheeks and bridge of the nose, but can be widespread and gets worse in sunlight.  Some people have only skin symptoms and have what is known as discoid lupus. 

Chronic lupus usually becomes concentrated in specific organs, which can cause secondary symptoms.  These symptoms can include:

1.  Brain and nervous system: headaches, numbness, tingling, seizures, vision problems, personality changes.

2.  Digestive tract: abdominal pain, nausea, and vomiting, and the symptoms of liver failure.

3.  Heart: abnormal heart rhythms (arrhythmias).

4.  Lung: coughing up blood and difficulty breathing.

5.  Skin: patchy skin color, fingers that change color when cold (Raynaud’s phenomenon)

To treat lupus, powerful anti-inflammatory drugs are usually used.  These include systemic steroids such as prednisone (Deltasone and others), hydrocortisone, methylprednisolone (Medrol and others), or dexamethasone (Decadron and others).  Other drugs include nonsteroidal anti-inflammatory drugs (NSAIDS), such as ibuprofen (Advil, Motrin and other brand names) or naproxen (Aleve, Naprosyn and others).  However, other drugs include antimalarial drugs such as hydroxychloroquine (Plaquenil), chloroquine (Aralen), or quinacrine. Recent studies suggest that lupus patients treated with antimalarial medications have less active disease and less organ damage over time. Therefore, many experts now recommend antimalarial treatment for all patients with systemic lupus unless they cannot tolerate the medication. If these do not work, then the “big guns” include immunosuppressives, such as azathioprine (Imuran), cyclophosphamide (Cytoxan, Neosar), mycophenolate mofetil (CellCept), or belimumab (Benlysta) and Methotrexate (Rheumatrex, Folex, Methotrexate LPF).  These drugs have long lists of side effects and drug interactions.  Even then, some patients are not helped by these drugs.

Thus more efficacious and safe ways to treat recalcitrant cases of lupus have included stem cell treatments.  In particular, mesenchymal stem cells and their ability to suppress inflammation.  To that end, several pre-clinical and clinical trials have tested mesenchymal stem cells from bone marrow, fat and umbilical cord to reduce the chronic inflammation associated with particular autoimmune diseases (see P Connick, et al., Lancet Neurol. 2012 Feb;11(2):150-6; MM Bonab, et al., Curr Stem Cell Res Ther. 2012 Nov;7(6):407-14; J Voswinkel, et al., Immunol Res. 2013 Jul;56(2-3):241-8; P Connick P, et al., Trials. 2011 Mar 2;12:62; D Karussis, et al., Arch Neurol. 2010 Oct;67(10):1187-94; B Yamout, et al., J Neuroimmunol. 2010 Oct 8;227(1-2):185-9).

This new Chinese trial provides some very interesting and welcome data on the use of mesenchymal stem cells from umbilical cord to treat lupus.

Dr. Xiang Hu, who founded the biotechnology company Beike, said, “We are pleased with the results we have seen in our clinical trial.  While some severe cases experienced relapse after 6 months, the results show a markedly improved quality of life expectation.  This is a big step forward in combating autoimmune disease.  We will now be looking to further our SLE research efforts to find even better results.”

The forty patients who participated in the study were recruited from four centers in China.  The umbilical cord-derived mesenchymal stem cells used in the study were processed by Beike Biotech’s scientists at the company’s new state-of-the-art Jiangsu Stem Cell Regenerative Medicine Facility in Taizhou, China.  Stem cells from sources other than the patient’s own body are known as allogeneic stem cells, and these forty patients, all of whom have refractory lupus were infused with umbilical cord mesenchymal stem cells intravenously at the beginning of the study and one week later.  To score each patient’s disease progression, a clinical test called a SLEDAI or Systemic Lupus Erythematosus Disease Activity score.  The SLEDAI score results from a compilation of multiple clinical and laboratory tests.

After 6 months, all patients showed significant improvement in their SLEDAI scores, but after six months, several patients experienced relapse, which required a repeat treatment with mesenchymal stem cells. Also, the safety profile of these cells was superior to many of the drugs used to treat lupus.

This study is suggests that the mesenchymal stem cells suppress active lupus without causing severe adverse effects.  However, in order to show that definitively, a double-blinded, placebo-controlled study must be conducted.  Also, trying to provide longer periods of relief rather than just six months of relief is another factor that further work will hopefully address.

Advertisements

Published by

mburatov

Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).

One thought on “Effective Stem Cell-Based Treatment for Lupus”

Comments are closed.