How Stem Cell Therapy Protects Bone In Lupus


Systemic Lupus Erythematosis, otherwise known as lupus, is an autoimmune disease cause your own immune system attacking various cells and tissues in your body. Lupus patients can suffer from fatigue, joint pain and selling and show a marked increased risk or osteoporosis.

Clinical trials have established that infusions of mesenchymal stem cells (MSCs) can significantly improve the condition of lupus patients, but exactly why these cells help these patients is not completely clear. Certainly suppression of inflammation is probably part of the mechanism by which these cells help lupus patients, but how do these cells improve the bone health of lupus patients?

Songtao Shi and his team at the University of Pennsylvania have used an animal model of lupus to investigate this very question. In their hands, transplanted MSCs improve the function of bone marrow stem cells by providing a source of the FAS protein. FAS stimulates bone marrow stem cell function by means of a multi-step, epigenetic mechanism.

This work by Shi and his colleagues has implications for other cell-based treatment strategies for not only lupus, but other diseases as well.

“When we used transplanted stem cells for these diseases, we didn’t know exactly what they were doing, but saw that they were effective,” said Shi. “Now we’ve seen in a model of lupus that bone-forming mesenchymal stem cell function was rescued by a mechanism that was totally unexpected.”

In earlier work, Shi and his group showed that mesenchymal stem cell infusions can be used to treat various autoimmune diseases in particular animals models. While these were certainly highly desirable results, no one could fully understand why these cells worked as well as they did. Shi began to suspect that some sort of epigenetic mechanism was at work since the infused MSCs seemed to permanently recalibrate the gene expression patterns in cells.

In order to test this possibility, Shi and others found that lupus mice had a malfunctioning FAS protein that prevented their bone marrow MSCs from releasing pro-bone molecules that are integral for bone maintenance and deposition.

A deficiency for the FAS protein prevents bone marrow stem cells from releasing a microRNA called miR-29b.  The failure to release miR-29b causes its concentrations to increase inside the cells.  miR-29b can down-regulate an enzyme called DNA methyltransferase 1 (Dnmt1), and the buildup of miR-29b inhibits Dnmt1, which causes decreased methylation of the Notch1 promoter and activation of Notch signaling.  Methylation of the promoters of genes tends to shut down gene expression, and the lack of methylation of the Notch promoter increases Notch gene expression, activating Notch signaling.  Unfortunately, increased Notch signaling impaired the differentiation of bone marrow stem cells into bone-making cells.  Transplantation of MSCs brings FAS protein to the bone marrow stem cells by means of exosomes secreted by the MSCs.  The FAS protein in the MSC-provided exosomes reduce intracellular levels of miR-29b, which leads to higher levels of Dnmt1.  Dnmt1 methylates the Notch1 promoter, thus shutting down the expression of the Notch gene, and restoring bone-specific differentiation.

Shi and others are presently investigating if this FAS-dependent process is also at work in other autoimmune diseases.  If so, then stem cell treatments might convey similar bone-specific benefits.

MSC Transplantation Reduces Bone Loss via Epigenetic Regulation of Notch Signaling in Lupus


Mesenchymal stem cells from bone marrow, fat, and other tissues have been used in many clinical trials, experiments, and treatment regimens. While these cells are not magic bullets, they do have the ability to suppress unwanted inflammation, differentiate into bone, cartilage, tendon, smooth muscle, and fat, and can release a variety of healing molecules that help organs from hearts to kidneys heal themselves.

Mesenchymal stem cell transplantation (MSCT) is the main means by which mesenchymal stem cells are delivered to patients for therapeutic purposes. However, the precise mechanisms that underlie the success of these cells are not fully understood. In a paper by from the University Of Pennsylvania School Of Dental Medicine published in the journal Cell Metabolism, MSCT were able to re-establish the bone marrow function in MRL/lpr mice. The MRL/lpr mouse is a genetic model of a generalized autoimmune disease sharing many features and organ pathology with systemic lupus erythematosus (SLE). Such mice show bone loss and poor bone deposition, a condition known as “osteopenia.” Because mesenchymal stem cells are usually the cells in bone marrow that differentiate into osteoblasts (which make bone) a condition like osteopenia results from defective mesenchymal stem cell function.

In this paper, Shi and his coworkers and collaborators showed that the lack of the Fas protein in the mesenchymal stem cells from MRL/lpr mice prevents them from releasing a regulatory molecule called “miR-29b.” This regulatory molecule, mir-29b, is a small RNA molecule known as a microRNA. MicroRNAs regulate the expression of other genes, and the failure to release miR-29b increases the intracellular levels of miR-29b. This build-up in the levels of miR-29b causes the downregulation of an enzyme called “DNA methyltransferase 1” or Dnmt1. This is not surprising, since this is precisely what microRNAs do – they regulate genes. Dnmt1 attaches methyl groups (CH3 molecules) to the promoter or control regions of genes.

Decrease in the levels of Dnmt1 causes hypomethylation of the Notch1 promoter. When promoters are heavily methylated, genes are poorly expressed. When very methyl groups are attached to the promoters, then the gene has a greater chance of being highly expressed. Robust expression of the Notch1 genes activates Notch signaling. Increased Notch signaling leads to impaired bone production, since differentiation into bone-making cells requires mesenchymal stem cells to down-regulate Notch signaling.

When normal mesenchymal stem cells are transplanted into the bone marrow of MRL/lpr mice, they release small vesicles called exosomes that transfer the Fas protein to recipient MRL/lpr bone marrow mesenchymal stem cells. The presence of the Fas protein reduces intracellular levels of miR-29b, and this increases Dnmt1-mediated methylation of the Notch1 promoter. This decreases the expression of Notch1 and improves MRL/lpr BMMSC function.

fx1

These findings elucidate the means by which MSCT rescues MRL/lpr BMMSC function. Since MRL/lpr mice are a model system for lupus, it suggests that donor mesenchymal stem cell transplantation into lupus patients provides Fas protein to the defective, native mesenchymal stem cells, thereby regulating the miR-29b/Dnmt1/Notch epigenetic cascade that increases differentiation of mesenchymal stem cells into osteoblasts and bone deposition rates.

Bone Marrow or Umbilical Cord Stem Cells Treat Refractory Lupus-Related Kidney Disease


Autoimmune diseases are those diseases in which the patient’s own immune system attacks his or her own tissues. the treatment of such diseases requires giving patients drugs that suppress the immune system. Such drugs have potent side effects and taking such drugs long-term can also predispose patients to cancers and other types of inimical conditions.

One particular type of autoimmune disease, Systemic Lupus Erythematosis, otherwise known as SLE or just Lupus, results from an immune response against components inside our cells. The recognition of these proteins and other substances by our immune system causes massive cell damage and death. However, lupus is a very individual disease. In some patients, the disease manifests by producing butterfly-like lesions on the face.

Lupus butterfly rash (from http://emedicine.medscape.com/article/332244-overview)
Lupus butterfly rash (from http://emedicine.medscape.com/article/332244-overview)

In others, a severe arthritis in several joints results. In other lupus patients, the liver undergoes progressive degradation and scarring. Still others have severe heart problems, and others have scarring and progressive damage to the kidneys. In other patients a combination of symptoms and organs are affected. Some cases of lupus are sporadic and mild, but others are fulminant and relentless. The particular disease a person shows is completely individual.

In some lupus patients, the kidneys experience lupus nephritis (LN), which is inflammation of the tissues of the kidney. In some patients, drug treatments with corticosteroid drugs like prednisone, or other drugs like hydroxychloroquine (Plaquenil), also can help control lupus. Other drugs include powerful immune suppressants such as cyclophosphamide (Cytoxan), azathioprine (Imuran, Azasan), mycophenolate (Cellcept), leflunomide (Arava) and methotrexate (Trexall), all of which have lists of side effects that include increased risk of infection, liver damage, decreased fertility and an increased risk of cancer. However in a percentage of LN patients, drug treatments simply do not work, and these conditions are known as refractory LN.

A new clinical trial has examined the ability of mesenchymal stem cells from bone marrow or umbilical cord tissue to treat refractory LN. This Chinese study examined 81 patients with active refractory LN. The mesenchymal stem cells (MSCs) used in this study were “allogeneic,” which means that they were taken from someone other than the patient. Such treatments have been shown to successfully treat patients with other types of autoimmune diseases (see Figueroa FE, et al., Biol Res. 2012;45(3):269-77).

In this single-center clinical trial, Fei Gu and Dandan Wang and others from the Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu, China enrolled 81 Chinese patients with active and refractory LN from 2007 to 2010. These patients received by intravenous administration either allogeneic bone marrow- or umbilical cord-derived MSCs at a dose of 1 million cells per kilogram of bodyweight. All 81 patients were then monitored over the course of one year with periodic follow-up visits to evaluate kidney function and to determine if the patients were experiencing any adverse events from the stem cell treatments.

During the year-long follow-up, 77 of the 81 patients survived ( survival rate of 95%) and 49/81 patients (60.5%) achieved remission. Eleven of 49 (22.4 %) patients showed a “renal flare,” which means that their symptoms and kidney inflammation returned by the end of 12 months after having previously experienced complete remission.

Kidney function jumped during this time. The main measure of kidney function is a test called the glomerular filtration rate or GFR. This measures how well the kidney filters materials per unit time. GFR in these patients improved significantly 12 months after the stem cell treatment (mean ± SD, from 58.55 ± 19.16 to 69.51 ± 27.93 mL/min). Two other measures used to determine the severity of lupus in a patient (Systemic Lupus Erythematosus Disease Activity Index or SLEDAI score), and the activity of lupus within the kidney (British Isles Lupus Assessment Group or BILAG scores) also decreased consistently, showing that the severity of the disease decreased and the severity of the disease within the kidney also decreased after the stem cell treatment (BILAG scores – 4.48 ± 2.60 at baseline to 1.09 ± 0.83 at 12 month and the SLEDAI scores – 13.11 ± 4.20 at baseline to 5.48 ± 2.77 at 12 months).

If that is not convincing, get this: the doses of prednisone and immunosuppressive drugs required by these patients were tapered. In other words, patients were able to eventually get off their drugs sometime within this year-long period. Is that cool or what!! No transplantation-related adverse events were observed.

Thus, the authors conclude, “Allogeneic MSCT resulted in renal remission for active LN patients within 12-month visit, confirming its use as a potential therapy for refractory LN.”

Now this treatment is NOT a cure. Several patients still experienced renal flares one year after treatment, and not all the patients experienced remission. Therefore, this is not a treatment for everyone. Identifying which patients will be helped by these treatments might require microarray analyses, but the bottom line is clear – some patients are definitely helped by MSC treatments.

Granted this is a small study and it is not a controlled study – these stem cell-treated patients were not compared to anything else. However it is a very hopeful beginning. There were no adverse side effects and 60% of the patients experienced remission, and that is definitely good news

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.

An Efficient Method for Converting Fat Cells to Liver Cells


I have a friend whose wife has systemic lupus erythematosis, and her liver has taken a beating as a result of this disease. She has never had a drop of alcohol for decades and yet she has a liver that looks like the liver of a 70-year-old alcoholic. The scarring of the liver as result of repeated damage and healing has seriously compromised her liver function. She is now a candidate for a liver transplant. Wouldn’t it be nice to simply give her liver cells to heal her liver?

This dream came a little closer to becoming reality in October of this year when scientists at Stanford University developed a fast and efficient way to convert fat cells isolated from routine liposuction into liver cells. Even though these experiments used mice, the stem cells were isolated from human liposuction procedures.

This experiment did not use embryonic stem cells or induced pluripotent stem cells to generate liver cells. Instead it used adult stem cells from fat.

Fat-based stem cells

The liver builds complex molecules, filters and breaks down waste products and toxic substances that might otherwise accumulate to dangerous concentrations.

The liver, unlike other organs, has a capacity to regenerate itself to a significant extent, but the liver’s regenerative abilities cannot overcome the consequences of acute liver poisoning, or chronic damage to the liver, as a result of hepatitis, alcoholism, or drug abuse.

For example, acetaminophen (Tylenol) is a popular pain-reliever, but abusing acetaminophen can badly damage the liver. About 500 people die each year from abuse of acetaminophen, and some 60,000 emergency-room visits and more than 25,000 hospitalizations annually are due to acetaminophen abuse. Other environmental toxins, such as poisonous mushrooms, contribute more cases of liver damage.

Fortunately, the fat-to-liver protocol is readily adaptable to human patients, according to Gary Peltz, professor of anesthesia and senior author of this study. The procedure takes about nine days, which is easily fast enough to treat someone suffering from acute liver poisoning, who might die within a few weeks without a liver transplant.

Some 6,300 liver transplants are performed annually in he United States, and approximately 16,000 patients are on the waiting list for a liver. Every year more than 1,400 people die before a suitable liver can be found for them.

Even though liver transplantations save the lives of patients, the procedure is complicated, not without risks, and even when successful, is fraught with after effects. The largest problem is the immunosuppressant drugs that live patients must take in order to prevent their immune system from rejecting the transplanted liver. Acute rejection is an ongoing risk in any solid organ transplant, and improvements in immunosuppressive therapy have reduced rejection rates and improved graft survival. However, acute rejection still develops in 25% to 50% of liver transplant patients treated with immunosuppressants. Chronic rejection is somewhat less frequent and is declining and occurs in approximately 4% of adult liver transplant patients.

Peltz said, “We believe our method will be transferable to the clinic, and because the new liver tissue is derived from a person’s own cells, we do not expect that immunosuppressants will be needed.”

Peltz also noted that fat-based stem cells do not normally differentiate into liver cells. However, in 2006, a Japanese laboratory developed a technique for converting fat-based stem cells into induced liver cells (called “i-Heps” for short). This method, however, is inefficient, takes 30 days, and relies on chemical stimulation. In short, this technique would not provide enough material to regenerate a liver.

The Stanford University group built upon the Japanese work and improved it. Peltz’s group used a spherical culture and were able to convert fat-bases stem cells into i-Heps in nine days and with 37% efficiency (the Japanese group only saw a 12% rate). Since the publication of their paper, Peltz said that workers in his laboratory have increased the efficiency to 50%.

Dan Xu, a postdoctoral scholar and the lead author of this study, adapted the spherical culture methodology from early embryonic-stem-cell literature. However, instead of growing on flat surfaces in a laboratory dish, the harvested fat cells are cultured in a liquid suspension in which they form spheroids. Peltz noted that the cells were much happier when they were grown in small spheres.

Once they had enough cells, Peltz and his co-workers injected them into immune-deficient laboratory mice that accept human grafts. These mice were bioengineered in 2007 as a result of a collaboration between Peltz and Toshihiko Nishimura from the Tokyo-based Central Institute for Experimental Animals. These mice had a viral thymidine kinase gene inserted into their genomes and when treated with the drug gancyclovir, the mice experienced extensive liver damage.

After gancyclovir treatment, Peltz and his coworkers injected 5 million i-Heps into the livers of these mice, using ultrasound-guided injection procedures, which is typically used for biopsies.

Four weeks later, the mice expressed human blood proteins and 10-20 percent of the mouse livers were repopulated with human liver cells. Blood tests also showed that the mouse livers, which were greatly damaged previous to the transplantation, were processing nitrogenous wastes properly. Structurally, the mouse livers contained human cells that made human bile ducts, and expressed mature human liver cells.

Other tests established that the i-Heps made from fat-based stem cells were more liver-like than i-Heps made from induced pluripotent stem cells.

Two months are injection of the i-Heps, there was no evidence of tumor formation.

Peltz said, “To be successful, we must regenerate about half of the damaged liver’s original cell count.” With the spherical culture, Peltz is able to produce close to one billion injectable i-Heps from 1 liter of liposuction aspirate. The cell replication that occurs after injection expands that number further to over 100 billion i-Heps.

If this is possible, then this procedure could potentially replace liver transplants. Stanford University’s Office of Technology Licensing has filed a patent on the use of spherical culture for hepatocyte (liver cell) induction. Peltz’s group is optimizing this culture and injection techniques,talking to the US Food and Drug Administration, and gearing up for safety tests on large animals. Barring setbacks, the new method could be ready for clinical trials within two to three years, according the estimations by Peltz.

New Liver Drug Gets Fast Tracked by the FDA


Liver scarring (fibrosis) and cirrhosis (deposition and build up of fatty deposits in the liver) are life-threatening events. We normally associate cirrhosis in our thinking with chronic alcoholism, but there are many other conditions that can cause liver fibrosis and cirrhosis. For example, chronic systemic lupus erythematosis, which is normally just known s lupus, can wreak havoc upon the patient’s liver. Likewise Crohn’s disease, chronic hepatitis infections, or even certain genetic can cause liver disease. Once a patient’s liver scars over to a certain point. The last stop for them is either a liver transplant, or Hospice.

Until now? A biotechnology company called Galectin Therapeutics has announced that the U.S. Food and Drug Administration (FDA) has granted their new drug, GR-MD-O2 (galactoarabino-rhamnogalacturonate – say that five times fast) so-called “Fast Track designation” as an experimental treatment for non-alcoholic steatohepatitis (NASH) with hepatic fibrosis, which is also commonly known as fatty liver disease with advanced fibrosis.

GR-MD-02 is an experimental name for a complex carbohydrate drug that targets galectin-3. Galectin-3 is a cell surface protein found on liver cells and it plays a critical protein in the pathogenesis of fatty liver disease and fibrosis. Galectin proteins are central players in those diseases that involve scaring of organs such as cancer, and inflammatory and fibrotic disorders. The drug binds to galectin proteins and disrupts their function. Preclinical data have shown that GR-MD-02 can reverse fibrosis and cirrhosis in kidney, lung, and liver.

Galectin-3
Galectin-3

What is “fast track” designation? Here how this works: Fast Track is a process designed by the FDA to speed up the development and review of drugs to treat serious conditions and fill an unmet medical need. The goal is to get important new drugs to the patient earlier. Determining whether a condition is serious is a matter of judgment, but generally is based on whether the drug will have an impact on such factors as survival, day-to-day functioning, or the likelihood that the condition, if left untreated, will progress from a less severe condition to a more serious one. The kinds of conditions that have qualified for fast tracking in the past include AIDS, Alzheimer’s, heart failure and cancer. .

To qualify for fast tracking, the drug must either treat or prevent a condition with no currently available, or if there are available therapies, a fast track drug must show some advantage over available therapy. These advantages would come in the following forms:

1. Show superior effectiveness (outcomes or improved effect on serious outcomes);
2. Avoid serious side effects of an available therapy;
3. Improve the diagnosis of a serious condition (in those cases where early diagnosis results in an improved outcome);
4. Decreases clinically significant toxicity of an available therapy
5. Ability to address emerging or anticipated public health need

If a drug is fast tracked, then is will receive more frequent meetings with FDA, more frequent written correspondence from FDA, or eligibility for Accelerated Approval and Priority Review, or some combination of these.

Galectin Therapeutics is currently conducting a phase 1 clinical trial to evaluate the safety, tolerability and efficacy for single and multiple doses of GR-MD-02 over four weekly doses of GR-MD-02 treatment in patients with fatty liver disease with advanced fibrosis. In this study, Galectin will enroll eight patients in each dose escalation cohort and there will be at least three cohorts and potentially up to five cohorts, with a maximum of 40 patients at six clinical sites in the US, which each have extensive experience in clinical trials in liver disease.

“Our preclinical data has shown that GR-MD-02 has robust treatment effects in reversing fibrosis and cirrhosis. Fast Track designation enables us to expedite the compound’s development and review process, with the ultimate goal of bringing a first-in-class treatment to the millions of Americans suffering from fatty liver disease with advanced fibrosis,” said Dr. Peter Traber, president, chief executive officer and chief medical officer of Galectin Therapeutics Inc. “We are very pleased that the FDA sees the clinical value of GR-MD-02 and seriousness of fatty liver disease, and we look forward to working closely with the FDA throughout this process.”