Category Archives: Cell Medicine

Hardly anyone knew of Henrietta Lacks life story prior to 2010.

That year,Rebecca SklootsThe Immortal Life of Henrietta Lackswas released, and went on to become a New York Times best-seller. The biographical book told the story of a black woman born on a tobacco farm in Roanoke, Virginia, in 1920 who revolutionized medical research and saved the lives of millions, without ever knowing it. Now, a new film by the same name starring Oprah Winfrey aims to make her life and impact more widely known.

Who exactly was Henrietta Lacks? And why is she described as the Mother of Medicine? Here are five fascinating facts about Lacks to better understand who she was and how she changed the world forever.

The Washington Post via Getty Images

In 1951, at the age of 31,Lacks visited Baltimores Johns Hopkins Hospital, which served black patients in segregated wards during the Jim Crow era, so doctors could find out what was causing pain in her lower stomach. It turned out there was a cancerous tumor that had grown at a terrifying rate on her cervix.

At the time, cervical cancer was prevalent among women and research samples were taken from those who were diagnosed with it. Richard Telinde, a doctor at Hopkins who led a research study on patients who tested positive, hoped to grow living samples from both normal and infected cells to better understand the cancer. He worked with his colleague Dr. George Gey, the head of tissue culture research at Hopkins, who was relentlessly determined to develop the first line of immortal human cells those that could repeatedly replicate themselves outside of the body without ever dying.

Soon after her first trip to the hospital, the excruciating pain Lacks felt began to worsen as her tumor grew, so she checked herself into Hopkins for immediate treatment through surgery. The doctor who performed the surgery then removed two dime-sized pieces of tissue from Lacks body one from the infected cervix, the other from a healthy part of the organ and had them handed off to Gey. He and his staff used Lacks samples to successfully grow the first line of immortal cells. Lacks eventually died from the cancer, leaving five young children.

However, her cells lived on and soon came to be known as HeLa.

In The Immortal Life of Henrietta Lacks, Skloot writes that while Lacks gave doctors permission to perform a surgical procedure on her, she knew nothing about her cells growing in a laboratory. The hospital had called Lacks husband, David, to tell him about her death and ask if they could do an autopsy on her. Her husband initially denied the request, but visited the hospital later that day to see Lacks body and eventually agreed to sign off on the autopsy because doctors said they wanted to conduct tests that may help their children, and he believed them.

Decades after Lacks death, Rolling Stone published a riveting piece in March 1976that gave a detailed account of what happened to her cells and included comments from her husband. In the piece, he recounted his experience at the hospital after learning of her death and revealed that he had never explicitly been told by doctors or any official about what the samples had been used for:

They said it wouldnt disfigure her none, because it was all down in her womb, to begin with. He nods. They said it was the fastest growing cancer theyd ever known, and they was suppose to tell me about it, to let me know, but I never did hear.

In the same interview, Lacks eldest son,Lawrence, told the reporter: First we heard was about a month ago, a person called us on the phone and asked if wed like to take a blood test. Thats the first time we heard about it.

Helen Lane had quickly become a pseudonym for Henrietta Lacks in print, which Skloot writeswas apparently an intentional move made in an effort to disguise Lacks true identity from the public and the media. According to Skloot, one of Geys colleagues told her Gey himself had created the new name so the media wouldnt discover who Lacks really was. The Minneapolis Star was the first to publish a report on Nov. 2, 1953, that more accurately identified Lacks, only the last name was incorrect: She was recognized as Henrietta Lakes.

Upon the release of the story, journalists dug in and began requesting interviews with Gey and other doctors central to the case, but they all were reluctant to release her real name at the risk of getting into trouble, according to the book.Skloot firmly concludes that had Lacks name been released to the public from the outset, it would have changed her familys life forever.

They would have learned that Henriettas cells were still alive, that theyd been taken, bought, sold and used in research without her knowledge or theirs, she wrote.

HeLa cells have entirely revolutionized medical research. The cell line can be found in labs across the world and has been used in studies that have resulted in countless breakthroughs.

The cells were used to develop the first polio vaccine in 1952 during a time when the disease swept the nation in an outbreakthat left thousands of children paralyzed.

HeLa cells have also traveled to space to help scientists study the impact zero gravity has on human cells; been used to identify abnormalities in chromosomes; helped with research in the mapping of the human genome; and aided in studying the human papillomavirus, commonly known as HPV, which causes the cervical cancer that killed Lacks.

In 2014, chemists and engineers at Penn State University announced that in their study, HeLa cells had been implanted with technology that have potential to cure cancer if they are able to mechanically manipulate cells inside the body.

Both of Lacks daughters have died, including Deborah, who was hugely instrumental in bringing the book to life by working with Skloot and whom Oprah portrays in the film. But her legacy lives on through her three sons, who are now decades old.

And its Lacks eldest son, Lawrence, reportedly the executor of her estate, who is leading the charge for the family to receive compensation from Johns Hopkins Hospital and others. However, in a statement obtained by The Washington Post in February, the institute said it does not own the rights for the HeLa cell line and that they have not profited from the cells.Lawrence plans on continuing to pursue his mission.

Before Deborahs death in 2009, she told Skloot that even though she and her siblings lost their mother, Lacks always knew how to make her presence known.

Deborah believed Henriettas spirit lived on in her cells, controlling the life of anyone who crossed its path, Skloot wrote.Including me.

The Immortal Life of Henrietta Lacks premieres on HBO on Saturday, April 22.

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Who Was Henrietta Lacks? 5 Striking Facts About The 'Mother Of Modern Medicine' - Huffington Post

The challenge of finding a cure for AIDS may have gotten harder. Scientists have discovered another cell in the body where HIV the virus that causes AIDS hides from therapy designed to suppress it to undetectable levels in the blood.

The cells called macrophages are part of the immune system and are found throughout the body, including in the liver, lungs, bone marrow and brain. After other immune cells have done their job of destroying foreign invaders, these large white blood cells act as the cleanup crew. They surround and clean up cellular debris, foreign substances, cancer cells and anything else that is not essential to the functioning of healthy cells. In addition, they apparently can harbor HIV.

A new target

While antiretroviral drugs can drive the AIDS virus down to virtually undetectable levels, scientists know if therapy is interrupted, an HIV infection can come roaring back. That's because of a viral reservoir that until now has been thought only to inhabit immune system T-cells the cells that are attacked and destroyed by the AIDS virus. Much research is dedicated to trying to find ways to eradicate the T-cell reservoir.

This may mean researchers must find ways to eliminate HIV from macrophages, as well.

The finding was published in Nature Medicine by researchers in the Division of Infectious Diseases at the University of North Carolina School of Medicine.

Investigators demonstrated in a mouse model that in the absence of humanized T-cells, antiretroviral drugs could strongly suppress HIV in macrophages. However, when the therapy was interrupted, the virus rebounded in one-third of the mice. This, say researchers, is consistent with persistent infection in the face of drug therapy.

Researchers say their work demonstrates that any possible therapies must address macrophages in addition to T-cells to eradicate viral reservoirs. Investigators say they now have more information pointing to the complexity of the virus, and that targeting the viral reservoir in T-cells in the blood will not necessarily work with tackling HIV persistence in macrophages, which reside in tissues and are harder to observe.

Senior author Victor Garcia said its possible there are other HIV reservoirs still to be discovered.

The lead author of the study, Jenna Honeycutt, called the discovery "paradigm changing" in the way scientists must now try to eliminate persistent infection in HIV-positive individuals.

Investigators say their next step is to figure out what regulates HIV persistence in infected macrophages. They are also interested in finding HIV interventions that completely eradicate the AIDS virus from the body.

Read more here:
Second Immune Cell Found to Harbor HIV During Treatment - Voice of America

Harvard Gazette

Researchers study secrets of aging via stem cells Harvard Gazette Much of stem cell medicine is ultimately going to be 'medicine,' he said. Even here, we thought stem cells would provide mostly replacement parts. I think that's clearly changed very dramatically. Now we think of them as contributing to our ability ... Stem Cell Research Products Industry Analysis, Growth, Trend, Opportunities, Tools and Technologies 2016Medgadget (blog) all 10 news articles »

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Researchers study secrets of aging via stem cells - Harvard Gazette

PALO ALTO A Stanford research team has created a potentially powerful new way to fix damaged corneas a major source of vision problems and blindness.

Millions of new eye cells are being grown in a Palo Alto lab, enlisting one of medicines most important and promising new tools: refurbishing diseased and damaged tissue with healthy new cells.

One of the exciting possibilities of this cellular approach is that one donor cornea, which contributes a few parent cells, can generate enough cells to treat tens or hundreds of patients, said lead researcher Dr. Jeffrey Goldberg, professor and chairman of the Department of Ophthalmology at the Stanford University School of Medicine.

About 100,000 corneal transplants are done annually in the United States but they require surgery with donated corneas from cadavers. The procedure fails nearly a third of the time, and there arent enough high-quality donor corneas to go around.

Other scientists have been trying to grow full corneas from scratch, attaching a fragile film of cells to a membrane. Thats a challenging bioengineering problem.

Stanfords innovative strategy, eight years in the making, is to grow individual cells instead. The team then harvests a few mother corneal cells, called progenitor cells, donated from a cadaver.

These cells are then put into a warm broth in petri dishes, where they give birth to many new young corneal cells.

The cells are being grown at Stanfords new Laboratory for Cell and Gene Medicine, a 25,000-square-foot biological manufacturing facility on Palo Altos California Avenue.

The Stanford team enlisted a recent technological advance: magnetic nanoparticles. The particles are incredibly small, measuring only 50 nanometers in diameter. By comparison, a human hair is 75,000 nanometers in diameter.

The new young cells were magnetized with the nanoparticles, loaded into a syringe and injected into the eye.Then, using an electromagnetic force on a patch held outside of the eye, the team pulled the cells into the middle of the eye, to the back of cornea. Later, the magnetic nanoparticles fell off the cells, exited the eye and were excreted in the patients urine.

Ultimately, Goldberg said, the team hopes to mass produce off-the-shelf cells that can be easily transplanted into patients with severe damage to the cornea, the transparent outer coating of the eye that covers the iris and pupil.

In the first trial of 11 patients, a so-called Phase 1 trial, the team only studied safety.

Not only was the procedure safe, but we are seeing hints of efficacy that we are very excited about, Goldberg said. Were cautiously optimistic.

The Stanford team plans to expand the study in September to Phase 2 to measure how the vision of the patients improves.

The effort has been endorsed by the American Academy of Ophthalmology, which says it supports innovative clinical Many countries outside the United States and Europe have a shortage of donor eye tissue, leaving millions of people unable to obtain a donor cornea. If this early research is found to be safe and effective, this technique may help some patients avoid corneal transplant, said Dr. Philip R. Rizzuto, clinical spokesman for the American Academy of Ophthalmology.

If successful, the approach could also be used to replace other types of damaged eye cells, offering therapies for retinal and optic nerve diseases including glaucoma, the leading cause of irreversible blindness, he said.

The approach is part of an expanding field of lab-grown cell therapies. Sheets of healthy skin are used to treat burns, chronic skin wounds and diseases like epidermolysis bullosa, which causes incurable blistering. And bioengineered cartilage is increasingly used to treat certain knee injuries.

Stanford researchers believe that lab-grown corneal cells could become another important type of regenerative medicine.

Unlike other transplants, corneas in the Stanford teams approach dont have to be a perfect match. Rejection can be prevented with simple topical eyedrops.

Goldberg predicted that the approach could eventually replace about 80 percent of corneal transplants.

Specifically, it could repair the damaged inner layer of the cornea, called the endothelium, as seen in diseases like Fuchs dystrophy, which causes corneal damage due to swelling. It would not help in the 20 percent of transplants needed to fix the middle layer of the cornea, called the stroma.

Next month, the team will analyze its early Phase 1 data and also apply for permission from the U.S. Food and Drug Administration to begin Phase 2.

While relatively few people in the United States suffer diseases or injuries that cause devastating cornea damage, the numbers are much greater in developing nations, where infectious eye diseases remain common.

The new approach could offer a nonsurgical permanent solution in those countries, Goldberg said.

Half the world has no access to tissue, he said. I would love this to be one and done, solving patients problems for decades.

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Stanford lab grows cornea cells for transplant - The Mercury News

PEOPLE.com

The Incredible True Story of Henrietta Lacks the Most Important Woman in Modern Medicine PEOPLE.com This meant that the same sample of tissue could be tested multiple times for research, making her cell line immortal. Research using Lacks' cells helped spur numerous medical breakthroughs, include vaccines, cancer treatments and in vitro fertilization. Oprah Insists She Got Years of Therapy During Her Talk Show: 'I Came Out of It a Better Human Being'PEOPLE.com all 36 news articles »

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The Incredible True Story of Henrietta Lacks the Most Important Woman in Modern Medicine - PEOPLE.com

Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.

Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966,[1] is derived from the "hairy" appearance of the malignant B cells under a microscope.

In hairy cell leukemia, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets. Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count.[2] Leukemic cells may gather in the spleen and cause it to swell; this can have the side effect of making the person feel full even when he or she has not eaten much.

Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers of one or more kinds of normal blood cells, or after unexplained bruises or recurrent infections in an otherwise apparently healthy patient.

Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect.[3] It may result in somewhat more mild bruises than would otherwise be expected for a given platelet count or a mildly increased bleeding time for a minor cut. It is likely the result of producing slightly abnormal platelets in the overstressed bone marrow tissue.

Patients with a high tumor burden may also have somewhat reduced levels of cholesterol,[4] especially in patients with an enlarged spleen.[5] Cholesterol levels return to more normal values with successful treatment of HCL.

As with many cancers, the cause of hairy cell leukemia is unknown. Exposure to tobacco smoke, ionizing radiation, or industrial chemicals (with the possible exception of diesel) does not appear to increase the risk of developing HCL.[6] Farming and gardening appear to increase the risk of HCL in some studies.[7]

Recent studies have identified somatic BRAF V600E mutations in all patients with the classic form of hairy cell leukemia thus sequenced, but in no patients with the variant form.[8]

The U.S. Institute of Medicine (IOM) announced "sufficient evidence" of an association between exposure to herbicides and later development of chronic B-cell leukemias and lymphomas in general. The IOM report emphasized that neither animal nor human studies indicate an association of herbicides with HCL specifically. However, the IOM extrapolated data from chronic lymphocytic leukemia and non-Hodgkin lymphoma to conclude that HCL and other rare B-cell neoplasms may share this risk factor.[9] As a result of the IOM report, the U.S. Department of Veterans Affairs considers HCL an illness presumed to be a service-related disability (see Agent Orange).

Human T-lymphotropic virus 2 (HTLV-2) has been isolated in a small number of patients with the variant form of HCL.[10] In the 1980s, HTLV-2 was identified in a patient with a T-cell lymphoproliferative disease; this patient later developed hairy cell leukemia (a B cell disease), but HTLV-2 was not found in the hairy cell clones.[11] There is no evidence that HTLV-II causes any sort of hematological malignancy, including HCL.[12]

The diagnosis of HCL may be suggested by abnormal results on a complete blood count (CBC), but additional testing is necessary to confirm the diagnosis. A CBC normally shows low counts for white blood cells, red blood cells, and platelets in HCL patients. However, if large numbers of hairy cells are in the blood stream, then normal or even high lymphocyte counts may be found.

On physical exam, 8090% of patients have an enlarged spleen, which can be massive.[13] This is less likely among patients who are diagnosed at an early stage. Peripheral lymphadenopathy (enlarged lymph nodes) is uncommon (less than 5% of patients), but abdominal lymphadenopathy is a relatively common finding on computed tomography (CT) scans.[13]

The most important lab finding is the presence of hairy cells in the bloodstream.[13] Hairy cells are abnormal white blood cells with hair-like projections of cytoplasm; they can be seen by examining a blood smear or bone marrow biopsy specimen. The blood film examination is done by staining the blood cells with Wright's stain and looking at them under a microscope. Hairy cells are visible in this test in about 85% of cases.[13]

Most patients require a bone marrow biopsy for final diagnosis. The bone marrow biopsy is used both to confirm the presence of HCL and also the absence of any additional diseases, such as Splenic marginal zone lymphoma or B-cell prolymphocytic leukemia. The diagnosis can be confirmed by viewing the cells with a special stain known as TRAP (tartrate resistant acid phosphatase).

It is also possible to definitively diagnose hairy cell leukemia through flow cytometry on blood or bone marrow. The hairy cells are larger than normal and positive for CD19, CD20, CD22, CD11c, CD25, CD103, and FMC7.[14] (CD103, CD22, and CD11c are strongly expressed.)[15]

Hairy cell leukemia-variant (HCL-V), which shares some characteristics with B cell prolymphocytic leukemia (B-PLL), does not show CD25 (also called the Interleukin-2 receptor, alpha). As this is relatively new and expensive technology, its adoption by physicians is not uniform, despite the advantages of comfort, simplicity, and safety for the patient when compared to a bone marrow biopsy. The presence of additional lymphoproliferative diseases is easily checked during a flow cytometry test, where they characteristically show different results.[16]

The differential diagnoses include: several kinds of anemia, including myelophthisis and aplastic anemia,[17] and most kinds of blood neoplasms, including hypoplastic myelodysplastic syndrome, atypical chronic lymphocytic leukemia, B-cell prolymphocytic leukemia, or idiopathic myelofibrosis.[16]

When not further specified, the "classic" form is often implied. However, two variants have been described: Hairy cell leukemia-variant[18] and a Japanese variant. The non-Japanese variant is more difficult to treat than either 'classic' HCL or the Japanese variant HCL.

Hairy cell leukemia-variant, or HCL-V, is usually described as a prolymphocytic variant of hairy cell leukemia.[19] It was first formally described in 1980 by a paper from the University of Cambridge's Hayhoe lab.[20] About 10% of people with HCL have this variant form of the disease, representing about 60-75 new cases of HCL-V each year in the U.S. While classic HCL primarily affects men, HCL-V is more evenly divided between males and females.[21] While the disease can appear at any age, the median age at diagnosis is over 70.[22]

Similar to B-cell prolymphocytic leukemia ("B-PLL") in Chronic lymphocytic leukemia, HCL-V is a more aggressive disease. Historically, it has been considered less likely to be treated successfully than is classic HCL, and remissions have tended to be shorter.

However, the introduction of combination therapy with concurrent rituximab and cladribine therapy has shown excellent results in early follow-up.[23] As of 2016, this therapy is considered the first-line treatment of choice for many people with HCL-V.[24]

Many older treatment approaches, such as Interferon-alpha, the combination chemotherapy regimen "CHOP", and common alkylating agents like cyclophosphamide showed very little benefit.[21] Pentostatin and cladribine administered as monotherapy (without concurrent rituximab) provide some benefit to many people with HCL-V, but typically induce shorter remission periods and lower response rates than when they are used in classic HCL. More than half of people respond partially to splenectomy.[21]

In terms of B-cell development, the prolymphocytes are less developed than are lymphocytes or plasma cells, but are still more mature than their lymphoblastic precursors.

HCL-V differs from classic HCL principally in the following respects:

Low levels of CD25, a part of the receptor for a key immunoregulating hormone, may explain why HCL-V cases are generally much more resistant to treatment by immune system hormones.[19]

HCL-V, which usually features a high proportion of hairy cells without a functional p53 tumor suppressor gene, is somewhat more likely to transform into a higher-grade malignancy. A typical transformation rate of 5%-6% has been postulated in the U.K., similar to the Richter's transformation rate for SLVL and CLL.[21][27] Among HCL-V patients, the most aggressive cases normally have the least amount of p53 gene activity.[28] Hairy cells without the p53 gene tend, over time, to displace the less aggressive p53(+) hairy cells.

There is some evidence suggesting that a rearrangement of the immunoglobulin gene VH4-34, which is found in about 40% of HCL-V patients and 10% of classic HCL patients, may be a more important poor prognostic factor than variant status, with HCL-V patients without the VH4-34 rearrangement responding about as well as classic HCL patients.[29]

Hairy cell leukemia-Japanese variant or HCL-J. There is also a Japanese variant, which is more easily treated.

Treatment with cladribine has been reported.[30]

Pancytopenia in HCL is caused primarily by marrow failure and splenomegaly. Bone marrow failure is caused by the accumulation of hairy cells and reticulin fibrosis in the bone marrow, as well as by the detrimental effects of dysregulated cytokine production.[13] Splenomegaly reduces blood counts through sequestration, marginalization, and destruction of healthy blood cells inside the spleen.[13]

Hairy cells are nearly mature B cells, which are activated clonal cells with signs of VH gene differentiation.[16] They may be related to pre-plasma marginal zone B cells[13] or memory cells.

Cytokine production is disturbed in HCL. Hairy cells produce and thrive on TNF-alpha.[13] This cytokine also suppresses normal production of healthy blood cells in the bone marrow.[13]

Unlike healthy B cells, hairy cells express and secrete an immune system protein called Interleukin-2 receptor (IL-2R).[13] In HCL-V, only part of this receptor is expressed.[13] As a result, disease status can be monitored by measuring changes in the amount of IL-2R in the blood serum.[13] The level increases as hairy cells proliferate, and decreases when they are killed. Although uncommonly used in North America and northern Europe, this test correlates better with disease status and predicts relapse more accurately than any other test.

Hairy cells respond to normal production of some cytokines by T cells with increased growth. Treatment with Interferon-alpha suppresses the production of this pro-growth cytokine from T cells.[13] A low level of T cells, which is commonly seen after treatment with cladribine or pentostatin, and the consequent reduction of these cytokines, is also associated with reduced levels of hairy cells.

In June 2011, E Tiacci et al[31][32] discovered that 100% of hairy-cell leukaemia samples analysed had the oncogenic BRAF mutation V600E, and proposed that this is the disease's driver mutation. Until this point, only a few genomic imbalances had been found in the hairy cells, such as trisomy 5 had been found.[13] The expression of genes is also dysregulated in a complex and specific pattern. The cells underexpress 3p24, 3p21, 3q13.3-q22, 4p16, 11q23, 14q22-q24, 15q21-q22, 15q24-q25, and 17q22-q24 and overexpress 13q31 and Xq13.3-q21.[33] It has not yet been demonstrated that any of these changes have any practical significance to the patient.

Several treatments are available, and successful control of the disease is common.

Not everyone needs treatment. Treatment is usually given when the symptoms of the disease interfere with the patient's everyday life, or when white blood cell or platelet counts decline to dangerously low levels, such as an absolute neutrophil count below one thousand cells per microliter (1.0 K/uL). Not all patients need treatment immediately upon diagnosis, and about 10% of patients will never need treatment.

Treatment delays are less important than in solid tumors. Unlike most cancers, treatment success does not depend on treating the disease at an early stage. Because delays do not affect treatment success, there are no standards for how quickly a patient should receive treatment. However, waiting too long can cause its own problems, such as an infection that might have been avoided by proper treatment to restore immune system function. Also, having a higher number of hairy cells at the time of treatment can make certain side effects somewhat worse, as some side effects are primarily caused by the body's natural response to the dying hairy cells. This can result in the hospitalization of a patient whose treatment would otherwise be carried out entirely at the hematologist's office.

Single-drug treatment is typical. Unlike most cancers, only one drug is normally given to a patient at a time. While monotherapy is normal, combination therapytypically using one first-line therapy and one second-line therapyis being studied in current clinical trials and is used more frequently for refractory cases. Combining rituximab with cladribine or pentostatin may or may not produce any practical benefit to the patient.[34] Combination therapy is almost never used with a new patient. Because the success rates with purine analog monotherapy are already so high, the additional benefit from immediate treatment with a second drug in a treatment-nave patient is assumed to be very low. For example, one round of either cladribine or pentostatin gives the median first-time patient a decade-long remission; the addition of rituximab, which gives the median patient only three or four years, might provide no additional value for this easily treated patient. In a more difficult case, however, the benefit from the first drug may be substantially reduced and therefore a combination may provide some benefit.

Cladribine (2CDA) and pentostatin (DCF) are the two most common first-line therapies. They both belong to a class of medications called purine analogs, which have mild side effects compared to traditional chemotherapy regimens.

Cladribine can be administered by injection under the skin, by infusion over a couple of hours into a vein, or by a pump worn by the patient that provides a slow drip into a vein, 24 hours a day for 7 days. Most patients receive cladribine by IV infusion once a day for five to seven days, but more patients are being given the option of taking this drug once a week for six weeks. The different dosing schedules used with cladribine are approximately equally effective and equally safe.[35] Relatively few patients have significant side effects other than fatigue and a high fever caused by the cancer cells dying, although complications like infection and acute kidney failure have been seen.

Pentostatin is chemically similar to cladribine, and has a similar success rate and side effect profile, but it is always given over a much longer period of time, usually one dose by IV infusion every two weeks for three to six months.

During the weeks following treatment the patient's immune system is severely weakened, but their bone marrow will begin to produce normal blood cells again. Treatment often results in long-term remission. About 85% of patients achieve a complete response from treatment with either cladribine or pentostatin, and another 10% receive some benefit from these drugs, although there is no permanent cure for this disease. If the cancer cells return, the treatment may be repeated and should again result in remission, although the odds of success decline with repeated treatment.[36] Remission lengths vary significantly, from one year to more than twenty years. The median patient can expect a treatment-free interval of about ten years.

It does not seem to matter which drug a patient receives. A patient who is not successfully treated with one of these two drugs has a reduced chance of being successfully treated with the other. However, there are other options.

If a patient is resistant to either cladribine or pentostatin, then second-line therapy is pursued.

Monoclonal antibodies The most common treatment for cladribine-resistant disease is infusing monoclonal antibodies that destroy cancerous B cells. Rituximab is by far the most commonly used. Most patients receive one IV infusion over several hours each week for four to eight weeks. A 2003 publication found two partial and ten complete responses out of 15 patients with relapsed disease, for a total of 80% responding.[37] The median patient (including non-responders) did not require further treatment for more than three years. This eight-dose study had a higher response rate than a four-dose study at Scripps, which achieved only 25% response rate.[38] Rituximab has successfully induced a complete response in Hairy Cell-Variant.[39]

Rituximab's major side effect is serum sickness, commonly described as an "allergic reaction", which can be severe, especially on the first infusion. Serum sickness is primarily caused by the antibodies clumping during infusion and triggering the complement cascade. Although most patients find that side effects are adequately controlled by anti-allergy drugs, some severe, and even fatal, reactions have occurred. Consequently, the first dose is always given in a hospital setting, although subsequent infusions may be given in a physician's office. Remissions are usually shorter than with the preferred first-line drugs, but hematologic remissions of several years' duration are not uncommon.

Other B cell-destroying monoclonal antibodies such as Alemtuzumab, Ibritumomab tiuxetan and I-131 Tositumomab may be considered for refractory cases.

Interferon-alpha Interferon-alpha is an immune system hormone that is very helpful to a relatively small number of patients, and somewhat helpful to most patients. In about 65% of patients,[40] the drug helps stabilize the disease or produce a slow, minor improvement for a partial response.[41]

The typical dosing schedule injects at least 3 million units of Interferon-alpha (not pegylated versions) three times a week, although the original protocol began with six months of daily injections.

Some patients tolerate IFN-alpha very well after the first couple of weeks, while others find that its characteristic flu-like symptoms persist. About 10% of patients develop a level of depression. It is possible that, by maintaining a steadier level of the hormone in the body, that daily injections might cause fewer side effects in selected patients. Drinking at least two liters of water each day, while avoiding caffeine and alcohol, can reduce many of the side effects.

A drop in blood counts is usually seen during the first one to two months of treatment. Most patients find that their blood counts get worse for a few weeks immediately after starting treatment, although some patients find their blood counts begin to improve within just two weeks.[42]

It typically takes six months to figure out whether this therapy is useful. Common criteria for treatment success include:

If it is well tolerated, patients usually take the hormone for 12 to 18 months. An attempt may be made then to end the treatment, but most patients discover that they need to continue taking the drug for it to be successful. These patients often continue taking this drug indefinitely, until either the disease becomes resistant to this hormone, or the body produces an immune system response that limits the drug's ability to function. A few patients are able to achieve a sustained clinical remission after taking this drug for six months to one year. This may be more likely when IFN-alpha has been initiated shortly after another therapy. Interferon-alpha is considered the drug of choice for pregnant women with active HCL, although it carries some risks, such as the potential for decreased blood flow to the placenta.

Interferon-alpha works by sensitizing the hairy cells to the killing effect of the immune system hormone TNF-alpha, whose production it promotes.[43] IFN-alpha works best on classic hairy cells that are not protectively adhered to vitronectin or fibronectin, which suggests that patients who encounter less fibrous tissue in their bone marrow biopsies may be more likely to respond to Interferon-alpha therapy. It also explains why non-adhered hairy cells, such as those in the bloodstream, disappear during IFN-alpha treatment well before reductions are seen in adhered hairy cells, such as those in the bone marrow and spleen.[43]

Splenectomy can produce long-term remissions in patients whose spleens seem to be heavily involved, but its success rate is noticeably lower than cladribine or pentostatin. Splenectomies are also performed for patients whose persistently enlarged spleens cause significant discomfort or in patients whose persistently low platelet counts suggest Idiopathic thrombocytopenic purpura.

Bone marrow transplants are usually shunned in this highly treatable disease because of the inherent risks in the procedure. They may be considered for refractory cases in younger, otherwise healthy individuals. "Mini-transplants" are possible.

Patients with anemia or thrombocytopenia may also receive red blood cells and platelets through blood transfusions. Blood transfusions are always irradiated to remove white blood cells and thereby reduce the risk of graft-versus-host disease. Patients may also receive a hormone to stimulate production of red blood cells. These treatments may be medically necessary, but do not kill the hairy cells.

Patients with low neutrophil counts may be given filgrastim or a similar hormone to stimulate production of white blood cells. However, a 1999 study indicates that routine administration of this expensive injected drug has no practical value for HCL patients after cladribine administration.[44] In this study, patients who received filgrastim were just as likely to experience a high fever and to be admitted to the hospital as those who did not, even though the drug artificially inflated their white blood cell counts. This study leaves open the possibility that filgrastim may still be appropriate for patients who have symptoms of infection, or at times other than shortly after cladribine treatment.

Although hairy cells are technically long-lived, instead of rapidly dividing, some late-stage patients are treated with broad-spectrum chemotherapy agents such as methotrexate that are effective at killing rapidly dividing cells. This is not typically attempted unless all other options have been exhausted and it is typically unsuccessful.

More than 95% of new patients are treated well or at least adequately by cladribine or pentostatin.[45] A majority of new patients can expect a disease-free remission time span of about ten years, or sometimes much longer after taking one of these drugs just once. If re-treatment is necessary in the future, the drugs are normally effective again, although the average length of remission is somewhat shorter in subsequent treatments.

As with B-cell chronic lymphocytic leukemia, mutations in the IGHV on hairy cells are associated with better responses to initial treatments and with prolonged survival.[46]

How soon after treatment a patient feels "normal" again depends on several factors, including:

With appropriate treatment, the overall projected lifespan for patients is normal or near-normal. In all patients, the first two years after diagnosis have the highest risk for fatal outcome; generally, surviving five years predicts good control of the disease. After five years' clinical remission, patients in the United states with normal blood counts can often qualify for private life insurance with some US companies.[47]

Accurately measuring survival for patients with the variant form of the disease (HCL-V) is complicated by the relatively high median age (70 years old) at diagnosis. However, HCL-V patients routinely survive for more than 10 years, and younger patients can likely expect a long life.

Worldwide, approximately 300 HCL patients per year are expected to die.[48] Some of these patients were diagnosed with HCL due to a serious illness that prevented them from receiving initial treatment in time; many others died after living a normal lifespan and experiencing years of good control of the disease. Perhaps as many as five out of six HCL patients die from some other cause.[original research?]

Despite decade-long remissions and years of living very normal lives after treatment, hairy cell leukemia is officially considered an incurable disease. While survivors of solid tumors are commonly declared to be permanently cured after two, three, or five years, people who have hairy cell leukemia are never considered 'cured'. Relapses of HCL have happened even after more than twenty years of continuous remission. Patients will require lifelong monitoring and should be aware that the disease can recur even after decades of good health.

People in remission need regular follow-up examinations after their treatment is over. Most physicians insist on seeing patients at least once a year for the rest of the patient's life, and getting blood counts about twice a year. Regular follow-up care ensures that patients are carefully monitored, any changes in health are discussed, and new or recurrent cancer can be detected and treated as soon as possible. Between regularly scheduled appointments, people who have hairy cell leukemia should report any health problems, especially viral or bacterial infections, as soon as they appear.

HCL patients are also at a slightly higher than average risk for developing a second kind of cancer, such as colon cancer or lung cancer, at some point during their lives (including before their HCL diagnosis). This appears to relate best to the number of hairy cells, and not to different forms of treatment.[49] On average, patients might reasonably expect to have as much as double the risk of developing another cancer, with a peak about two years after HCL diagnosis and falling steadily after that, assuming that the HCL was successfully treated. Aggressive surveillance and prevention efforts are generally warranted, although the lifetime odds of developing a second cancer after HCL diagnosis are still less than 50%.

There is also a higher risk of developing an autoimmune disease.[13] Autoimmune diseases may also go into remission after treatment of HCL.[13]

Because the cause is unknown, no effective preventive measures can be taken.

Because the disease is rare, routine screening is not cost-effective.

This disease is rare, with fewer than 1 in 10,000 people being diagnosed with HCL during their lives. Men are four to five times more likely to develop hairy cell leukemia than women.[50] In the United States, the annual incidence is approximately 3 cases per 1,000,000 men each year, and 0.6 cases per 1,000,000 women each year.[13]

Most patients are white males over the age of 50,[13] although it has been diagnosed in at least one teenager.[51] It is less common in people of African and Asian descent compared to people of European descent.

It does not appear to be hereditary, although occasional familial cases that suggest a predisposition have been reported,[52] usually showing a common Human Leukocyte Antigen (HLA) type.[13]

The Hairy Cell Leukemia Consortium was founded in 2008 to address researchers' concerns about the long-term future of research on the disease.[53] Partly because existing treatments are so successful, the field has attracted very few new researchers.

In 2013 the Hairy Cell Leukemia Foundation was created when the Hairy Cell Leukemia Consortium and the Hairy Cell Leukemia Research Foundation joined together. The HCLF is dedicated to improving outcomes for patients by advancing research into the causes and treatment of hairy cell leukemia, as well as by providing educational resources and comfort to all those affected by hairy cell leukemia.[54]

Three immunotoxin drugs have been studied in patients at the NIHNational Cancer Institute in the U.S.: BL22,[55]HA22[56] and LMB-2.[57] All of these protein-based drugs combine part of an anti-B cell antibody with a bacterial toxin to kill the cells on internalization. BL22 and HA22 attack a common protein called CD22, which is present on hairy cells and healthy B cells. LMB-2 attacks a protein called CD25, which is not present in HCL-variant, so LMB-2 is only useful for patients with HCL-classic or the Japanese variant. HA-22, now renamed moxetumab pasudotox, is being studied in patients with relapsed hairy cell leukemia at the National Cancer Institute in Bethesda, Maryland, MD Anderson Cancer Center in Houston, Texas, and Ohio State University in Columbus, Ohio. Other sites for the study are expected to start accepting patients in late 2014, including The Royal Marsden Hospital in London, England.[58]

Other clinical trials[59] are studying the effectiveness of cladribine followed by rituximab in eliminating residual hairy cells that remain after treatment by cladribine or pentostatin. It is not currently known if the elimination of such residual cells will result in more durable remissions.

BRAF mutation has been frequently detected in HCL (Tiacci et al. NEJM 2011) and some patients may respond to Vemurafenib

The major remaining research questions are identifying the cause of HCL and determining what prevents hairy cells from maturing normally.[60]

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Hairy cell leukemia - Wikipedia

Newswise PHILADELPHIA Genetic, stem cell, and reproductive technologies that have the capability to fundamentally change our cells is challenging what is means to be human. Correcting underlying mutations to cure human genetic disorders; reprogramming skin cells to other cell types to one day inject back into a person, or manipulating the genes of a sperm cell or egg to eliminate a sex-linked mutation are all current examples of these techniques that spur social, ethical, and moral questions. Leading biologists and bioethicists from the Institute for Regenerative Medicine at the University of Pennsylvania, and other institutions, will come together to discuss these topics in a day-long symposium entitled, Managing Cell and Human Identity. The IRM is led by Kenneth Zaret, PhD, a professor of Cell and Developmental Biology at the Perelman School of Medicine . A Perspective in Science magazine published today with the same title considers how our perceptions about human identity may help us decide how and when to use these technologies.

WHERE:

Biomedical Research Building, Perelman School of Medicine, 421 Curie Boulevard, Philadelphia PA, 19104. See here for directions and map. Event is free. See here for more details and to register.

WHEN:

Wednesday, April, 26 8:30 9:00 Registration and Breakfast

SCHEDULE:

8:30-9:00 AM Registration and Breakfast

9:00 AM Introductory Remarks

Dawn Bonnell, Ph.D., Vice Provost for Research

9:15-9:45 AM Controlling Genes and Cells: The present and future of regeneration technologies Ken Zaret, Ph.D., University of Pennsylvania Joseph Leidy Professor Director, Institute for Regenerative Medicine

9:45-10:30 AM Our Bodies, Our Selves: Theologies and Ethics for Unstable Embodiment

Laurie Zoloth, Ph.D., Northwestern University

President of Faculty Senate Director of Graduate Studies in the Department of Religious Studies

10:30-10:45AM Civic Engagement within the IRM: Lessons learned from thecommunity

Jamie Shuda, Ed.D., Director of IRM Life Science Outreach

10:45-11 AM Coffee Break

11-11:45 AM Why Do We Want to Be Human?

Jonathan Moreno, Ph.D., University of Pennsylvania

David and Lyn Silfen University Professor

11:45-12:30PM Discussion Panel

12:30-1:30 PM Lunch

1:30-2:15 PM More Than Your Genes

Reed Pyeritz, M.D., Ph.D., University of Pennsylvania William Smilow Professor of Medicine

2:15-3:00 PM Evolving Attitudes toward Heritable Genomic Modification

Warren P. Knowles Professor of Law and Bioethics

3:00-3:15 PM Coffee Break

3:15-4:00 PM How Much Longer Will We Be Human?

John Gearhart, Ph.D., University of Pennsylvania

James W. Effron University Professor

4:00-4:45 PM Discussion Panel

4:45-6:00 PM Reception

###

Penn Medicineis one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of theRaymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and theUniversity of Pennsylvania Health System, which together form a $5.3 billion enterprise.

The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 18 years, according toU.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $373 million awarded in the 2015 fiscal year.

The University of Pennsylvania Health System's patient care facilities include: The Hospital of the University of Pennsylvania and Penn Presbyterian Medical Center -- which are recognized as one of the nation's top "Honor Roll" hospitals byU.S. News & World Report-- Chester County Hospital; Lancaster General Health; Penn Wissahickon Hospice; and Pennsylvania Hospital -- the nation's first hospital, founded in 1751. Additional affiliated inpatient care facilities and services throughout the Philadelphia region include Chestnut Hill Hospital and Good Shepherd Penn Partners, a partnership between Good Shepherd Rehabilitation Network and Penn Medicine.

Penn Medicine is committed to improving lives and health through a variety of community-based programs and activities. In fiscal year 2015, Penn Medicine provided $253.3 million to benefit our community.

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Managing Cell and Human Identity - Newswise (press release)

by Kathleen Raven April 13, 2017

Jason Thomson, a core lab manager at the Yale Stem Cell Center, rebounded after large pharmaceutical companies retrenched in Connecticut. Photo credit: Robert Lisak

Six years ago, Jason Thomson learned that his 13-year position in research at Pfizer would come to an end. He was among 1,100 employees laid off at the companys drug development laboratory in Groton. He feared that his career was in jeopardy. He didnt want to move his family and worried he wouldnt be able to land a comparable job in Connecticut.

But things worked out much better than he expected. I was fortunate, says Thomson, a resident of Colchester. I was out of work for just over six months. Today, hes a lab manager at the Yale Stem Cell Center in New Haven. He plays a key role at the center, overseeing the preparation of stem cells that other researchers use to pursue their studies.

Thomsons personal journey illustrates an economic shift in Connecticut. Over the past decade, several large pharmaceutical companies have either closed their doors here or cut hundreds of jobs from their local payrolls. These moves pose a threat to the state economy. For Connecticut to thrive in the future, say state political, academic and business leaders, more jobs are needed in groundbreaking biomedical research and a home-grown biotech industry.

The 10-year-old Yale Stem Cell Center, which is within Yale School of Medicine, is an example of how this can be done. It has already created more than 200 jobs; involves more than 450 Yale faculty, post-docs and students; has produced more than 350 patent applications; and has three therapies currently being tested in clinical trials. And, because this type of research typically takes many years to have maximum impact, its likely that the best is yet to come.

So far, three clinical trials are testing drugs based on scientific advances produced by Stem Cell Center researchers. They include using cell-based tissue engineering to cure congenital heart defects, and using skeletal stem cells to treat stroke and spinal cord injuries.

Here's an infographic explaining how the Yale Stem Cell Center contributes to society.

This is about faculty members and researchers making breakthrough discoveries and passing them along to business experts to take to the market.

Yale School of Medicine plays a critical role in fostering a fast-growing bioscience industry in the New Haven area. Already, upwards of 40 biotech and medical device companies employ more than 5,000 people in greater New Haven. This is about faculty members and researchers making breakthrough discoveries and passing them along to business experts to take to the market, says Susan Froshauer, president of Connecticut United for Research Excellence (CURE), the bioscience industrys advocacy group.

At Pfizer, Thomsons job was to determine the safety profile of drugs using embryonic stem cells from mice. The New York native, who studied animal science at Cornell University, loved the company and his job, but he wasnt surprised when the bad news came. He had seen evidence that a retrenchment in the pharmaceutical industry was underway. For instance, just a few years earlier, Bayer Healthcare began shutting down its West Haven facility, which displaced about 1,000 workers. (The sprawling facility is now Yale Universitys West Campus.)

When Thomson received the layoff notice, leaving Connecticut and moving to another state wasnt an attractive option. He didnt want to disrupt his wifes career as a tenured high school teacher, nor the lives of his two young daughters.

He recalled hearing about efforts in the state to foster its strengths in biosciencein part by funding university research. Thomson began monitoring university websites. After a few nervous months, he got his big break. The Yale Stem Cell Center posted what he considered a dream job. Thomson appliedand got it.

Hes now a respected leader and colleague at the center. Caihong Qiu, Ph.D., who is the technical director of the Centers two core science labs, says researchers there admire Thomson for his deep scientific knowledge and helpful manner. Jason is the face of the core. He is very thorough and dedicated, Qiu says.

At the center, Thomson grows stem cells so scientists can conduct experiments to better understand the underlying cause of diseases, or to learn how to build new human organs. He provides feedback on study designs, orders lab supplies, and oversees the nitrogen tanks and other machinery that keep 10 years worth of cells frozen. He calls the core labs the special forces unit within the center. No matter how difficult the task is, they get it done.

Thomson loves working with stem cells because they contain clues to many unanswered questions surrounding how humans grow and develop. The long lab hours and a two-hour round-trip daily commute from his home in Colchester dont dampen his enthusiasm. Says Thompson: You have to love what you do for a living, and I do.

This article was submitted by Stephen Hamm on April 12, 2017.

Originally posted here:
How Medical Research Is Boosting Connecticut's Economy - Yale News

James E. Rothman, newly appointed as a Sterling Professor of Cell Biology, is one of the world's most distinguished biochemists and cell biologists. For his work on how molecular messages are transmitted inside and outside of human cells, he was awarded a Nobel Prize in 2013.

A Sterling Professorship is one of the universitys highest faculty honors.

Rothman helped reveal the mechanism that allows cellular compartments called vesicles to transmit information both in the interior of the cell and to the surrounding environment. The fusion of vesicles and cellular membranes, a process called exocytosis, is basic to life and occurs in organisms as diverse as yeast and humans. Exocytosis underlies physiological functions ranging from the secretion of insulin to the regulation of the brain neurotransmitters responsible for movement, perception, memory, and mood.

Rothmans current research concerns the biophysics of membrane fusion and its regulation in exocytosis; the dynamics of the Golgi apparatus at super-resolution; and the use of bio-inspired design in nanotechnology.

After graduating from Yale College with a degree in physics, Rothman earned a Ph.D. in biological chemistry from Harvard Medical School. He conducted postdoctoral research at the Massachusetts Institute of Technology before moving to the Stanford School of Medicine as an assistant professor. He continued his research at Princeton University, where he became the founding chair of the Department of Cellular Biochemistry and Biophysics at Memorial Sloan-Kettering Cancer Center and vice chair of the Sloan-Kettering Institute. Prior to coming to Yale in 2008, Rothman served on the faculty of Columbia Universitys College of Physicians and Surgeons, where he was a professor in the Department of Physiology and Biophysics, the Clyde and Helen Wu Professor of Chemical Biology, and director of the Columbia Genome Center.

Rothman serves as chair of the Yale School of Medicines Department of Cell Biology and as director of the Nanobiology Institute on Yales West Campus.

He has received numerous awards and honors in recognition of his work on vesicle trafficking and membrane fusion, including the King Faisal International Prize for Science, the Gairdner Foundation International Award, the Lounsbery Award of the National Academy of Sciences, the Heineken Foundation Prize of the Netherlands Academy of Sciences, the Louisa Gross Horwitz Prize of Columbia University, the Lasker Basic Science Award, the Kavli Prize in Neuroscience, the Massry Prize, and the E.B. Wilson Medal. He is a member of the National Academy of Sciences and its Institute of Medicine, and is a fellow of the American Academy of Arts and Sciences.

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James Rothman appointed Sterling Professor of Cell Biology - Yale News

Two of the hottest fields in biopharma got another injection of cash this week, with a combined $72 million in Series A financing.

That includes $32 million raised by Frequency Therapeutics to further its novel regenerative medicine approach, and a separate $40 million round for Cirius Therapeutics take on liver fibrosis and NASH.

Headquartered in Woburn, Massachusetts,Frequency Therapeutics was founded in 2015 with a mission to kickstart one of the bodys natural healing mechanisms. Its$32 million Series A financing round was led by CoBro Ventures, with support from Morningside Ventures, Emigrant Capital, Korean Investment Partnership, Alexandria Real Estate Equities,and others.

Frequency is built around its so-called Progenitor Cell Activation (PCA) platform developed by Robert Langer and Jeffrey Karp from MIT and Harvard Medical School. Progenitor cells are slightly more specialized than stem cells. And while they typically lie dormant after fetal development, they can be activated to regenerate damaged tissues similar to the way stems cells do.

Theyre already in the right place and trained to do the right job, explained Frequencycofounder and CSO Chris Loose, in an email forwarded by a company representative.

While the PCA platform could theoretically be applied to many fields, such as skin disorders, muscle regeneration, and gastrointestinal diseases, the initial R&D focus will bechronic hearing loss. This often occurs with the gradual loss of key cells in the inner ear, called sensory hair cells.

Frequencys small molecule therapy would activate the progenitor cells waiting in the wings, helping to replace the lost cells and loss of function for the remainder of the patients life.

Once a new hair cell is regenerated, we expect it to be long-lasting, Loose explained. The hair cells you are born with are the ones you die with, so a hair cell can survive and function for over 100 years in some people.

Also on Tuesday,Cirius Therapeutics (previously known as Octeta Therapeutics) publicized a $40 million Series A round. The financing was led by Frazier Healthcare Partners and Novo A/S.

The money is destined to fund the companys ongoingEMMINENCE trial, a Phase 2b study of its second-generation insulin sensitizer, MSDC-0602K, for the treatment of non-alcoholic steatohepatitis (NASH) and liver fibrosis.

It speaks to the novel approach Cirius is taking to control the silent epidemic of NASH, which often strikes alongside obesity, metabolic syndrome, and type 2 diabetes.

In a company statement, newly-announced CEO Bob Balteraexplainedthe connection.

A great deal of experimental data, including results from a Phase 2 trial in patients with Type 2 diabetes, has been generated demonstrating that these next-generation insulin sensitizers act in a novel way to positively impact the underlying metabolic parameters that drive NASH,Baltera said.

The challenge for the company is ensuring the safety of its candidate,MSDC-0602K. While promising, existing insulin sensitizers come with an array of problematic side effects and NASH is a high-risk patient population.

On the other hand, there are no disease-modifying therapies on the market, so a little benefit will go a long way.

Echoing others in the field, one of the lead investors noted that a combination approach to NASH will likely work best.

At Frazier, we believe the future of NASH therapies will be a multi-drug approach, with a need for therapies that address the underlying metabolic drivers of disease, as well as resultant fibrosis and inflammation, said Dan Estes of Frzaier Healthcare. We see a distinct opportunity for MSDC-0602K to become a cornerstone therapy in NASH, both as monotherapy but ultimately as part of combination approaches.

Photo: abluecup, Getty Images

Excerpt from:
Two new Series A rounds inject $72M into regenerative medicine and NASH - MedCity News