GPC Biotech Presents Preliminary Clinical Data On Anticancer Monoclonal Antibody 1D09C3 At ASH

GPC Biotech AG (Frankfurt Stock Exchange: GPC;
TecDAX index; Nasdaq: GPCB) today announced the presentation of preliminary
clinical data on its anticancer monoclonal antibody 1D09C3 at the 48th
Annual Meeting of the American Society of Hematology (ASH) in Orlando,
Florida. 1D09C3 is currently in a Phase 1 clinical program that is
evaluating the antibody in patients with relapsed or refractory B-cell
lymphomas, who have failed prior standard therapy. The objectives of the
Phase 1 program are to determine the maximum tolerated dose and to
establish a recommended dose for a Phase 2 efficacy trial.



The poster entitled, "Two Phase 1 Open-Label Studies of the Fully Human
IgG4 Monoclonal Antibody 1D09C3 in Patients with Relapsed and/or Refractory
B- Cell Lymphoproliferative Neoplasias on a Weekly and Bi-Weekly Dosing
Scheme," (Abstract #2730) presented initial results from the ongoing Phase
1 clinical program. These preliminary data from 25 patients suggest that
1D09C3 is well tolerated in this heavily pre-treated patient population. A
maximum tolerated dose had not yet been reached. Hints of antitumor
activity were observed in two patients.



"We are pleased with the initial clinical data from our antibody
program," said Marcel Rozencweig, M.D., Senior Vice President, Drug
Development and Chief Medical Officer. "Importantly, 1D09C3 seems to be
well tolerated by this heavily pre-treated patient population. The early
signs of anti-tumor activity are encouraging at these low doses. We expect
to see the final results from our Phase 1 clinical program in mid 2007.
Should the data continue to be promising, we anticipate moving into Phase 2
testing thereafter."



Dr. Rozencweig continued: "While good progress has been made in recent
years in treating lymphoid cancers with antibodies, there remains a major
need for additional therapies to treat patients who have relapsed or become
resistant to currently available treatments. 1D09C3 has key attributes
differentiating it from marketed therapies; thus, it could hold the
potential to become an important new therapy for treating lymphomas and
leukemias."



New preclinical data under the title "Interferon-Gamma Enhances the
Anti-Myeloma Activity of the Fully Human Anti-HLA-DR Monoclonal Antibody
1D09C3" (Abstract #656) will also be presented. The findings suggest that
interferon-gamma induces up-regulation of HLA-DR, the target of 1D09C3,
resulting in a potent enhancement of the in vivo anti-myeloma activity of
1D09C3.



About 1D09C3



1D09C3 is an anti-MHC (major histocompatibility complex) class II
monoclonal antibody. The antibody was isolated in collaboration with
MorphoSys from its HuCAL(R) library of human antibodies. 1D09C3 binds to
MHC class II molecules on the cell surface and selectively kills activated,
proliferating tumor cells, which include B-cell and T-cell lymphomas. In
2005, it was estimated that more than 56,000 people in the U.S. and about
70,000 people in the European Union were diagnosed with non-Hodgkin's
lymphoma, the most common form of lymphoma. In preclinical studies 1D09C3
has been shown to induce programmed cell death and does not require a
functioning immune system for its cell-killing effect. A Phase 1 clinical
program evaluating 1D09C3 in patients with relapsed or refractory B-cell
lymphomas, such as Hodgkin's and non- Hodgkin's lymphomas and chronic
lymphocytic leukemia (CLL), who have failed prior standard therapy, is
currently underway at major cancer centers in Europe. 1D09C3 has been
granted orphan medicinal product designation in the European Union for the
treatment of Hodgkin's lymphoma, chronic lymphocytic leukemia and multiple
myeloma. Additional information on 1D09C3 can be found in the Anticancer
Programs section of the Company's Web site at gpc-biotech.
















About GPC Biotech



GPC Biotech AG is a publicly traded biopharmaceutical company focused
on discovering, developing and commercializing new anticancer drugs. GPC
Biotech's lead product candidate -- satraplatin -- is an oral
platinum-based compound that has shown highly statistically significant
results for progression-free survival in a Phase 3 registrational trial as
a second-line chemotherapy treatment in hormone-refractory prostate cancer.
The U.S. FDA has granted fast track designation to satraplatin for this
indication, and the rolling NDA submission process for this compound is
underway. GPC Biotech in-licensed satraplatin from Spectrum
Pharmaceuticals, Inc. in 2002. GPC Biotech is also developing a monoclonal
antibody with a novel mechanism-of-action against a variety of lymphoid
tumors, currently in Phase 1 clinical development, and has ongoing drug
development and discovery programs that leverage its expertise in kinase
inhibitors. GPC Biotech AG is headquartered in Martinsried/Munich
(Germany), and its wholly owned U.S. subsidiary has sites in Waltham,
Massachusetts and Princeton, New Jersey. For additional information, please
visit GPC Biotech's Web site at gpc-biotech.



This press release contains forward-looking statements, which express
the current beliefs and expectations of the management of GPC Biotech AG,
including summary statements relating to topline results of the SPARC
trial, initial clinical results with the 1D09C3 monoclonal antibody and
summary statements relating to the potential efficacy and safety profile of
satraplatin and of 1D09C3. Such statements are based on current
expectations and are subject to risks and uncertainties, many of which are
beyond our control, that could cause future results, performance or
achievements to differ significantly from the results, performance or
achievements expressed or implied by such forward-looking statements.
Actual results could differ materially depending on a number of factors,
and we caution investors not to place undue reliance on the forward-looking
statements contained in this press release. In particular, there can be no
guarantee that results from the clinical trials discussed in this press
release will be confirmed upon full or final analysis of the results of the
trials and additional information relating to the safety, efficacy or
tolerability of satraplatin or of 1D09C3 may be discovered upon further
data analysis. We cannot guarantee that satraplatin or 1D09C3 will be
approved for marketing in a timely manner, if at all, by regulatory
authorities nor that, if marketed, either product will be a commercial
success . We direct you to GPC Biotech's Annual Report on Form 20-F for the
fiscal year ended December 31, 2005 and other reports filed with the U.S.
Securities and Exchange Commission for additional details on the important
factors that may affect the future results, performance and achievements of
GPC Biotech. Forward-looking statements speak only as of the date on which
they are made and GPC Biotech does not undertake any obligation to update
these forward-looking statements, even if new information becomes available
in the future.



The scientific information discussed in this press release related to
satraplatin and to 1D09C3 is preliminary and investigative. Neither
satraplatin nor 1D09C3 has been approved by the FDA in the U.S., the EMEA
in Europe or any other regulatory authority and no conclusions can or
should be drawn regarding its safety or effectiveness. Only the relevant
regulatory authorities can determine whether satraplatin and 1D09C3 are
safe and effective for the use(s) being investigated.

Alexion's Soliris(R) Receives 2009 Prix Galien France For Most Innovative Drug For Rare Disease

Alexion Pharma France and Alexion Pharmaceuticals, Inc. (NASDAQ: ALXN) today received the 2009 Prix Galien France for Soliris® (eculizumab) in the category of medicines for rare diseases. The award recognizes the scientific innovation represented by the complement-inhibition technology of Soliris, and the impact the drug is having on the lives of patients with paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare, debilitating and life-threatening blood disorder.


Soliris is a first-in-class terminal complement inhibitor that selectively blocks the formation of terminal complement, a component of the normal immune system. Patients with PNH lack naturally occurring proteins that ordinarily prevent terminal complement from causing the red blood cell destruction (hemolysis) that is central to the serious morbidities and mortality associated with PNH. The French award follows receipt last year by Alexion of the 2008 Prix Galien USA Award for Soliris as the Best Biotechnology Product with broad implications for future biomedical research.


"Alexion's employees in France and throughout Europe are gratified by this award and by the opportunity we have to improve the lives of patients with PNH," said Patrice Coissac, Senior Vice President of Alexion Pharmaceuticals, Inc. and President of Alexion International SГ rl. "Alexion is committed to the objective that every patient with PNH who can benefit from Soliris will have access to Soliris, and each day, we are working with physicians and national healthcare authorities in Europe toward this goal."


About the Prix Galien


The Prix Galien was established in France in 1970 by French pharmacist Roland Mehl to recognize and promote significant advances in pharmaceutical research. The award is among the industry's highest accolades. The French award committee includes 17 eminent members from the scientific, medical, and academic communities of France.


Since its debut in France, the Prix Galien has been introduced in other countries of Europe, as well as in the U.S. and Canada. As in France, a prominent and independent panel of judges selects the winner, based on the innovative aspects and therapeutic advantages of the recipients. In addition, an International Prix Galien is selected from winners of the country awards every two years.


"We deeply appreciate this honor, which recognizes more than 15 years of basic and clinical research in the field of complement inhibition," said Leonard Bell, M.D., Chief Executive Officer of Alexion. "We are building on the success of Soliris by increasing our understanding of PNH and by evaluating the promise of complement inhibition for the treatment of patients with other ultra-rare and life-threatening disorders."


About PNH


Patients with PNH suffer from hemolysis (red blood cell destruction) which leads to thromboses (blood clots), disabling fatigue, anemia, impaired quality of life, pulmonary hypertension, shortness of breath, recurrent pain, kidney disease and intermittent episodes of dark-colored urine (hemoglobinuria). (1,2) PNH is an ultra-rare blood disorder that strikes people of all ages, with an average age of onset in the early 30s. (3) Approximately 10 percent of all patients first develop symptoms at 21 years of age or younger. (1) PNH develops without warning and can occur in men and women of all races, backgrounds and ages. PNH often goes unrecognized, with delays in diagnosis ranging from one to more than 10 years. (4) It is estimated that approximately one-third of patients with PNH do not survive more than five years from the time of diagnosis. (4) PNH has been identified more commonly among patients with disorders of the bone marrow, including aplastic anemia (AA) and myelodysplastic syndromes (MDS). (5,6,7) In patients with thrombosis of unknown origin, PNH may be an underlying cause. (1) More information on PNH is available at pnhsource.















About Soliris


Soliris has been approved by the U.S. Food and Drug Administration (March 2007), the European Commission (June 2007), Health Canada (January 2009) and Australia's Therapeutic Goods Administration (February 2009) as the first treatment for all patients with paroxysmal nocturnal hemoglobinuria (PNH), an ultra-rare, debilitating and life-threatening blood disorder defined by hemolysis, or the destruction of red blood cells. All four jurisdictions reviewed and approved their respective marketing applications for Soliris under their priority review or accelerated assessment procedures, and all four have designated Soliris as an orphan drug. Soliris is not approved for the treatment of transplant rejection. More information on Soliris is available at soliris.


About Alexion


Alexion Pharmaceuticals, Inc. is a biopharmaceutical company working to develop and deliver life-changing drug therapies for patients with serious and life-threatening medical conditions. Alexion is engaged in the discovery, development and commercialization of therapeutic products aimed at treating patients with a wide array of severe disease states, including hematologic and kidney diseases, transplant, cancer, and autoimmune disorders. Soliris is Alexion's first marketed product, approved in the U.S. and Europe in 2007, and Canada and Australia in 2009. Alexion is evaluating other potential indications for Soliris as well as other formulations of eculizumab for additional clinical indications, and is pursuing development of other antibody product candidates in early stages of development. This press release and further information about Alexion Pharmaceuticals, Inc. can be found at alexionpharma.


References


1. Parker C, Omine M, Richards S, et al. Diagnosis and management of paroxysmal nocturnal hemoglobinuria. Blood. 2005;106 (12):3699-3709.


2. Hill A, Richards S, Hillmen P. Recent developments in the understanding and management of paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2007;137:181-92.


3. SociГ© G, Mary J Yves, de Gramont A, et al. Paroxysmal nocturnal haemoglobinuria: long-term follow-up and prognostic factors. Lancet. 1996; 348:573-577.


4. Hillmen P, Lewis SM, Bessler M, Luzzatto L, Dacie JV. Natural history of paroxysmal nocturnal hemoglobinuria. N Engl J Med. 1995; 333:1253-1258.


5. Wang H, Chuhjo T, Yasue S, Omine M, Naka S. Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome. Blood. 2002;100 (12):3897-3902.


6. Iwanga M, Furukawa K, Amenomori T, et al. Paroxysmal nocturnal haemoglobinuria clones in patients with myelodysplastic syndromes. Br J Haematol. 1998;102 (2):465-474.


7. Maciejewski JP, Risitano AM, Sloand EM, et al. Relationship between bone marrow failure syndromes and the presence of glycophosphatidyl inositol-anchored protein-deficient clones. Br J Haematol. 2001;115:1015-1022.

Source
Soliris


View drug information on Soliris.

Red Grape Skin Extract Could Be New Treatment For Sickle Cell Disease Patients

An extract in red grape skin may be a new treatment for sickle cell disease, Medical College of Georgia researchers say.



The extract, resveratrol, a natural chemical typically found in red wine and various plants and fruits, has been found to induce production of fetal hemoglobin, which decreases the sickling of red blood cells and reduces the painful vascular episodes associated with the disease.



Most fetal hemoglobin production ceases after birth, but in patients where it remains the predominant form, it can result in fewer complications, says Davies Agyekum, a second-year Ph.D. student in the MCG School of Graduate Studies.



In sickle cell disease, abnormal hemoglobin causes red blood cells to sickle. The abnormal shape impedes blood's passage through vessels and can cause excruciating pain and other complications because of the blood's oxygen deficiency.



Davies is working with Dr. Steffen E. Meiler, vice chair of research for the Department of Anesthesiology and Perioperative Medicine, on an eight-week animal study to determine if the combined anti-inflammatory and fetal hemoglobin-producing properties of resveratrol, a dietary polyphenol, can reduce the severity of sickle cell disease.



Hydroxyurea, an anti-cancer agent and the only Food and Drug Administration-approved therapeutic drug for sickle cell disease, increases fetal hemoglobin. Davies says reseveratrol-based therapy might be easier on patients.



The Ghana native recently received a three- to five-year $15,000 scholarship from the Southern Regional Education Board State Doctoral Scholars Program, a program aimed at increasing the number of minority students who earn doctoral degrees and become college and university professors.



He is attending the organization's annual Institute on Teaching and Mentoring in Arlington, Va., today through Oct. 25, to learn success skills and prepare for a university-level teaching position.



"My ultimate career goal is to be in position where I can inspire future generation through teaching and mentoring, so I am ecstatic about the opportunity this scholarship presents," Davies says.



Davies earned a bachelor's degree in biology from Emmanuel College in Franklin Springs, Ga., and hopes to stay in Georgia to teach.



Source:
Amy Connell


Medical College of Georgia

U.S. Naval Medical Research Center Resubmits IND Application For Proposed 'Op RESUS' Clinical Trial In Trauma Patients In The Battlefield Setting

Biopure Corporation (Nasdaq: BPUR) announced that the U.S. Naval Medical Research Center (NMRC) has submitted to the Food and Drug Administration (FDA) a revised investigational new drug (IND) application to conduct a clinical trial of the company's oxygen therapeutic Hemopure(R) [hemoglobin glutamer - 250 (bovine)] for the pre hospital battlefield treatment of trauma patients. The study is entitled "Operation Restore Effective Survival in Shock" (Op RESUS).


As previously reported, in June 2008 the NMRC submitted and subsequently withdrew an Op RESUS protocol for a Phase 2 clinical trial of Hemopure for resuscitation of operations casualties with severe traumatic hemorrhagic shock, when blood transfusion is not available. The proposed trial hypothesis is that for such casualties Hemopure will improve survival and other clinical parameters, and will be relatively safe and well tolerated, in comparison with "standard fluid." If the trial is permitted to proceed, subjects will sign an informed consent prospectively. The revised Op RESUS protocol addresses some of the issues raised by the FDA on the initial filing.


Under a research agreement with Biopure, the NMRC assumed primary responsibility, subject to funding, for designing, seeking FDA acceptance of and directing a trial for Hemopure's prehospital use in trauma patients with hemorrhagic shock. The NMRC has developed protocols for trials in civilian casualties in the United States and abroad (RESUS) as well as Op RESUS. To date, Congress has appropriated funds for the development of Hemopure for potential use in military and civilian trauma indications and to cover military administrative costs. This funding is being used for trial preparation and for preclinical studies of Hemopure in animal models, including those that mimic military trauma scenarios. RESUS remains on clinical hold, and the Company anticipates that NMRC will also submit an amended version of that protocol.


Biopure Corporation


Biopure Corporation develops, manufactures and markets pharmaceuticals, called oxygen therapeutics that are intravenously administered to deliver oxygen to the body's tissues. Hemopure(R) [hemoglobin glutamer - 250 (bovine)], or HBOC-201, is approved for sale in South Africa for the treatment of surgical patients who are acutely anemic. On November 21, 2008, the Company announced that it had terminated most of its work force for financial reasons. Using its limited resources, the Company is developing Hemopure for other indications and is supporting the U.S. Navy's government-funded efforts to develop a potential out-of-hospital trauma indication. Biopure's veterinary product Oxyglobin(R) [hemoglobin glutamer - 200 (bovine)], or HBOC-301, the only oxygen therapeutic approved for marketing by both the U.S. Food and Drug Administration and the European Commission, is indicated for the treatment of anemia in dogs. Biopure has sold approximately 200,000 units of Oxyglobin since its launch.


Statements in this release that are not strictly historical are forward-looking statements, including any statements implying that any proposed trial will be permitted to proceed by the FDA or that if a trial is undertaken the results will be as expected. Actual results and their timing may differ materially from those projected in these forward-looking statements due to risks and uncertainties. These risks include, without limitation, uncertainties regarding the company's financial position, including its limited cash resources and need to raise additional capital to pursue its business, unexpected costs and expenses, delays and adverse determinations by regulatory authorities, unanticipated problems with the product's commercial use, whether or not product related, and with product distributors, sales agents or other third parties, delays in clinical trials, and the other factors identified under the heading "Risk Factors" in the Company's quarterly report on Form 10-Q filed on September 15, 2008, which can be accessed in the EDGAR database at the U.S. Securities and Exchange Commission's (SEC) website, sec. The company undertakes no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof. A full discussion of the company's operations and financial condition can be found in the company's filings with the SEC.


Biopure Corporation

biopure

Sickle Cell Treatment Developed At LA BioMed Approved For Phase 3 Clinical Trial

The Food and Drug Administration (FDA) gave its approval this week for Emmaus Medical, Inc. to begin a Phase 3 clinical trial of an experimental treatment for sickle cell disease. The patented experimental treatment was originally developed by investigators led by Yutaka Niihara, MD, MPH, at the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center (LA BioMed) and is licensed to Emmaus Medical.


The patented drug treatment involves the oral administration of L-glutamine, which is the most common amino acid in the body. This is one of a very few experimental treatments for sickle cell disease to reach the Phase 3 clinical trial stage.


"News of this clinical trial should be of great interest to the millions of people around the world who suffer from painful crises caused by sickle cell disease," said Dr. Niihara. "Phase 3 clinical trials are large, randomized studies conducted at multiple sites to determine the safety and efficacy of a potential treatment. Phase 3 clinical trials are usually the last clinical trials conducted before FDA approval is obtained and the treatment can be made widely available to the patient population."


Sickle cell disease is an inherited disorder that causes red blood cells to become oxidized, sticky and sickle shaped instead of smooth, pliable and round. Sickle cell disease leads to anemia, organ damage, chronic and acute pain and a host of other problems.


"In our Phase 2 clinical trial, we observed an excellent safety profile and positive trends in reducing the number of crises and hospitalizations in sickle cell disease patients," said Dr. Niihara. "We look forward to initiating the Phase 3 clinical trial and remain committed to developing a treatment for sickle cell disease."


Emmaus Medical, Inc. was founded in Torrance, CA in 2000 as a private company to develop new treatments for sickle cell disease and other rare diseases. Emmaus Medical works closely with LA BioMed in developing these treatments. Emmaus' first product, NutreStore™ [L-glutamine powder for oral solution], together with Zorbtive® [somatropin (rDNA origin) for injection] and a specialized oral diet, is the only FDA-approved therapy for short bowel syndrome. For more information, please visit emmausmedical or call 310-214-0065.



About LA BioMed


LA BioMed at Harbor-UCLA Medical Center is one of the country's largest nonprofit independent biomedical research institutes. It conducts biomedical research, trains young scientists and provides community services, including childhood immunization and nutrition assistance. The institute's researchers conduct studies in such areas as cardiovascular disease, emerging infections, cancer, diabetes, kidney disease, dermatology, reproductive health, vaccine development, respiratory disorders, inherited illnesses and neonatology. LA BioMed is academically affiliated with the David Geffen School of Medicine at UCLA. For more information, please visit our website at LABioMed

Source
LA BioMed

High Triglyceride Levels Common, Often Untreated Among Americans

High concentrations of blood fats known as triglycerides are common in the United States, according to a report in the March 23 issue of Archives of Internal Medicine, one of the JAMA/Archives journals. Lifestyle changes are the preferred initial treatment for hypertriglyceridemia (the resulting condition), but physical inactivity, obesity and other modifiable risk factors remain prevalent.



"Increasing evidence supports triglyceride concentration as a risk factor for cardiovascular disease," the authors write as background information in the article. "If triglyceride concentrations are indeed a risk factor for cardiovascular disease, then it becomes important to establish the prevalence of hypertriglyceridemia in the U.S. population and to learn about the degree of pharmacologic management of this risk factor."



Earl S. Ford, M.D., M.P.H., and colleagues at the Centers for Disease Control and Prevention, Atlanta, examined data for 5,610 participants age 20 or older who participated in the National Health and Nutrition Examination Surveys between 1999 and 2004. The 2,837 men and 2,773 women were interviewed at home and then invited to attend a mobile examination center, where they answered additional questions, underwent examinations and provided blood samples.



A total of 33.1 percent of participants had a triglyceride concentration of 150 milligrams per deciliter or higher (between 150 and 199 milligrams per deciliter is defined as borderline high by the 2001 National Cholesterol Education Program report), 17.9 percent had a concentration of 200 milligrams per deciliter or higher (defined as high), 1.7 percent had a concentration of 500 milligrams per deciliter or higher and 0.4 percent had a concentration of 1,000 milligrams per deciliter or higher.



Compared with those who did not have hypertriglyceridemia, those who did were more likely to be older, be white, have not pursued an education beyond high school, smoke, be overweight or obese or have diabetes. "An important approach to the patient with hypertriglyceridemia is the implementation of non-pharmacological interventions," the authors write. "The high percentages of participants with a triglyceride concentration of 200 milligrams per deciliter or higher who were overweight or obese, who failed to engage in physical activity for approximately 150 minutes per week or who smoked attest to the challenge confronting health care providers in working with their patients to implement therapeutic lifestyle changes."



A total of 1.3 percent of participants used one of three prescription medications (fenofibrate, gemfibrozil or niacin) that treat hypertriglyceridemia, including 2.6 percent of those with a concentration of 150 milligrams per deciliter or higher and 3.6 percent of those with a concentration of 200 milligrams per deciliter or higher. This may reflect uncertainty about the need to treat this abnormality, the authors note. The benefits of pharmacotherapy are clear for patients with levels of 500 milligrams per deciliter or higher, who are at risk for pancreatitis, but therapeutic lifestyle changes remain the initial therapy of choice for those with levels between 200 and 500 milligrams per deciliter.



"As research clarifies uncertainties in the relation between triglyceride concentration and cardiovascular disease, guidelines to treat hypertriglyceridemia will likely be modified," they conclude.



Arch Intern Med. 2009;169[6]:572-578



archinte.ama-assn



View drug information on Fenofibrate.

Research Into Trace Minerals' Nutritional Alliance Boosted By Grant

Iron is the workhorse of trace minerals. An essential component of red blood cells, disruption of iron levels in the body will result in a myriad of serious conditions, and life cannot be sustained without it.


In novel research, investigators at the University at Buffalo's School of Public Health and Health Professions, have learned that iron is only one half of an all-important duo of trace minerals -- the other being copper -- that work in tandem to maintain proper iron balance, or homeostasis. It appears the workhorse has a helper. James F. Collins, Ph.D., UB assistant professor of exercise and nutrition sciences and biochemistry, discovered that when iron-absorption by cells lining the small intestine decreases during iron-deficient states, copper absorption increases.



Collins now is exploring the relationship between these two trace minerals through a $1.38 million grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The work will be carried out using established models of intestinal iron absorption in humans, including iron and iron/copper-deficient rodents and cultured intestinal epithelial cells.



"This project is intended to test the overall hypothesis that increased copper transport during iron-deficiency is critical to enhance certain aspects of intestinal iron absorption," said Collins. "Iron or copper deficiency causes anemia, and abnormal intestinal iron transport is associated with several common human pathologies, including anemia of chronic disease (ACD) and hereditary hemochromatosis (HH), different forms of which result from several common genetic defects."



HH is an inherited metabolic disorder characterized by abnormally high absorption of dietary iron, which is deposited in body tissues and organs, where it may become toxic. ACD is a blood disorder caused by low body iron levels resulting from any medical condition that affects the production and lifespan of red blood cells, such as chronic infection, chronic immune activation resulting in inflammation, or malignancy.



"In collaboration with Dr. Zihua Hu, Ph.D., a computational scientist at UB's New York State Center of Excellence in Bioinformatics and Life Sciences, we determined that several genes related to iron and copper homeostasis were strongly induced by iron deprivation across different developmental stages in the rat small intestine," said Collins. "We will concentrate on understanding the role of two key proteins encoded by these genes: an intestinal iron transporter called divalent metal transporter 1 (Dmt1) and an intestinal copper transporter, the Menkes copper ATPase (Atp7a)."



The overall goal of the project is to answer three specific questions regarding the role of copper in intestinal iron transport, Collins noted:

Are Atp7a and Dmt1 solely responsible for enhancing dietary copper absorption during iron-deficiency?
What are the molecular mechanisms leading to induction of the Atp7a and Dmt1 genes?
Which physiological processes related to intestinal iron ion homeostasis are enhanced by increased copper levels in enterocytes (cells of the superficial layer of the intestines) and in the liver?
"We also expect to learn more about the mechanisms of dietary copper absorption, which currently are not well defined," Collins said. "Furthermore, studies addressing the impact of increased enterocyte and liver copper levels during iron-deficiency have not been reported in the scientific literature to date, so this investigation is novel. "






Key collaborators at UB are Hu, Michael D. Garrick, Ph.D., professor of biochemistry, and Laura M. Garrick, Ph.D., research associate professor of biochemistry. The University at Buffalo is a premier research-intensive public university, the largest and most comprehensive campus in the State University of New York. UB's more than 27,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities. The School of Public Health and Health Professions is one of five schools that constitute UB's Academic Health Center.



Source: Lois Baker


University at Buffalo