DREAM DRUGS: Drugs at the Clinical Stage — In the Pipeline

The Biotech-100 Index includes 100 small cap biotechnology stocks whose product drug pipeline contain at least one drug in either phase II and/or Phase III clinical development. There is a 90% chance of rejection in early-stage phase I clinical trials; a 50% chance in phase II; 20% in phase III; and 10% post-phase III. Companies that are in phase II and III tend to show great promise but still have a high degree of volatiliy.

Pipeline Drugs Company Symbol
ABX-EGF (panitumumab) Abgenix ABGX targets the epidermal growth factor receptor (EGFr), which is over-expressed in a variety of cancers including lung cancer, breast cancer, bladder, pancreatic, colorectal cancer, kidney and head and neck cancer.
ABX-MA1 Abgenix ABGX ABX-MA1 targets a protein called MUC18, a cell-surface adhesion molecule that is highly expressed on metastatic melanoma cells but not on normal skin cells
ACP-103 Acadia ACAD Parkinson’s Disease, adjunctive therapy forschizophrenia (Hallucinations, Psychoses)
Onconase (ranpirnase) AlfaCell ACEL Ribonuclease anti-cancer drug,
Entereg (alvimopan) Adolor ADLR pain management of POI and OBD
lidocaine patch Adolor ADLR postoperative incisional pain
perifosine Æterna Zentaris Inc AEZS Multiple myeloma and advanced metastatic colorectal cancer — multiple cancers
SolorelTM (AEZS-130) Æterna Zentaris Inc AEZS Growth hormone secretagogue– potential applications for the treatment of cachexia
AEZS-108 Æterna Zentaris Inc AEZS Ovarian cancer, endometrial cancer
AG-858 Antigenics Inc. AGEN Chronic myelogenous leukemia (CML)
Oncophage Antigenics Inc. AGEN Metastatic melanoma, Kidney cancer (renal cell carcinoma)
AG-702 Antigenics Inc. AGEN Genital herpes
V -Protectants® (AGI-1067) Atherogenics AGIX chronic inflammatory diseases, such as atherosclerosis, rheumatoid arthritis andasthma
Vivitrex Alkermes ALKS Alchol Dependence
Medisorb Alkermes ALKS Diabetes
AIR Insulin Alkermes ALKS Diabetes
AIR Epinephrine Alkermes ALKS Anaphylaxis
Pexelizumab Alexion ALXN Cardiopulmonary Bypass, Acute Myocardial Infarction
Eculizumab Alexion ALXN Nephritis, Dermatomyositis , Paroxysmal Nocturnal Hemoglinuria
Efaproxiral Allos Therapeutics ALTH Brain metastases from breast cancer, non-small cell lung cancer, cervical cancer
PDX (pralatrexate) Allos Therapeutics ALTH non-small cell lung cancer, Mesothelioma, non-Hodgkin’s Lymphoma
SYMLIN® (pramlintide acetate) Amylin AMLN synthetic version of human amylin -glucose control with type 1 diabetes
exenatide (synthetic exendin-4) Amylin AMLN type 2 diabetes
Isatoribine (ANA245) Anadys ANDS Hepatitis C
ANA 380 Anadys ANDS Hepatitis B
Oral Prodrug ANA971 Anadys ANDS reduce the risk of HCV relapse
AMD3100 AnorMED AOM.TO stem cell mobilizer
AMD070 AnorMED AOM.TO chemokine inhibitor for HIV
Insegia(G17DT immunogen) Aphton Corp APHT cancer and gastrointestinal disease
AP23573 Ariad ARIA solid tumor and blood malignancies
TP10 Avant AVAN Cardiac Surgery
CETi-I Avant AVAN Cholesterol Management
CholeraGarde Avant AVAN Cholera
Ty800 Avant AVAN Typhoid Fever
Injectable Anthrax Avant AVAN Anthrax
Therapore Avant AVAN HIV
Resten-NG Avi Biopharma AVII cardiovascular restenosis
Avicine Avi Biopharma AVII vaccine — anti-hCG immune response targeting hCG-producing cancer cells
NeuGene compounds Avi Biopharma AVII anti-sense drugs for cancer, polycystic kidney disease, and viral diseases
Neurodex Avanir AVN pseudobulbar affect, neuropathic pain
Avanir Avanir AVN Asthma
AV201 Avigin AVGN severe Parkinson’s disease
Phenserine Axonyx AXYX Alzheimer’s disease
Theratope Vaccine Biomira BIOM colorectal, metastatic breast cancer
BLP25 Liposome Vaccine Biomira BIOM Prostate, non-small cell lung cancer
Modrenal Bioenvision BIVN Prostate Cancer
Clofarabine (CLOLAR) Bioenvision BIVN pediatric acute lymphoblastic leukemia, solid Tumors
Velostan Bioenvision BIVN post-menopausal advanced breast cancer,bladder cancer
virostat Bioenvision BIVN hepatitis C
GVAX (vaccine) Cell Genesys CEGE Prostate, lung, pancreatic, leukemia, myeloma
CG7870 Oncolytic Virus Therapy Cell Genesys CEGE Prostate cancer
Daptomycin (cubicin) Cubist CBST soft tissue infection, infective endocarditis
HepeX-B Cubist CBST prevention of infection by hepatitis B in liver transplant
Oracea Collagenex Pharmaceuticals Inc CGPI rosacea
E2F Decoy Corgentech CGTK Coronary Bypass Graft, Arterio-Venous Graft
mifepristone ( Corlux) Corcept CORT Psychotic major depression, Alzheimers
Ventavis CoTherix Inc CTRX pulmonary arterial hypertension
Ranexa CV Therapeutics Inc CVTX Chronic Angina
Regadenoson CV Therapeutics Inc CVTX Myocardial Perfusion Imaging
Tecadenoson CV Therapeutics Inc CVTX (PSVT Atrial Fibrillation)
Adentri CV Therapeutics Inc CVTX congestive heart failure (CHF)
Milnacipran Cypress Biosciences CYPB fibromyalgia syndrome (FMS) and related chronic pain conditions
SB-715992 Cytokinetics CYTK multiple forms of cancer, including combination therapy
provenge Dendreon DNDN prostate cancer vaccine
APC8024(Neuvenge) Dendreon DNDN HER-2/neu positive cancers, including breast,ovarian and colorectal cancers
indiplon DOV Pharmaceuticals DOVP insomnia
bicifadine DOV Pharmaceuticals DOVP pain
ocinaplon DOV Pharmaceuticals DOVP generalized anxiety disorder
DOV 216,303 DOV Pharmaceuticals DOVP depression, anxiety and substance abuse
DOV Diltiazen DOV Pharmaceuticals DOVP Angina and Hypertension
DX-88 Dyax DYAX hereditary angioedema (HAE)
DX-890 Dyax DYAX cystic fibrosis (CF),chronic obstructive airways diseases
Thelin (sitaxsentan) Encysive Pharmaceuticals ENCY pulmonary arterial hypertension (PAH)
BIMOSIAMOSE Encysive Pharmaceuticals ENCY inhaled therapy for asthma, psoriasis and atopic dermatitis
TBC3711 Encysive Pharmaceuticals ENCY endothelin A antagonis
Panzem (2-methoxyestradiol) EntreMed ENMD cancer
XL119 Exelixis EXEL bile duct tumors
Macugen(pegaptanib sodium injection) Eyetech Pharmaceuticals EYET wet form of age-related macular degeneration (AMD)
FM-VP4 Forbes Medi-Tech FMTI cholesterol-lowering and anti-atherosclerotic
Genasense® (oblimersen sodium Genta GNTA melanoma, lung and prostate cancers
Ganite® (gallium nitrate injection). Genta GNTA cancer related hypercalcemia
TNFerade GenVec GNVC Tumor necrosis factor alpha gene
TVAX Telomerase Cancer Vaccine (TVAX) Geron GERN prostate cancer
Aquavan Injection Guilford Pharmaceuticals GLFD mild to moderate sedation for non-invasive procedures
GPI 1485 Guilford Pharmaceuticals GLFD Impotence, Prostate Cancer
GPI 5693 Guilford Pharmaceuticals GLFD neuropathic pain
MyVax Genitope Corp GTOP idotypic vaccine for cancer follicular non-Hodgkin’s lymphoma (f-NHL).
ACAPODEME GTX Inc. GTXI Prevention of prostate cancer in men with high grade PIN
Andarine GTX Inc. GTXI Cachexia from various types of cancer
Ostarine GTX Inc. GTXI andropause
HE2100 NEUMUNE Hollis-Eden Pharmaceuticals HEPH protecting the body’s bone marrow from acute radiation syndrom
PHOSPHONOL Hollis-Eden Pharmaceuticals HEPH protect against DNA mutations (mutagenesis)– from radiation
(HE2000) IMMUNITIN Hollis-Eden Pharmaceuticals HEPH Malaria and HIV and preclinical benefit in a number of tuberculosis model
LymphoStat-B Human Genome Sciences HGSI drugs discovered through genomics-based research
Albuferon Human Genome Sciences HGSI hepatitis C, b?? and a broad range of cancers
HGS-ETRI Human Genome Sciences HGSI apoptosis, in cancer cells.
HGS-TR2J Human Genome Sciences HGSI apoptosis, in cancer cells.
480848 Human Genome Sciences HGSI inhibits atherosclerotic plaques
IC485 ICOS ICOS Chronic Obstructive Pulmonary Disease
Tadalafil ICOS ICOS Benign Prostatic Hyperplasia
FluINsure ID Biomedical Corp IDBE vaccine prevention of influenza (flu)
StreptAvax ID Biomedical Corp IDBE vaccine for prevention of diseases caused by group A streptococcus in children
PPV ID Biomedical Corp IDBE vaccine for the prevention of disease caused by Streptococcus pneumoniae (pneumococcus)
Pagocione Indevus Pharmaceuticals IDEV Stuttering
PRO2000 Indevus Pharmaceuticals IDEV HIV and STD Prevention
IP 751 Indevus Pharmaceuticals IDEV Pain and Inflammation
Aminocandin Indevus Pharmaceuticals IDEV Serious Fungal Infections
HuN901-DM1 Immunogen IMGN cancers that express the CanAg antigen
MLN2704 Immunogen IMGN -targets the prostate-specific membrane antigen (PSMA)
Cantuzumab mertansine Immunogen IMGN cancers that express the CanAg antigen
Reverset Incyte Corp INCY HIV
CCR2 Antagonists Incyte Corp INCY Rheumatoid Arthritis, MS, Neuropathic Pain, Atherosclerosis
Sheddase Inhibitors Incyte Corp INCY Cancer
ADVEXIN Introgen Therapeutics INGN Cancer ?? Advexin (adenoviral p53) —bladder cancer--gene therapy -PI
INGN 241 Introgen Therapeutics INGN tumor suppressor product candidate
INGN 225 Introgen Therapeutics INGN tumor vaccine
Visicol InKline Pharamceuticals INKP Constipation
INKP-102 InKline Pharamceuticals INKP Colon cleansing prior to colonoscopy
IB-Stat InKline Pharamceuticals INKP Symptoms associated with Irritable Bowel Syndrome (IBS)
CEA-Scan Immunomedics IMMU targets tumors that have carcinoembryonic antigen (CEA) on their cell membrane
antisense drugs ISIS Pharmaceuticals ISIS ulcerative colitis, diabetes, MS, cardiovascular disease, cancer, psoriasis
diquafosol tetrasodium (INS365 Ophthalmic) Inspire Pharamceuticals ISPH for the treatment of dry eye disease
INS37217– Respiratory (denufosol tetrasodium) Inspire Pharamceuticals ISPH cystic fibrosis, retinal disease
IN50589 Inspire Pharamceuticals ISPH Antiplatelet for Platelet Inhibition
Sulodexide (KRX-101) Keryx Biopharmaceuticals KERX diabetic nephropathy
Perifosine (KRX-0401) Keryx Biopharmaceuticals KERX multiple forms of cancer
KS 01-019 Kos Pharmaceuticals KOSP dyslipidemia
KS 01-018 Kos Pharmaceuticals KOSP Periperhal Arterial Disease
Azmacort Kos Pharmaceuticals KOSP treatment of asthma as prophylactic therapy
Targretin Ligand Pharmaceuticals LGND non-small cell lung cancer
ONTAK Ligand Pharmaceuticals LGND B- and T-cell non-Hodgkin’s lymphomas and chronic lymphocytic leukemia,
Targretin gel Ligand Pharmaceuticals LGND hand dermatitis
LJP 394 La Jolla Pharmaceuticals LJPC Lupus Erythematosus, Systemic Lupus Nephritis
Riquent® (abetimus sodium La Jolla Pharmaceuticals LJPC systemic lupus erythematosus (SLE)
Ceplene Maxim Pharmaceuticals MAXM Advanced Melanoma, Acute Myeloid Leukemia, Renal Cell Carcinoma, Hepatitis C
Medarex Antibodies Medarex MEDX cancer, inflammation, autoimmune and infectious diseases
Anidulafungin Vicuron Pharmaceuticals MICU anti-fungal
Dalbavancin Vicuron Pharmaceuticals MICU glycopeptide class of antibiotics (hospital infections)
Oxazolidinones Vicuron Pharmaceuticals MICU most-difficult-to-treat, multi-drug-resistant bacteria
Deformylase Inhibitors Vicuron Pharmaceuticals MICU antibiotic — respiratory tract infections
INTEGRILIN® (EPTIFIBATIDE) Millenium Pharmaceuticals MLNM cardiovascular
VELCADE® (bortezomib)- Millenium Pharmaceuticals MLNM lung, breast, prostate cancers
MLN1202,MLN2704 Millenium Pharmaceuticals MLNM Rheumatoid arthritis, multiple sclerosis,inflammation
Technosphere Insulin System MannKind Corp MNKD pulmonary delivery system for diabetes
Enoximone Myogen MYOG Advanced Chronic Heart Failure
Ambristentan Myogen MYOG Pulmonary Arterial Hypertension
Darusentan Myogen MYOG Uncontrolled Hypertension
Flurizan Myriad Genetics Inc MYGN Alzheimer’s, cancer
StaphVAX Nabi Biopharmaceuticals NABI Vaccine for staphylococcus infections
NicVax Nabi Biopharmaceuticals NABI Vaccine for smoking cessation vaccine
Civacir Nabi Biopharmaceuticals NABI Hepatitis C antibody-based therapies
IL13-PE38QQR NeoPharm Inc NEOL Glioblastoma Multiforme brain tumor
Liposomal SN38 NeoPharm Inc NEOL Advanced cancers; including colorectal and lung
Liposomal c-raf Antisense Oligonucleotide NeoPharm Inc NEOL Advanced cancers; including pancreatic (monotherapy and combination with radiation/chemotherapy)
Liposomal Paclitaxel-Easy-to-use NeoPharm Inc NEOL Advanced cancers; including breast cancer, lung and ovarian
Indiplon Neurocrine Biosciences NBIX insomnia via inhibitory neurotransmitterGABA
CRF Receptor Antagonis Neurocrine Biosciences NBIX Anxiety and depression
NBL- 5788 Neurocrine Biosciences NBIX Multiple Sclerosis
Urocortin 2 Neurocrine Biosciences NBIX Acute congestive heart failure (CHF)
GnRH antagonists Neurocrine Biosciences NBIX Endometriosis
PREOS® (recombinant human parathyroid hormone) NPS Pharmaceuticals NPSP treatment of osteoporosis
Teduglutide NPS Pharmaceuticals NPSP gastrointestinal disorders including Short Bowel Syndrome
Preotact NPS Pharmaceuticals NPSP Osteoperosis
Calcilytics NPS Pharmaceuticals NPSP Osteoperosis
GlyT-1 NPS Pharmaceuticals NPSP Schizophrenia
Fibrillex Neurochem Inc. NRMX AA Amyloidosis
Alzhemed Neurochem Inc. NRMX Alzheimer’s Disease –inhibit the AmyloidCascade
Cerebril Neurochem Inc. NRMX Hemorrhagic stroke due to cerebral amyloidangiopathy
Memantine (Namenda) Neurobiological Tech NTII progressive neurological impairment due to neuronal injur
XERECEPT — natural human peptide CRF Neurobiological Tech NTII inhibitor of swelling, or edema
VIPRINEX™ (ancrod) Neurobiological Tech NTII stroke patients — anticoagulation
BiDil NitroMed NTMD Heart failure, or end-stage cardiovascular disease
Alfimeprase Nuvelo NUVO thrombolytic agent or blood clot dissolver
rNAPc2 Nuvelo NUVO Factor VIIa / Tissue Factor Inhibitor
ARC183 Nuvelo NUVO DNA-based direct thrombin inhibitor–anticoagulant / anti-thrombotic
BAY 43-9006 Onyx Pharmaceuticals ONXX advanced renal (kidney) cancer
Ramoplanin Oscient Pharmaceuticals OSCI Clostridium difficile-associated diarrhea
FACTIVE Oscient Pharmaceuticals OSCI Intravenous– Bacterial Infections
CA4P (combretastatin)– Oxigene OXGN Vascular targeting agent ??CK PHASE
Motexafin gadolinium Pharmacyclics Inc. PCYC anti-cancer product
Motexafin lutetium Pharmacyclics Inc PCYC reduce or eliminate “vulnerable plaque ”
Apan Praecis Pharmaceuticals PRCS Alzheimer’s Disease
PPI-2458 Praecis Pharmaceuticals PRCS Non-Hodgkin’s Lymphoma/RA
MNTX Progenics Pharmaceuticals PGNX Advanced medical ilness, post-operative ileus, chronic pain
GMX Progenics Pharmaceuticals PGNX Melanoma Cancer
PSMA Progenics Pharmaceuticals PGNX prostate cancer
PRO542 Progenics Pharmaceuticals PGNX HIV
PRO 140 Progenics Pharmaceuticals PGNX HIV
Trexima POZEN Inc. POZN migraine pain
OXYTREX Pain Therapeutics Inc. PTIE severe chronic pain, such as low back, osteoarthritic pain or cancer pain
REMOXY Pain Therapeutics Inc. PTIE proprietary abuse-resistant version of time-release oxycodone
PTI-901 Pain Therapeutics Inc. PTIE chronic Irritable Bowel Syndrome (IBS).
AXOKINE IL-1 Regeneron Pharmaceuticals REGN potential treatment of obesity
VEGF Trap Regeneron Pharmaceuticals REGN inihibits tumor blood vessel growth
L-4/13 Trap Regeneron Pharmaceuticals REGN treatment in allergy and asthma
IL-1 Trap Regeneron Pharmaceuticals REGN decreases inflammation and blocks cartilage erosion in the joint — Rhematoid Arthritis
ZADAXIN Sciclone Pharmaceuticals SCLN viral infections– hepatitis C, and cancer
SCV-07 Sciclone Pharmaceuticals SCLN fight infection
SGN-30 Seattle Genetics SGEN Hodgkin’s disease and some types of non-Hodgkin’s lymphoma
SGN-15 Seattle Genetics SGEN non-small cell lung cancer
SGN-40 Seattle Genetics SGEN multiple myeloma and non-Hodgkin’slymphoma
XIFAXAN™ (rifaximin) Salix Pharmaceuticals SLXP gastrointestinal- selective, oral antibiotic
ZEGERID Santarus Inc SNTS Heartburn/GERD, Erosive esophagitis, Duodenal ulcers
Orathecin Supergen Inc. SUPG pancreatic cancer
Avicine™ Supergen Inc. SUPG colorectal cancer
Satraplatin Spectrum Pharmaceuticals SPPI Prostate Cancer
SPI-153 Spectrum Pharmaceuticals SPPI Hormone Depenmdent Prostate Cancer
EOquin Spectrum Pharmaceuticals SPPI Bladder Cancer, Radiation Sensitizer
Elsamitrucin Spectrum Pharmaceuticals SPPI Non-Hodgkin’s Lymphoma
prosaptide Savient SVNT peripheral neuropathic pain
puricase Savient SVNT symptomatic gout
fibrimage Savient SVNT diagnostic agent for the detection of deep veinthrombosis
I2S Transkaryotic Therapies TKTX Hunter syndrome
GA-GCB Transkaryotic Therapies TKTX Gaucher disease
TELCYTA (TLK286) Telik Inc. TELK advanced ovarian cancer and non-small cell lung cancer (a selective apoptotic agent)
TELINTRA Telik Inc. TELK myelodysplastic syndrome –Bone marrow stimulant
TNX -355 Tanox Inc. TNOX HIV
T-1249 Trimeris Inc. TRMS HIV
Pivanex Titan Pharmaceuticals TTP Refractory Chronic Lymphocytic Leukemia
DITPA Titan Pharmaceuticals Congestive Heart Failure
Probuphine Titan Pharmaceuticals Opiate addition
Spheramine Titan Pharmaceuticals Advanced Parkinson’s
Iloperidone Titan Pharmaceuticals Schizophrenia
Gallium Maltolate Titan Pharmaceuticals Bone Disease
OvaRex United Therapeutics Corp UTHR Ovarian Cancer
Remodulin United Therapeutics Corp UTHR Critical limb ischemia (CLI)
UT-231B United Therapeutics Corp UTHR Hepatitis C
Celacade Vasogen Inc. VSGN Chronic Heart Failure, Periperheral Arterial Disease
VP025 Vasogen Inc. VSGN Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis
VX-385 Vertex Pharmaceuticals VRTX HIV infection
Merimepodib Vertex Pharmaceuticals VRTX hepatitis C
VX-950 Vertex Pharmaceuticals VRTX hepatitis C
VX-765 Vertex Pharmaceuticals VRTX cytokine inhibitor of interleukin-1 beta converting enzyme (ICE)
VX-702 Vertex Pharmaceuticals VRTX acute coronary syndromes
Pralnacasan Vertex Pharmaceuticals VRTX inflammatory diseases
VX944, VX630 Vertex Pharmaceuticals VRTX Cancer
DNA Vaccines Vical Inc VICL malaria, cytomegalovirus, eboa, west nile virus, hiv, hepatitis
Avanafil Vivus Inc. VVUS erectile dysfunction
ALISTA Vivus Inc. VVUS female sexual arousal disorder
Testosterone MDTS Vivus Inc. VVUS low sexual desire
Evamist Vivus Inc. VVUS symptoms associated with menopause
Neuprex XOMA LTD XOMA immunologic and inflammatory disorders, cancer and infectious diseases
MLN2222 XOMA LTD XOMA coronary artery bypass graft (CABG) surgery patients.
TransMID Xenova Group XNVA Glioblastoma multiforme (GBM)
XR303 Xenova Group XNVA Pancreatic Cancer
XR5944/XR11576 Xenova Group XNVA Solid Tumors
TA-CD Vaccine Xenova Group XNVA Cocaine addition
TA_NIC Vaccine Xenova Group XNVA Nicotine Addiction
Recombinant human Thrombin Zymogenetics Inc. ZGEN control of bleeding associated with various surgical procedures
-TACI-Ig Zymogenetics Inc. ZGEN autoimmune diseases and for advanced B-cell malignancies
Interleukin 21 (IL-21) Zymogenetics Inc. ZGEN cancer

source: http://www.pipelinedrugs.com/


Act Now Against Cipro! The FDA is Ready!

Clueless Doctors & Scientists

Cipro is only one killer of many in the fuoroquinolone class antibiotics!

As some of you may know, I have filed at the FDA a Citizen’s Petition again the antibiotic drug class fluoroquinolones, the most frequently prescribed antibiotics today. I started my attack with Cipro as guilty #1 since that is what nearly everyone gets and the number of people getting sick from Cipro is staggering. Cipro is now also understood to be the cause of the Gulf War Syndrome since soldiers were mandated to take it every day against anthrax in the field.

Many people have been permanently injured–some even have committed suicide. I am a firm believer that fibromyalgia is yet one more of the diseases we may be able to point to this class of drugs. The citizen petition docket is still open.

I just received a letter from the FDA stating that the matter is so complex that they…

View original post 71 more words

Researchers identify new target for anti-malaria drugs

A new target for drug development in the fight against the deadly disease malaria has been discovered by researchers at MIT.

In a paper published today in the journal Cell Host & Microbe, the researchers describe how they identified the drug target while studying the way in which the parasites Toxoplasma gondii, which causes toxoplasmosis, and Plasmodium, which causes malaria, access vital nutrients from their host cells.

Around one-third of the world’s deadly infectious diseases, including malaria and tuberculosis, are caused by pathogens that spend a large portion of their life inside specially built compartments within their host cells.

These compartments, known as “parasitophorous vacuoles,” separate the host cytoplasm and the parasite by a membrane, and thereby protect the parasites from the host cell’s defenses. They also provide an environment tailored to their needs, according to Dan Gold, a postdoc who led the research in the laboratory of Jeroen Saeij, the Robert A. Swanson Career Development Associate Professor of Life Sciences in MIT’s Department of Biology.

However, the membrane of these vacuoles also acts as a barrier between the parasite and the host cell. This makes it more difficult for the parasite to release proteins involved in the transformation of the host cell beyond the membrane in order to spread the disease, and for the pathogen to gain access to vital nutrients, Gold says.

“Ultimately what defines a parasite is that they require certain key nutrients from their host,” he says. “So they have had to evolve ways to get around their own barriers, to gain access to these nutrients.”

Previous research has shown that the vacuoles are selectively permeable to small molecules, allowing certain nutrients to pass through pores in the membrane. But until now, no one has been able to determine the molecular makeup of these pores, and how they are formed.

Two new proteins

When studying Toxoplasma, the researchers discovered two proteins secreted by the parasite, known as GRA17 and GRA23, which are responsible for forming these pores in the vacuole, Gold says.

The researchers discovered the proteins’ roles by accident, while investigating how the parasites are able to release their own proteins out into the host cell beyond the vacuole membrane after invasion.

Similar research into how the related Plasmodium pathogen performs this trick had identified a so-called “protein export complex” that transports encoded proteins from the parasite into its host red blood cell, which transforms these in a way that is vital to the spread of malaria. “The clinical symptoms of malaria are dependent on this process and this remodeling of the red blood cell that occurs,” Gold says.

The researchers identified proteins secreted by Toxoplasma that appeared to be homologues, or of shared ancestry to, this protein export complex in Plasmodium. But when they stopped these proteins from functioning, they found it made no difference to the export of proteins from the parasite beyond the vacuole.

“We were left wondering what GRA17 and GRA23 actually do, if they are not involved in protein export, and so we went back to look at this longstanding phenomenon of nutrient transport,” Gold says.

When they added dyes to the host cell, and again knocked out the two proteins, the researchers found that it prevented the dyes flowing into the vacuole. “That was our first indication that these proteins actually have a role in small-molecule transfer,” he says.

More significantly though, when the researchers expressed a Plasmodium export complex gene in the modified Toxoplasma, they found that the dyes were able to flow into the vacuole once again, suggesting that this small-molecule transport function had been restored.

“All of this came together to strongly suggest that this protein that is involved in export in Plasmodium may also have an additional function in small-molecule transport,” Gold says.

Limited effects

Crucially, since these proteins are only found in the parasite phylum Apicomplexa, to which both Toxoplasma and Plasmodium belong, they could be used as a drug target against the diseases they cause, including malaria, he says.

“This very strongly suggests that you could find small-molecule drugs to target these pores, which would be very damaging to these parasites, but likely wouldn’t have any interaction with any human molecules,” he says. “So I think this is a really strong potential drug target for restricting the access of these parasites to a set of nutrients.”

In addition to malaria, the technique could also be used to target the parasite Eimeria, which affects cattle and poultry, among other animals, and therefore has a huge economic cost, Gold says.

This “very exciting” research elegantly identifies a molecular component of a pore in the vacuole that separates the growing Toxoplasma parasite from its to help in the acquisition of nutrients, according to Manoj Duraisingh, a professor of immunology and infectious diseases at Harvard School of Public Health who was not involved in the research.

“Strikingly, this molecule is conserved for this function in the related and deadly parasite Plasmodium, where it was intriguingly found to be a part of a complex required for the export of proteins for the transformation of the host red blood cell and the virulence of the parasite,” Duraisingh says. “This suggests that a virulence determinant in Plasmodium parasites was co-opted from a basic function of parasitism broadly conserved in apicomplexan .”

Researchers make progress engineering digestive system tissues

New proof-of-concept research at Wake Forest Institute for Regenerative Medicine suggests the potential for engineering replacement intestine tissue in the lab, a treatment that could be applied to infants born with a short bowel and adults having large pieces of gut removed due to cancer or inflammatory bowel disease.


Lead researcher Khalil N Bitar, Ph.D., a professor at the institute, which is part of Wake Forest Baptist Medical Center, reported the results this week at Digestive Diseases Week in Washington, D.C. He also updated attendees on a related project to engineer anal sphincters for patients with fecal incontinence.

“Results from both projects are promising and exciting,” said Bitar. “Our latest effort, to find a new solution for the urgent need for gut-lengthening procedures, shows we can meet the basic requirements for regenerating segments of the gastrointestinal tract.”

Both projects are based on using a patient’s own cells to grow replacement tissue in the lab. Elie Zakhem, a doctoral student in Bitar’s lab, is currently working on developing tissue-engineered gut replacements. The researchers use and nerve stem cells from human intestine to engineer innervated muscle “sheets.” The sheets are then wrapped around tubular chitosan scaffolds. Chitosan is a natural biomaterial derived from shrimp shells. The material is already approved by the U.S. Food and Drug Administration for certain applications.

The tubular structures were implanted just under the skin of rats for 14 days, a first step in assessing their performance. Researchers found that the implants developed a blood vessel supply and that the tube opening was maintained. In addition, the innervated muscle “remodeled,” which means that the cells began the process of releasing their own materials to replace the scaffold.

“It is the combination of smooth muscle and neural cells in gut tissue that moves digested food material through the gastrointestinal tract and this has been a major challenge in efforts to build replacement tissue,” said Bitar. “Our preliminary results demonstrate that these cells maintained their function and the implant became vascularized, providing proof of concept that regenerating segments of the is achievable.”

The researchers’ next steps are to develop the lining of the intestine that is responsible for absorption and secretion. In a study involving research animals, they also plan to surgically connect the replacement segments to native intestine to assess function.

The group’s second project, to engineer anal sphincters, also reached a new milestone with the successful implantation of the structures in rabbits.

“These bioengineered sphincters, made with both muscle and nerve cells, restored fecal continence in the animals throughout the six-month follow-up period after implantation,” he said. “This provides proof of concept of the safety and efficacy of these constructs.”

Sphincters are ring-like muscles that maintain constriction of a body passage, such as controlling the release of urine and feces. There are actually two sphincters at the anus – one internal and one external. A large proportion of in humans is the result of a weakened internal sphincter.

“Many individuals find themselves withdrawing from their social lives and attempting to hide the problem from their families, friends and even their doctors,” said Bitar. “Many people suffer without little help.”

To engineer the internal anal sphincters, researchers used a small biopsy from the animals’ sphincter tissue and isolated that were then multiplied in the lab. In a ring-shaped mold, these cells were layered with nerve isolated from small intestine to build the sphincter. The mold was placed in an incubator, allowing for tissue formation. The entire process took about four to six weeks.

The bioengineered sphincters mimicked the architecture and function of native tissue and there are no signs of inflammation or infection after implantation. The constructs demonstrated the presence of contractile smooth muscle as well as mature nerve-cell populations.

“In essence, we have built a replacement sphincter that we hope can one day benefit human patients,” said Bitar. “Because these sphincters are made with both muscle and , they are ‘pre-wired’ to be connected with nerve pathways in the intestine.”

Bitar’s goal is to eventually conduct studies of the technology in humans. He said the technology could be applied to other diseases of the sphincter muscles, including urinary incontinence.

Age-reversal effects of ‘young blood’ molecule GDF-11 called into question

The leading theory for why the blood of younger mice rejuvenates the muscles of older mice is now in contest. The vampiric exchange of young blood and old blood has long been reported to have anti-aging effects, but it was in 2013 when Harvard University researchers first linked GDF-11, a molecule that circulates in the blood, to this effect.

Now, an analysis that set out to see how GDF-11 works in the muscles published May 19 in Cell Metabolism found just the opposite. The investigators showed first that GDF-11 was not specifically measured; the methods that were previously used were not specific for GDF-11, but also measured another molecule it closely resembles, called myostatin, which is well known to inhibit .

The new study, led by David Glass at the Novartis Institutes for BioMedical Research, in collaboration with Massachusetts General Hospital and the University of California, San Francisco, used tests to more accurately measure GDF-11 (short for Growth Differentiation Factor 11) in the blood of animals and humans and found that it showed hints of increasing with age, and clearly did not decrease with age. They also show that regularly injecting mice with pure GDF-11 causes to worsen, resembling effects seen in older age.

“This is a carefully conducted study that is certain to generate a vigorous discussion about what role GDF-11 plays, if any, in aging muscle,” says Se-Jin Lee, an expert on growth/differentiation factors and molecular biologist at Johns Hopkins University who did not participate in the research.

“I think that these new results definitely raise questions as to whether GDF-11 was really being exclusively detected in the prior paper,” Lee adds. “Clearly, these discrepancies will need to be resolved with additional studies, especially given the enormous effort being undertaken in the pharmaceutical community to target the myostatin pathway to treat muscle loss.”

Giving GDF-11 at doses previously used in aged animals did not improve regeneration, as previously claimed. When younger animals were treated with GDF-11, regeneration was worsened. The authors developed a test that could detect GDF-11 levels specifically and suggest that, for humans, testing for high levels of GDF-11 could potentially make them eligible for medicines that block GDF-11 activity.

“Clearly, like the mythical fountain of youth, GDF11 is not the long sought rejuvenation factor,” write Caroline Brun and Michael A. Rudnicki of the Ottawa Hospital Research Institute in a preview to the Cell Metabolism paper. They say, given these new findings, “the suggested ‘rejuvenating’ activity of GDF11 in the heart and brain should also be re-examined – since the underlying premise of those other two manuscripts, that GDF11 decreases with age, is contradicted by [the new] manuscript.”

Tuberculosis drug can improve effect of cognitive behavioral therapy

A new study from Sweden’s Karolinska Institutet shows that the effect of internet-based CBT (cognitive behavioural therapy) for people with people with obsessive-compulsive disorder (OCD) may be boosted with a drug called d-cycloserine, which has long been used to treat TB. According to the results, which are published in the journal JAMA Psychiatry, this enhancing effect is counteracted by antidepressants.

By Aidsmam.com

By Aidsmam.com

“These types of drugs are sometimes called cognitive enhancers, as they affect specific brain processes that can speed up and boost the effects of psychotherapy,” says Dr Christian Rück, psychiatrist and researcher, who conducted the study with his colleagues at Karolinska Institutet’s Department of Clinical Neuroscience. “You could say that it’s to CBT what spinach is to Popeye.”

The active therapeutic component of CBT is based on the concept of exposure or extinction, whereby the individual puts him/herself in feared situations that evoke feelings of discomfort or anxiety and remains there until the sensation wanes. D-cycloserine (DCS) is an old tuberculosis drug that also affects one of the brain’s most common receptors, the NMDA receptor. Previous studies have shown, for example, that DCS can amplify the effect of CBT if taken just prior to exposure to the fear-inducing stimulus.

In the present study, the researchers tried adding DCS to online CBT for people with OCD. Previous research had shown that DCS can speed up the therapeutic effect of CBT for this disorder, but no study had been large enough to demonstrate lasting effects once the therapy has finished. The study randomly assigned 128 people with an OCD diagnosis to either a DCS or a placebo group.

The initial analysis indicated that while there was no difference between DCS and placebo, the effect of online CBT was considerable. In their subsequent analysis, the team therefore took into account whether the participants were also taking antidepressants. Doing so, they found that those not on antidepressants responded much better to DCS.

“This tells us that the mechanism for DCS can be affected by antidepressants or vice versa and that it might one day be possible to use DCS and similar substances to boost the effect of CBT,” says Dr Rück. “Our study is the largest to date on DCS and OCD, but more research needs to be done to substantiate these positive effects and to fully understand and utilise the biological mechanisms behind effective CBT therapy.”

Source: Science Daily

Pactamycin analogs offer new, gentler approach to cancer treatment

Researchers at Oregon State University are pursuing a new concept in treatment of epithelial cancer, especially head and neck cancer, by using two promising “analogs” of an old compound that was once studied as a potent anti-tumor agent, but long ago abandoned because it was too toxic.


By Redorbit.com

The analogs are more highly selective than the parent compound, pactamycin, which originally was found to kill all cells, from bacteria to mammals, by inhibiting their protein synthesis.

The pactamycin analogs, which were developed with biosynthetic engineering, also offer a different approach toward cancer therapy — an effort to essentially put cancer cells to sleep, instead of killing them. If successful, this trend may herald a new future in “kinder and gentler” cancer treatments.

Findings on this promising approach to cancer were just published in PLOS One, in work supported by the National Institute of Health and other agencies.

The effects of the pactamycin analogs, called TM-025 and TM-026, were characterized in head and neck cancer cell lines, which cause the eighth most common cancer in the world. But they may have applications to a wider range of cancers, the researchers said, particularly melanoma.

“A traditional view of chemotherapy is that you try to completely kill cancer cells and destroy tumors,” said Arup Indra, an associate professor in the OSU College of Pharmacy and one of the lead authors on the study. “Sometimes this is effective, sometimes not as much. An alternative approach is to cause rapid cell aging and induce premature senescence, which we believe could become a new frontier in cancer drug development.”

A senescent cancer cell, Indra said, doesn’t usually die, but the growth of it and the larger tumor is slowed or stops, and it continues to live in a vegetative state, almost like being asleep. Such an approach can be an alternative way to control cancer without completely killing it, which may help reduce problems with resistance that can quickly develop to chemotherapeutic drugs. And it also avoids some of the most toxic and debilitating side effects of cancer chemotherapies, which are often caused by cell death.

The new findings showed that these analogs of pactamycin largely stopped cancer cell proliferation and growth, causing cells to age and lose their ability to divide and grow. These effects are partly mediated by tumor suppressor p53, which is frequently mutated in human cancers. They do not yet form the basis for a therapy, researchers said, because methods must still be perfected to get them more selectively into the cancer cells.

“With further research we hope to create a nontoxic nanocarrier that could provide targeted delivery of the TM-025 and TM-026 analogs specifically to cancer cells,” said Gitali Indra, an OSU assistant professor and also a lead and corresponding author on the study. “In some cases, such as oral cancer, it may also be possible to use topical treatments. But this approach should have significant promise if we can develop techniques to adequately target the cancer cells.”

Story Source: Science Daily

More than half of probiotics contain traces of gluten, study finds

First author Dr. Samantha Nazareth, a gastroenterologist at Columbia University Medical Center (CUMC) in New York, NY, and colleagues recently presented their findings at the Digestive Disease Week 2015 meeting in Washington, DC.

When a person with celiac disease eats gluten – a protein found in wheat, barley and rye – their immune system attacks the villi of the small intestine. When the villi are damaged, the body has difficulty absorbing nutrients.

It is estimated that around 1% of the US population – the equivalent to around 1 in 133 Americans – have celiac disease. Around 83% of people with the condition, however, are believed to be undiagnosed or misdiagnosed with other illnesses.

Celiac disease can present more than 300 symptoms, making it tricky to diagnose. Some people may experience diarrhea and abdominal pain or bloating, while others may experience fatigue and weight loss, among other symptoms.

At present, the only treatment for celiac disease is to follow a gluten-free diet, though some people with the condition turn to dietary supplements – particularly probiotics – believing the products will help alleviate symptoms.

According to Dr. Nazareth and colleagues, previous research has found that patients with celiac disease who use dietary supplements tend to have more symptoms than those who do not use them. As such, they set out to determine whether probiotics on sale in the US may be contaminated with gluten.

Two probiotics labeled gluten-free contained gluten at levels exceeding FDA standards

Using a sensitive detection technique known as liquid chromatography-mass spectrometry, the team tested 22 popular probiotics for traces of gluten – more than half of which were labeled “gluten-free.”

The team found that 12 (55%) of the probiotics contained traces of gluten. While the majority of these probiotics contained the protein at levels less than 20 parts per million – a level considered to be gluten-free by the US Food and Drug Administration (FDA) – four (18%) of them exceeded this level.

What is more, two of the probiotics that contained gluten at levels higher than 20 parts per million – exceeding FDA standards for gluten-free products – were labeled gluten-free.

Dr. Peter Green, professor of medicine and director of the Celiac Disease Center at CUMC, believes the findings are worrisome for patients with celiac disease:

“We have been following reports in the scientific literature and news media on inaccurate labeling of nutritional supplements, and it appears that labels claiming a product is gluten-free are not to be trusted, at least when it comes to probiotics. This is a potential hazard for our patients, and we are concerned.”

Study co-author Dr. Benjamin Lebwohl, assistant professor of medicine and epidemiology at the Celiac Disease Center, stresses that it is unclear as to whether the gluten in these probiotics may pose harm for patients with celiac disease at the levels identified.

“We know that most patients with celiac disease only develop intestinal damage when consuming more than 10 milligrams of gluten daily, and it is unlikely that contaminated probiotics can lead to that amount unless patients are ingesting mega-doses,” he explains.

He adds, however, that their findings are still a cause for concern. “Why is there any gluten in these products? Why should the consumer pay any attention to gluten-free labeling on such products? And given the great consumer interest in probiotics, will regulatory bodies take action to protect the public?”


Last week, Medical News Today reported on a study published in JAMA Neurology, in which researchers found people with celiac disease may be at higher risk of nerve damage.

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