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.
|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|
|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|
|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|
|AV201||Avigin||AVGN||severe Parkinson’s disease|
|Theratope Vaccine||Biomira||BIOM||colorectal, metastatic breast cancer|
|BLP25 Liposome Vaccine||Biomira||BIOM||Prostate, non-small cell lung cancer|
|Clofarabine (CLOLAR)||Bioenvision||BIVN||pediatric acute lymphoblastic leukemia, solid Tumors|
|Velostan||Bioenvision||BIVN||post-menopausal advanced breast cancer,bladder cancer|
|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|
|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|
|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|
|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)|
|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|
|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|
|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|
|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|
|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 neurotransmitter —GABA|
|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|
|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|
|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|
|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|
|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|
|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|
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
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 red blood cells 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 proteinexport in Plasmodium may also have an additional function in small-molecule transport,” Gold says.
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 host cell 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 deadlymalaria 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 parasites.”
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 smooth muscleand 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 thegastrointestinal tract 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 fecal incontinence 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 smooth muscle cells that were then multiplied in the lab. In a ring-shaped mold, these cells were layered with nerve cells 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 nerve cells, 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.
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 muscle growth.
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 muscle repair 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.”
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.
“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
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.
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
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.
Written by Honor Whiteman