Vaccino Sangamo ZFP

La sangamo il 14 alla conferesza degli investitori, pubblichera' un update per il vaccino basato su tecniche ZFP.
Lo studio e' attualmente in fase 2b.
Lo studio prevede una via per eradicare il virus:
Si Utilizzano cellule staminali , e grazie ad una tecnica detta "zinc finger" (dita di zinco) blocca le parti di dna che codificano per la porta ccr5 e le inietta nell'orgnismo.

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Sangamo BioSciences Announces Presentation at the 13th Annual BIO CEO & Investor Conference
Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today that Edward Lanphier, Sangamo's president and CEO, will provide an update on the progress of Sangamo's ZFP Therapeutic® development programs and an overview of the company's business strategy at 2:30 pm ET on Monday, February 14, 2011 at the 13th Annual BIO CEO & Investor Conference which will be held in New York City.


The presentation will be webcast live and may be accessed via a link on the Sangamo BioSciences website in the Investor Relations section [Devi essere iscritto e connesso per vedere questo link] under Events and Presentations. The presentation will be archived on the Sangamo website for two weeks after the event.

About Sangamo

Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for therapeutic gene regulation and modification. The most advanced ZFP Therapeutic® development program is currently in a Phase 2b clinical trial for evaluation of safety and clinical effect in patients with diabetic neuropathy and a Phase 2 trial in ALS. Sangamo also has a Phase 1/2 clinical trial and two ongoing Phase 1 clinical trials to evaluate safety and clinical effect of a treatment for HIV/AIDS as well as a Phase 1 trial of a treatment for recurrent glioblastoma multiforme. Other therapeutic development programs are focused on Parkinson's disease, monogenic diseases, neuropathic pain and nerve regeneration. Sangamo's core competencies enable the engineering of a class of DNA-binding proteins known as zinc finger DNA-binding proteins (ZFPs). By engineering ZFPs that recognize a specific DNA sequence Sangamo has created ZFP transcription factors (ZFP TFs) that can control gene expression and, consequently, cell function. Sangamo is also developing sequence-specific ZFP Nucleases (ZFNs) for gene modification. Sangamo has established strategic partnerships with companies in non-therapeutic applications of its technology including Dow AgroSciences and Sigma-Aldrich Corporation. For more information about Sangamo, visit the company's website at [Devi essere iscritto e connesso per vedere questo link]

ZFP Therapeutic® is a registered trademark of Sangamo BioSciences, Inc.

SOURCE Sangamo BioSciences, Inc.

Presentati al Croi 2011 i dati della sperimentazione del SB-728-T, si tratta di una Terapia Genica che blocca il recettore CCR5 dai Cd4.
Bloccando il recettore CCR5 dovrebbe essere impedito l'accesso al virus Hiv.
Uso il condizionale, in quanto il virus mutando potrebbe utilizzare anche un altra porta di accesso la CXCR4.
Il vaccino e' prodotto dalla Sangamo con la tecnica Zinc Finger (dita di zinco)

Traduco i passi salienti:

Finora, lo studio ha curato sei pazienti immuno-discordanti, la maggior parte dei quali vivono con l'HIV da almeno 20 anni e avevano CD4 tra 200 e 500, nonostante diversi anni di terapia ARV.

Tre pazienti hanno ricevuto trapianti di 10 miliardi di CD4, e tre hanno ricevuto trapianti di 20 miliardi di CD4. Una terza coorte , composta da altri tre pazienti, riceverà 30 miliardi CD4. E un quarto gruppo, composto da quattro persone HIV-positive che non risponde più virologica alla terapia ARV, è stato recentemente aggiunto allo studio.

Lalezari ha anche riferito che, dopo che le cellule trattate sono state espanse in laboratorio, circa il 26 per cento delle cellule trapiantate nel paziente sono stati modificati con successo.

Finora, il trapianto è stato ben tollerato. Non ci sono eventi avversi gravi sono stati riportati dopo che le cellule gene-modificato sono state infuse. Mentre ci sono stati diversi episodi di effetti collaterali legati ai farmaci, inclusi brividi, febbre, cefalea, sudorazione, vertigini, stanchezza e un breve odore di "aglio" sul corpo (probabilmente a causa di uno dei composti utilizzati per congelare le cellule prima del trapianto) -tutti gli eventi avversi sono stati di facile gestione. Inoltre, il gruppo Lalezari è documentato nessun anomalie di laboratorio.

Le cellule modificate sono state innestate con successo in tutti i pazienti e persisteva in cinque soggetti. Quattordici giorni dopo il trapianto, le cellule CD4 SB-728-T-trattati costituivano dal 1 per cento al 6 per cento delle cellule nel sangue di questi cinque pazienti, numero apprezzabile che rimase costante per tutta la durata dello studio. Questi cinque pazienti hanno anche avuto aumenti significativi nei loro guadagni di conta delle cellule CD4-media di 200 CD4, nelle settimane e nei mesi successivi alla loro trapianti.


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February 28, 2011

CCR5 Gene Therapy Shows HIV Treatment Potential
by Tim Horn


SB-728-T, a gene therapy designed to knock out the CCR5 receptor on CD4 cells, protects and increases CD4s in patients experiencing poor immunologic recovery while on antiretroviral (ARV) therapy, according to preliminary Phase I study data reported on Monday, February 28, at the 18th Conference on Retroviruses and Opportunistic Infections (CROI) in Boston. The new results, reported by Jay Lalezari, MD, are among the first from a human study illustrating the therapeutic—and curative—potential of this novel approach being developed by Sangamo BioSciences.

After HIV binds to the CD4 protein on T-cells, the virus must then latch onto another receptor on the cell's surface – either CCR5 or CXCR4. Earlier in the course of HIV disease, most people have HIV that uses the CCR5 receptor. Later on, as HIV disease progresses, the virus can switch to the CXCR4 receptor—this occurs in approximately 50 percent of treatment-experienced patients.

Selzentry (maraviroc), a U.S. Food and Drug Administration (FDA)-approved ARV, works by blocking the interaction between CCR5 and HIV, ultimately retarding the virus’s ability to infect CD4 cells. SB-728-T, a zinc finger DNA-binding protein transcription factor, goes one step further—it blocks the gene responsible for making CCR5, mimicking a naturally occurring human mutation that renders individuals largely resistant to the virus.

This mutation, dubbed CCR5 delta-32, appears to have no deleterious effect in the human body. In addition, a study published in Blood in December 2010 reported an effective cure when an HIV-positive patient with leukemia received a bone marrow transplant from a “matched” donor with this delta-32 CCR5 mutation.

Sangamo is also developing a gene therapy designed to knock out CXCR4, as highlighted in a separate presentation at CROI by Craig Wilen, a biomedical graduate student at the University of Pennsylvania. For individuals, SB-728-T is not likely to help; these people need a therapy that targets the gene responsible for creating CXCR4 receptors on CD4 cells.

Sangamo’s gene therapy approaches have both therapeutic and curative potential. At present, only Sangamo’s CCR5-knockout SB-728-T has entered clinical trials. The company is currently conducting two Phase I and one Phase I/II studies of SB-728-T, evaluating the safety and potential treatment efficacy in a wide range of patients, including those not yet on HIV treatment, those on treatment with undetectable viral loads but with poor CD4 cell responses, and those with drug-resistant HIV.

Therapy involves removing CD4 cells from patients’ blood, treating the cells with SB-728-T to knock out the CCR5 gene, expanding the cells in the lab, then transplanting the HIV-resistant genetically modified cells back into the body.

Curing HIV will be a bit more complicated, as it ultimately requires replacing the entire CD4 population with HIV-resistant cells, not merely creating a small reservoir of protected cells. A curative approach will likely involve removing and treating stem cells with CCR5 and possibly CXCR4 knockout genes, administering high-dose chemotherapy to wipe out the existing HIV-susceptible immune system, followed by transplanting the modified stem cells to rebuild an immune system that is resistant to the virus.

Paula Cannon, PhD, of the University of Southern California will be reviewing her group’s success with CCR5-depleted stem cells in mice with humanized immune systems during a Wednesday afternoon, March 2, session at CROI.

Lalezari reported preliminary results from his group’s Phase I study (SB-728-0902) involving HIV-positive patients with “immune-discordant” responses to ARV therapy—undetectable viral loads but limited CD4 gains despite several years of treatment. Thus far, the study has treated six immune-discordant patients, most of whom had been living with HIV for at least 20 years and had CD4s hovering between 200 and 500 despite several years of ARV therapy.

Three patients received transplants of 10 billion CD4s, and three received transplants of 20 billion CD4s. A third cohort, consisting of another three patients, will receive 30 billion CD4s. And a fourth cohort, made up of four HIV-positive individuals no longer responding virologically to ARV therapy, was recently added to the study.

Lalezari also reported that, after the treated cells were expanded in the lab, approximately 26 percent of the cells transplanted back into the patient were successfully modified.

Thus far, transplantation has been well tolerated. No serious adverse events were reported after the gene-modified cells were infused. While there were several incidences of drug-related side effects—including chills, fever, headache, sweats, dizziness, fatigue and a short-lived “garlic” body odor (likely due to one of the compounds used to freeze the cells before transplanting)—all adverse events were easily managed. In addition, Lalezari’s group documented no laboratory abnormalities.

The modified cells were successfully engrafted in all patients and persisted in five subjects. Fourteen days after the transplant, SB-728-T-treated CD4 cells made up 1 percent to 6 percent of the cells in the blood of these five patients, appreciable numbers that remained consistent throughout the duration of the study. These five patients also experienced significant increases in their CD4 cell counts—average gains of 200 CD4s were reported—in the weeks and months following their transplants.

In addition, five of the six subjects also exhibited sustained improvements in their CD4:CD8 cell ratio, an indicator of immunologic health that is infrequently documented in ARV therapy clinical trials.

The modified cells also took up residence in rectal tissue—a major reservoir of virus in the body—suggesting, as predicted, that the cells were remaining impervious to HIV infection and were continuing to expand.

"These data represent the beginning of a new hope for HIV therapy," said Lalezari. "This approach aims to provide a protected reservoir of HIV-resistant CD4 cells that are available to fight infections, including the virus. I look forward to completing the follow-up of this initial study and to working with Sangamo as it expands these studies to include the full range of HIV-infected populations."



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