Navigation Links
Gene therapy advance treats hemophilia in mouse models

Vector improved in two ways creates a sustained, partial correction to bleeding problems in mice

A virus that typically infects insects could help with the development of gene therapy treatment for Hemophilia A, a condition in which even a bump on the knee can cause serious internal bleeding in people.

Researchers at the University of Iowa Roy J. and Lucille A. Carver College of Medicine improved a vector -- a vehicle that delivers gene therapy to cells -- in two ways to create a sustained, partial correction to bleeding problems in mice engineered to have Hemophilia A, which is also known as factor VIII deficiency. The findings appear in the Sept. 1 issue of the journal Blood (published Aug. 19 online).

The team adapted the outer layer, or "coat," from a baculovirus, a virus that infects butterflies and moths, onto another modified virus. This hybrid vehicle could more easily attach to certain liver cells and allow the genes within the vehicle to enter the cells. The genes then caused the liver cells to make the protein that prevents bleeding.

The researchers also modified the vehicle so that it would express these therapeutic genes only in liver cells, thus reducing the likelihood of negative side effects.

The laboratory findings have significant potential for developing improved treatment for hemophilia but are not yet applicable to people, cautioned Paul McCray, UI professor of pediatrics and the study's corresponding author. "It's an exciting finding, but we are still many steps away from a possible gene therapy for people with hemophilia," he said.

Hemophilia A is the leading sex-linked bleeding disorder, affecting one in 5,000 to 10,000 males. People with the condition have a genetic mutation that leaves them with little to no factor VIII protein to prevent uncontrolled bleeding. Individuals with the severe form of the disease have less than 1 percent of the normal amount of protein. However, only a rela tively small amount of the normal protein level is needed to make the problem milder and, thus, less life threatening.

"Hemophilia is considered an ideal candidate for correction with gene therapy because if you could just raise the factor VIII activity from less than 1 percent of normal to within 5 to 10 percent of normal, the tendency for spontaneous bleeding and need for hospitalization would diminish dramatically," McCray said.

"In the mouse model in our study, we were able to achieve levels of gene expression that converted the hemophilia A in the mouse from a severe to a mild form. The correction lasted 30 weeks -- the duration of the study," he added.

One of the current treatments for hemophilia involves intravenously delivering recombinant (genetically engineered) human factor VIII protein to prevent bleeding episodes. However, the weekly to bi-weekly preventive treatments are extremely expensive, costing up to $500,000 per year. In addition, over time some patients may develop antibodies to the protein, making the treatments less effective.

In earlier studies, McCray's team, which includes Yubin Kang, M.D., at the time a UI assistant research scientist in pediatrics (now a UI resident in internal medicine), targeted the liver because its main functional cells, called hepatocytes, can make the factor VIII protein and secrete it into the bloodstream. However, the investigators recognized the need to target the liver more effectively.

"It has been difficult to conclusively identify the cells that normally make factor VIII," McCray said. "Hepatocytes may not be the main source of this protein, but they are relatively easy to target. So we aimed to find a way to get these cells to make more of it. In effect, we're using the hepatocytes as a factory to make this protein and secrete it into the bloodstream."

To better target the hepatocytes in the mice, the team took the disabled protein coat from the baculovirus A utographa californica and put it on to a modified type of lentivirus called feline immunodeficiency virus (FIV). FIV causes leukemia in cats but no disease in humans.

The hybrid vehicle efficiently bound to receptors on the liver cells because the modified baculovirus coat serves as a "key" that fits into the "lock," or receptor. The percentage of liver cells that took up the virus increased from approximately 5 percent to 20 percent.

The team also modified the part of the FIV that expresses the therapeutic gene so that its promoter that causes gene expression worked only when it was in a liver cell.

"Even if this FIV modified virus goes to other organs of the body, it won't express well because its promoter is liver-specific," McCray said. "This modification helps prevent negative side effects. For example, if the gene were expressed in immune cells instead of liver cells, it could lead to a damaging immune response."

McCray said the team now is studying additional ways to make the hybrid vector express the protein even better.


'"/>

Source:University of Iowa


Related biology news :

1. Adding Radiation Therapy To Chemotherapy Improves Survival In Patients With High-risk Breast Cancer
2. Columbia research lifts major hurdle to gene therapy for cancer
3. Combination therapy boosts effectiveness of telomere-directed cancer cell death
4. Gene therapy converts dead bone graft to new, living tissue
5. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
6. New imaging method gives early indication if brain cancer therapy is effective, U-M study shows
7. Muscle-targeted gene therapy reverses rare muscular dystrophy in mice
8. New therapy for HIV/AIDS eliminates needles and excessive toxicity
9. New Treatment Rivals Chemotherapy For Lymphoma, Study Finds
10. Gene therapy for Parkinsons disease moves forward in animals
11. Pulsating ultrasound enhances gene therapy for tumors
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:5/9/2016)... -- Elevay is currently known as the ... high net worth professionals seeking travel for work   ... there is still no substitute for a face-to-face meeting. ... deal with a firm handshake. This is why wealthy ... citizenship via investment programs like those offered by the ...
(Date:4/26/2016)... DUBLIN , April 27, 2016 ... of the  "Global Multi-modal Biometrics Market 2016-2020"  report ... ) , The analysts forecast ... a CAGR of 15.49% during the period 2016-2020.  ... a number of sectors such as the healthcare, ...
(Date:4/13/2016)... April 13, 2016  IMPOWER physicians supporting Medicaid patients ... a new clinical standard in telehealth thanks to a ... the higi platform, IMPOWER patients can routinely track key ... body mass index, and, when they opt in, share ... visit to a local retail location at no cost. ...
Breaking Biology News(10 mins):
(Date:5/20/2016)... ... ... The leading Regenerative Veterinary Medicine Company, VetStem Biopharma ., is proud ... of their own patients with the VetStem Cell Therapy. Each of these veterinarians has ... patients. , The veterinarians are Dr Ross Rich former owner of Cave Creek ...
(Date:5/19/2016)... ... ... Anton Paar USA, located in Ashland, Virginia is pleased to announce that construction ... a third office building to the current facilities. , Growth is nothing new. ... with office space adjacent to the previous main building. Through remodels and new construction, ...
(Date:5/19/2016)... DIEGO , May 19, 2016 ... (OTC PINK: RGBP) and (OTC PINK: RGBPP) announced today ... creating the first cord blood based cancer immunotherapeutic ... provisional patent application, Regen described a generation of ... was potentiated by gene silencing.  The product in ...
(Date:5/18/2016)... , May 18, 2016 The Biotech ... does not mean that there are no opportunities ahead. Today, ... Inc. (NASDAQ: THLD ), Seattle Genetics Inc. (NASDAQ: ... ), and Ophthotech Corp. (NASDAQ: OPHT ). Sign ... at: http://www.activewallst.com/ Threshold Pharmaceuticals ...
Breaking Biology Technology: