Navigation Links
Gene Therapy Shows Promise Against Hereditary Lung Disease

An experimental gene therapy to combat alpha-1 antitrypsin deficiency, a common hereditary disorder that causes lung and liver disease, has caused no harmful effects in// patients and shows signs of being effective, University of Florida researchers say.

In a clinical trial, researchers evaluated the safety of using a so-called gene vector - in this case an adeno-associated virus - to deliver a corrective gene to 12 patients who are unable to produce a protein essential for health called alpha-1 antitrypsin.

“The primary end point in the trial was to see whether it was safe to give patients this gene transfer vector and then to try to begin to see if we could get the dose into a range where we would begin to replace the missing protein in the blood,” said Terence Flotte, M.D., a pediatrician, geneticist and microbiologist with UF’s College of Medicine and a member of the Powell Gene Therapy Center and the UF Genetics Institute. “We found that we can use this agent safely and we also saw evidence in the patients’ blood that the higher doses successfully introduced the vector DNA. In one patient we saw evidence for a very brief period that some of the alpha-1 protein was being produced, but not at a high enough level to be beneficial.”

The findings appear online today (Nov. 21) in the journal Human Gene Therapy.

Physicians injected doses of the virus containing copies of the gene for alpha-1 antitrypsin into the patients’ upper arms. Essentially, the virus is intended to “infect” patients’ cells with replacement genes that will do the necessary work to produce alpha-1 protein. UF scientists have successfully developed the technique in animal models.

The next step is to test the therapy with a different version of the adeno-associated virus; about 200 variations of the virus exist in nature.

“We have another version of the virus that appears in animal studies to be close to a thousandfold more pot ent at making protein,” Flotte said. “That’s very encouraging to us. So the next trial, which has already begun, is to use the new version of the virus and take patients through a similar range of doses, in a very similar scheme, and see if we can maintain the safety while pumping up the efficiency of the protein production.”

In most people, alpha-1 antitrypsin is made in the liver and protects the lungs by counteracting inflammatory products that destroy lung tissue. But about 100,000 Americans have alpha-1 antitrypsin deficiency, according to the Miami-based Alpha-1 Foundation, a national not-for-profit organization devoted to finding a cure. In addition, medical authorities suspect less than 5 percent of affected individuals are diagnosed, often not until they are in their mid- to late-30s, after extensive lung damage occurs. Shortness of breath, wheezing, chronic cough and recurring chest colds are signs of the disease.

It is important that alpha-1 patients avoid cigarette smoke, said Mark Brantly, M.D., a professor of medicine and molecular genetics and microbiology at UF’s College of Medicine who develops clinical research programs aimed at developing therapies for alpha-1 patients. Alpha-1 deficiency can in some patients lead to emphysema and cirrhosis, both progressive diseases that can be fatal.

Alpha-1 patients with symptoms of emphysema can be treated through weekly intravenous injections of alpha-1 protein derived from human plasma. The injections must continue throughout a patient’s life, according to the American Lung Association. It does not cure, but it does appear to slow the progression of this disease.

Patients in the clinical trial - 10 men and two women who ranged from 42 to 69 - were asked to discontinue their replacement therapy 28 days before receiving the gene therapy.

One volunteer who had not been on protein replacement therapy exhibited low-level expression of alpha-1 antitrypsi n, which was detectable 30 days after receiving an injection. However, residual levels of alpha-1 antitrypsin from the replacement therapy in the other patients obscured whether the alpha-1 gene had begun to express protein.

“As the authors conclude, the results set up the more interesting approach of using other AAV serotypes more suited for muscle delivery as an alternative with the same transgene in the next trial,” said Richard J. Samulski, a professor of pharmacology and director of the University of North Carolina’s Gene Therapy Center. “These studies are important milestones that allow the potential for gene correction of AAT to advance, as well as the (gene therapy) field in general. They also represent the step-by-step process established by the FDA and research community to ensure that safe and good clinical studies are employed in these early days, and I applaud Terry Flotte and his group for being cautious and thorough in their clinical design.”

Surce-Newswise
SRM
'"/>




Related medicine news :

1. Cancer Doctors Okays Controversial Prostate Therapy
2. Consensus on "Combination Therapy" for Breast Cancer
3. Gene Therapy shows promise in treating Hemophilia
4. "Make AIDS Therapy affordable" - Physicians demand
5. Hormone replacement Therapy a headache
6. Simple Therapy
7. Therapy for stopping the spread of cancer cells
8. Gene Therapy Destroys Pancreatic Cancer Cells
9. Letrozole Beats Tamoxifen in Breast Cancer Therapy
10. Garlic Supplements Impede HIV Therapy
11. Gene Therapy For Cystic Fibrosis
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:2/12/2016)... ... February 12, 2016 , ... A lot has been reported about ... president has access to health and wellness resources most Americans could ever dream of ... individual has a schedule as frenetic as the U.S. President. , In honor ...
(Date:2/12/2016)... (PRWEB) , ... February 12, 2016 , ... Basketball is ... and integral part of the Peety PoppersTM series, sign language translation is featured in ... of health and wellness in Peety PoppersTM lessons has a sign language translator to ...
(Date:2/11/2016)... ... ... “ HEALING MIND : Five Steps to Ultimate Healing, Four Rooms ... teaches readers how to become their own therapist. Providing a useful step-by-step process for ... offers an understanding of how to heal one’s inner child using four archetypes of ...
(Date:2/11/2016)... , ... February 11, 2016 , ... ... performing a wide range of cosmetic procedures. Along with performing procedures, the magazine ... and results of many cosmetic procedures. One of the most common procedures he ...
(Date:2/11/2016)... ... February 11, 2016 , ... The Chartis Group, ... top five firms in the “2015/2016 Best in KLAS: Software and Services” report ... is a research and insights firm on a global mission to improve healthcare ...
Breaking Medicine News(10 mins):
(Date:2/11/2016)... , Feb. 11, 2016 ... commonly used in laboratories. These may range from microscope ... Laboratory glassware is made from borosilicate glass because of ... plasticware, on the other hand, started gaining popularity over ... was easier to replace glass with plastic in several ...
(Date:2/11/2016)... 2016  Governor Andrew M. Cuomo today announced a ... throughout Western New York . This ... Polytechnic Institute, includes a major expansion of Athenex,s North ... Buffalo , as well as the creation of ... Dunkirk . The combined projects are expected ...
(Date:2/11/2016)... -- NOIT™ Research LLC, a private, leading-edge autism research group, ... assist needy families in obtaining one of its special ... 10, 2016 and March 31, 2016, the company will ... is an auditory stimulus that plays a key role ... Beth Shier , NOIT Research director. "The ...
Breaking Medicine Technology: