Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New genes at work in patients with hereditary lung disease

13.08.2009
Gene therapy trial succeeds in spurring production of a protective protein

Researchers at the University of Massachusetts Medical School and the University of Florida in Gainesville have safely given new, functional genes to patients with a hereditary defect that can lead to fatal lung and liver diseases, according to clinical trial findings slated to appear this week in the online early edition of the Proceedings of the National Academy of Science.

"This trial represents a very important step toward a potential gene therapy for the 100,000 or more Americans who suffer with alpha-1 antitrypsin deficiency," said Terence R. Flotte, MD, dean of the School of Medicine and provost & executive deputy chancellor of UMass Medical School. Dr. Flotte, senior author on the study, was formerly the chair of pediatrics at the University of Florida, where the study was conducted.

Patients with alpha-1 antitrypsin deficiency cannot produce a protective form of the protein alpha-1 antitrypsin, which is normally produced in the liver and protects the lungs from inflammation. Those lacking alpha-1 antitrypsin are vulnerable to infections or irritants in the air, such as cigarette smoke, and often develop life-threatening lung disease. Some people with the deficiency lead disease-free lives, never knowing they have defective genes. In others, the deficiency can lead to emphysema and cirrhosis, both progressive diseases that can be fatal.

In the clinical trial, three patients who received injections of a harmless virus containing copies of a correct gene for alpha-1 protein in their upper arms were able to produce trace amounts of alpha-1 antitrypsin for up to one year. Although the levels produced were not considered therapeutic, the study provided critical "proof of principle" that a corrected, functioning gene could trigger production of the protein. The National Heart, Lung and Blood Institute recently awarded a five-year, $2 million grant to Dr. Flotte for further clinical trials studying the use of an adeno-associated virus to deliver the alpha-1 antitrypsin gene.

"When you deliver this therapy into the deltoid muscles of the arm, the muscle becomes a factory for making the protein that these individuals are missing," said Mark L. Brantly, MD, a professor of medicine and molecular genetics and microbiology at UF's College of Medicine and first author of the study.

The trial established the safety of the adeno-associated virus used to "infect" patients' cells with replacement genes, which then do the vital work of producing the alpha-1 protein. Nine patients were divided in three groups to receive the gene therapy at the General Clinical Research Center at Shands at UF Medical Center. Patients received nine injections in their non-dominant upper arms, with the dosage increasing in each group. At 365 days after the injections, the transferred genes were measurably producing alpha-1 protein in the three patients who received the highest dose, showing that the normal gene was successfully transferred and had begun doing its intended job in the patients' muscles.

"I hope the alpha-1 community is as encouraged as I am that although this trial does not give us any guarantee, there is a fighting chance to develop a therapy using this method," said Dr. Flotte. "In patients receiving the highest dose in this study, we saw transgene expression. And although it approached just 1 percent of what we ultimately want, we can be reasonably optimistic that we can achieve much closer to normal values in people by using the same approach with an increased dose."

Although patients showed some elevated immune response to the gene therapy vector — which is designed to quickly break down after delivering its cargo — researchers did not detect any evidence that the patients' bodies rejected the transferred genes or the newly created protein.

"That's a really good sign," said Brantly, a member of the Powell Gene Therapy Center and the UF Genetics Institute, who sees about 150 alpha-1 patients in his medical practice. "After we gave the injections, the individuals stayed on the ward for five days while we monitored them. There were no ill effects, only a minimal amount of redness, and by the end of the five days most of the subjects were actually bored."

Currently, the only limitedly effective treatment for patients with serious breathing symptoms involves 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. They do not cure the disease, but they do appear to slow its progression.

"This study gives us encouraging evidence that gene therapy for alpha-1 is a realistic possibility," said John Walsh, president and chief executive officer of the nonprofit Alpha-1 Foundation, which has been supporting research of this kind for more than a decade. "The augmentation therapy available now has slowed down the progression of our lung disease and extended many of our lives. The hope of gene therapy is that we may have a one-time, brief series of injections that could allow our own bodies to produce the alpha-1 protein we need to live a normal lifetime. The alpha-1 community is incredibly grateful for the progress that these dedicated investigators have made," Walsh said.

The study was funded by grants from the National Heart, Lung and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, UF, the National Center for Research Resources, the Alpha-1 Foundation and from the study sponsor, Applied Genetic Technologies Corp., or AGTC, a company formed by UF researchers to develop gene therapies. UF holds an equity interest in AGTC. Brantly is the Alpha-1 Foundation Research Professor at UF and is a consultant for the organization.

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $200 million in research funding annually, 80 percent of which comes from federal funding sources. The work of UMMS researcher Craig Mello, PhD, an investigator of the prestigious Howard Hughes Medical Institute (HHMI), and his colleague Andrew Fire, PhD, then of the Carnegie Institution of Washington, toward the discovery of RNA interference was awarded the 2006 Nobel Prize in Physiology or Medicine and has spawned a new and promising field of research, the global impact of which may prove astounding. The mission of the University of Massachusetts Medical School is to advance the health and well-being of the people of the Commonwealth and the world through pioneering education, research, public service and health care delivery with our clinical partner, UMass Memorial Health Care.

Jim Fessenden | EurekAlert!
Further information:
http://www.umassmed.edu

More articles from Life Sciences:

nachricht Toward a 'smart' patch that automatically delivers insulin when needed
18.01.2017 | American Chemical Society

nachricht 127 at one blow...
18.01.2017 | Stiftung Zoologisches Forschungsmuseum Alexander Koenig, Leibniz-Institut für Biodiversität der Tiere

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: How gut bacteria can make us ill

HZI researchers decipher infection mechanisms of Yersinia and immune responses of the host

Yersiniae cause severe intestinal infections. Studies using Yersinia pseudotuberculosis as a model organism aim to elucidate the infection mechanisms of these...

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

A big nano boost for solar cells

18.01.2017 | Power and Electrical Engineering

Glass's off-kilter harmonies

18.01.2017 | Materials Sciences

Toward a 'smart' patch that automatically delivers insulin when needed

18.01.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>