With still no gene therapy drug approved by the FDA, and only one controversial product in the market (Gendicine, approved only in China) since 2004, gene therapy is very much in its experimental stages.

And yet, the global market for gene therapy is already projected to reach $484 million by 2015. There is quite a huge revenue to be made, but still way below the estimates when Gendicine first came out. Market predictions depend on the approval of products, cost of treatment and the population that the drugs target but progress has been slow until this year. In May 2008, Phase III trial for end-stage head and neck cancer, the first for cancer, showed marked improvements in patient survival. In April and later in October, six patients with inherited blindness reported better vision when treated using an adeno-associated virus delivered directly to the eyes.

Currently, many other cancer and cardiovascular diseases are already in Phase III/Phase II of clinical trials, so there is promise in the horizon.

Image credit: Newscom

A new study found that premature ejaculation is not purely psychological. Genetics has a lot to do with it.

Scientists from Utrecht University in the Netherlands studied 89 Dutch men who had "primary premature ejaculation", which means they suffered from it from their first sexual contact. They were compared with 92 men who had no such history. In men with premature ejaculation, the serotonin was deficient in the area of the brain that controls ejaculation.

Serotonin is a neurotransmitter that controls body temperature, sleep, sexual activity, appetite and emotions such as anger, aggression and mood. A common polymorphism (5HTTLPR) within the promoter region of the serotonin transporter gene has been shown to influence the amount and activity of serotonin, so the authors postulate that 5HTTLPR may control the rapidity of ejaculation. In the study, men who had the LL genotype of 5HTTLPR ejaculated twice as rapidly as those who had the alternate genotype (SS) or were heterozygous (SL).

The take home message: The research contradicts the common idea that the primary form of premature ejaculation is a psychological disorder. With further study and confirmation, the authors hope gene therapy against premature ejaculation would be possible in the future.

The study will be published online this week in the Journal of Sexual Medicine.

via Science Daily

P52 gene, arrows show locations of common mutations 

(Image courtesy www.bioinf.org)

Following on from my last article on using gene therapy for increasing survival in head and neck cancer, Professor Jack Roth, M.D., professor in M. D. Anderson’s Department of Thoracic & Cardiovascular Surgery and colleagues are now focusing on ways to deliver p53 and other tumor-suppressing genes systemically - through intravenous delivery.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself.

Advexin has to be injected straight into the tumor, but that’s not workable for many cancers. Head and neck cancer kills patients by recurring, not spreading to other organs, but most cancer deaths involve metastasis.

By wrapping tumor-suppressing genes in tiny balls of fat, Roth and colleagues hope to be able to treat more invasive cancers. While p53 nanoparticles are still in preclinical development, those that deliver another tumor-suppressor called FUS1 are in a phase I clinical trial for non-small cell lung cancer. Through 19 patients, the dose escalation study has yet to encounter significant side effects.

Injected nanoparticles gather mainly in tumors, where they are taken up and dissolved, leaving the tumor-suppressor gene at work in the cell. A version that combines FUS1 and p53 is under development.

Elaine Warburton  www.geneticsandhealth.com

Thank you to Jennifer Texada at MD Anderson for bringing this great cancer treatment discovery to my attention….

(Image courtesy Introgen Therapeutics)

A gene therapy invented at The University of Texas M. D. Anderson Cancer Center is the first to succeed in a U.S. phase III clinical trial for cancer.  Introgen Therapeutics, Inc a spin out from MD Anderson, reported results of its phase III trial of Advexin, a modified adenovirus that expresses the tumor-suppressing gene p53, for end-stage head and neck cancer.

The p53 gene is inactivated in many types of cancer. Its normal role is to halt the division of a defective cell and then force the cell to kill itself.

“Cells become cancerous because p53 no longer functions. Restoring p53 works unlike any current cancer treatment because it treats the cancer genome,”said Jack Roth, M.D., professor in M. D. Anderson’s Department of Thoracic & Cardiovascular Surgery, who invented the drug and co-founded Introgen.

The trial showed that p53 expression in the patient’s tumor before treatment is a reliable biomarker for how to treat head and neck cancer. Patients with a favorable p53 profile who received Advexin had an average survival of just over 7 months, compared with just under 3 months for those whose tumor expressed high levels of mutant p53 before treatment. Patients with this unfavorable profile were better off taking the chemotherapy drug methotrexate, resulting in n average survival of just under 6 months.

“The important finding is that patients who benefit from treatment can be identified with the p53 biomarker. The biomarker will enable physicians to personalize treatment,” said Roth.

Better Quality of Life

Patients treated with Advexin experienced far fewer harmful side effects such as pneumonia than those who received methotrexate. The incidence of inflammation of the mouth lining and a decrease in white blood cells, for example, both dropped to zero for those receiving Advexin.

“That certainly results in a better quality of life,” Roth noted, which makes sense because p53 does not cause problems in normal cells.

Roth’s lab has been developing gene therapy for cancer since 1990. “We wanted to go beyond conventional treatment, because most of those treatments were not very effective,” Roth said. “Surgery and radiation are limited to the local tumor and once given, it’s very hard to repeat those therapies.  Chemotherapy inhibits DNA replication, but it also interferes with normal cells.”

Elaine Warburton  www.geneticsandhealth.com

Maxi-K gene therapy may be a safe and effective future option for men whose erectile dysfunction (ED) is not treatable with oral therapy. This therapy is not yet available commercially but shows immense promise for the future.

Maxi-K therapy is a unique, locally administrated gene-transfer technology to treat erectile dysfunction (ED). The safety and the restorative effects of the treatment have been shown by data from participants in a phase I trial. In some men, the effect lasted up to six months.

The gene therapy appears safe as no transfer-related adverse events were reported more than two years after the transfer in some subjects. Unlike conventional oral treatments for men with ED, Maxi-K therapy doesn’t require prior planning, fosters sexual spontaneity and can be used by men taking heart medication.

Elaine Warburton  www.geneticsandhealth.com

A new paper in Nature Reviews Genetics, entitled “Genetic Medicines: Treatment Strategies for Hereditary Disorders,” discusses potential genetic therapy for inherited diseases caused by a defect in one gene. (Not multifactorial diseases, such as cardiovascular disease, that are caused by a complex interaction of multiple genes and environmental factors.)

Genetic therapy techhniques discussed:

• Gene transfer using viral vectors, e.g., adenoviruses and retroviruses.
• RNA-modification therapies - suppressing or stimulating RNA that is the intermediate step between DNA and protein.
• Embryonic stem cells for regenerating organs, etc.

Dr. Timothy O’Connor, Assistant Research Professor of Genetic Medicine at Weill Cornell:

Remember, drug development is always a 10-to-15-year process, whatever the theory behind it. And just in the last decade we’ve seen enormous leaps forward, such as faster high-throughput screens, hapmap technologies and other advances. It’s our belief that even more astonishing advances are yet to come that will turn the dream of genetic medicine into a reality for patients at the bedside.

Not just at the bedside, but hopefully before. Preventive medicine is far more effective than medicine after people have fallen ill.

Medical News Today, April 3, 2006