Biomedical research

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Landmarks in gene therapy research

While gene therapy holds much promise, there have been a few unfortunate cases of serious adverse events, and these have had an inevitable effect on progress in this area. This page give a chronological overview of landmark events from drop-backs to successes in gene therapy research.

  1. April 2008: Success for inherited blindness
  2. November 2007: Adverse event arthritis study
  3. October 2007: Results for Parkinson’s disease
  4. October 2006: Results for Parkinson’s disease
  5. September 2006: Partial success for melanoma
  6. April 2006: Partial success for CGD
  7. 2003 – 2004: Chinese Gendicine for head and neck cancer
  8. 2000 – 2005: Leukaemia but also success in X-linked SCID
  9. 1999: The Jesse Gelsinger case


 

1. April 2008: Success for inherited blindness

Results of world's first gene therapy for inherited blindness show sight improvement. UK researchers from the UCL Institute of Ophthalmology and Moorfields Eye Hospital NIHR Biomedical Research Centre announced results from the world’s first clinical trial to test a revolutionary gene therapy treatment for a type of inherited blindness.
The results, published in the New England Journal of Medicine, show that the experimental treatment is safe and can improve sight. The findings are a landmark for gene therapy technology and could have a significant impact on future treatments for eye disease. See Press release.

 

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2. November 2007: Adverse event inflammatory arthritis study

An adverse event led to a clinical trial hold in July 2007. The U.S. Food and Drug Administration (FDA) removed the hold following the agency's review of the safety data on all 127 subjects and all data from a fatal serious adverse event.

Gene medicine found safe
The data obtained during the investigation indicated that the investigated gene medicine did not contribute to the patient's death, which was due to a fungal infection (histoplasmosis). The subject was on other medications as well, which were known to be immunosuppressive and a risk factor for histoplasma infection.

 

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3. October 2007: Results for Parkinson’s disease

On October 17, American researchers reported successful results from a phase I gene therapy trial for Parkinson’s disease. In the trial 12 patients had gene medicine infused into a specific part of their brains.

Towards a phase 2 Trial
At the time of the announcement, 3 years after treatment, the first patient was dramatically improved, and 9 of the other patients showed on average 37% improvement. The company developing this therapy, together with its partners, are now working towards a phase 2 randomized controlled trial.

 

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4. October 2006: Results for Parkinson’s disease

In October 2006, there were two promising announcements of success in treating Parkinson’s disease by gene therapy in phase I trials.
On October 16, the organizations involved announced that CERE-120, a gene therapy product they are developing for Parkinson’s disease, was well tolerated and appeared to reduce symptoms by approximately 40% in a phase 1 study with 12 patients with advanced disease.
The companies are planning a phase 2 randomized controlled trial involving approximately 50 patients.

 

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5. September 2006: Partial success for metastatic skin cancer (melanoma)

Much excitement was caused by the report of successful immunotherapy treatment of two patients with metastatic melanoma in September 2006. Researchers were able to engineer tumor recognition in the patients own immune cells.
For up to one year, this resulted in the retreat of metastatic melanoma lesions in two patients; a dramatic improvement for patients who had only been expected to live for 3 to 6 months. However 15 other patients did not respond to the treatment. Further work is underway to improve response rates and refine the approach.

 

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6. April 2006: Partial success for Chronic granulomatous disease (CGD)

In April 2006 one of two patients died from a severe bacterial infection two years after an experimental gene therapy treatment. It appears that the patient’s death was not due to a side effect of the gene therapy treatment, rather to a return over time of the CGD symptoms she was successfully treated for two years earlier.
In this trial, precursor immune cells from the patients blood were genetically altered in the laboratory and given back to the patient. The team behind the trial is currently investigating the reason for the loss of correction of the disease.

 

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7. 2003- 2004 Chinese Gendicine for head and neck cancer

Gendicine, a gene medicine developed as a treatment of cancer, was approved for clinical use by the Chinese State Food and Drug Administration in October 2003.

This was followed by a license for its commercial production in spring 2004; however, this went ahead without data from a standard phase III trial, and it seems that the approval was made on the basis of tumor shrinkage, rather than extension of patient lifetime. There has been quite some concern from gene therapy researchers elsewhere in the world as to the quality of the trials performed and thereby the safety and efficacy of the treatment.

To date, the phase I and phase II trial results in patients with head and neck squamous cancers have only been published in Chinese language medical journals; the only English language article on the trials is a review summarizing the data, the value of which has since been questioned by several groups.

Despite these concerns, some patients have flown to China to try it, and the company stated in December 2006 that they had treated more than 4000 patients with Gendicine.

 

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8. 2000 – 2005: Leukaemia but also success in X-linked SCID

In 2000 the morale of the gene therapy community was lifted with the first report from France of successful treatment of children suffering from a rare, lethal immune disease named X-linked severe combined immunodeficiency (SCID-X1).

The excitement gave way to alarm at the end of 2002, when two of the ten children developed a leukaemia-like symptoms. It appeared that the gene therapy procedure resulted in an increased risk tot develop leukaemia.

These first two serious adverse events fuelled a global debate over the future of gene therapy and led investigators and gene therapy societies in Europe and the USA to critically examine the risk/benefit ratio of gene therapy.

The trial was voluntarily halted while the cause of these conditions was investigated and the patients were treated for them. An ongoing UK trial using a similar approach but with a different protocol to treat SCID-X1 was allowed to continue and went on to achieve successful results, as did the treatment of a SCID-X1 child in a similar trial in Australia.

The French trial was restarted with a revised protocol using lower doses of modified cells. In January 2005 a third child developed a leukaemia-like symptoms, involving a different genetic basis; this patient and one of the earlier two patients responded well to chemotherapy treatment and are in complete remission.

Sadly, one of the three affected patients did not respond to the chemotherapy treatment for the leukaemia-like condition and died in October 2004; however, all of the other patients in the French trial have benefited from the gene therapy, with correction of their otherwise lethal immunodeficiency extending beyond 6 years for the first patients treated.

 

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9. 1999: The Jesse Gelsinger case

The first case in which a gene therapy treatment turned out wrong, involved the death of 18-year-old Jesse Gelsinger on September 17, 1999. Jesse was treated for a rare metabolic disorder. His death was attributed to an inflammatory reaction to one of the components used in the experimental therapy.


In January 2000, the US Food and Drug Administration (FDA) put a hold on the trial and several other trials were also halted. In its final judgment on the case in February 2005 the US Department of Justice held the University of Pennsylvania responsible, ordered them to pay a $517.000 settlement, and placed research restrictions on the doctors who conducted the trials.
The doctors did not stick to the protocols of the study and withheld information about side-effects in previous studies. This was widely seen as a major blow for the gene therapy community.

 

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