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This is great news!
Kathleen
2009/8/28 [log in to unmask] <[log in to unmask]>
> This was one of the last missing parts to the puzzle - how to turn off gene
> therapy, if needed,
> Subject: off switch for gene therapy
> Date: Sat, 29 Aug 2009 01:02:12 GMT
> Public release date: 28-Aug-2009
> From EurekaAlert
>
> Contact: John Pastor
> [log in to unmask]
> 352-273-5815
> University of Florida
>
> UF scientists construct 'off switch' for Parkinson therapyCommon drug shuts
> down gene therapy in rats, addressing safety concerns for humansGAINESVILLE
> — A common antibiotic can function as an "off switch" for a gene therapy
> being developed for Parkinson's disease, according to University of Florida
> researchers writing online in advance of September's Molecular Therapy.
>
> The discovery in rats answers an important question — how can new,
> therapeutic genes that have been irrevocably delivered to the human brain to
> treat Parkinson's be controlled if the genes unexpectedly start causing
> problems?
> Meanwhile, in a review of Parkinson treatments, the researchers say that
> prior experimental attempts using growth factors — naturally occurring
> substances that cause cells to grow and divide — to rescue dying brain cells
> may have failed because they occurred too late in the course of the disease.
>
> Together, the findings suggest that gene therapy to enable the brain to
> retain its ability to produce dopamine, a neurotransmitter that falls in
> critically short supply in Parkinson's patients, could be safely attempted
> during earlier stages of the disease with an added likelihood of success.
>
> Parkinson's disease affects more than 1 million Americans, causing patients
> to gradually develop movement problems, including tremors, stiffness and
> slowness. It is caused by degeneration and death of nerve connections that
> produce dopamine, a substance necessary for communication between cells that
> coordinate movement.
> "We have worked every day for 10 years to design a construct to the gene
> delivery vector that enhances the safety profile of gene transfer for
> Parkinson's disease," said Ronald Mandel, a professor of neuroscience at
> UF's McKnight Brain Institute and the Powell Gene Therapy Center. "With that
> added measure of safety, we believe we can intervene with gene transfer in
> patients at earlier stages of the disease. We strongly believe that trials
> to save dopamine-producing connections in patients with Parkinson's disease
> have failed because the therapy went into patients who were in the late
> stages of the disease and who had too few remaining dopamine-producing
> connections."
>
> Often patients are given prescriptions for levodopa, or L-dopa, which is
> converted into dopamine by enzymes in the brain. But the treatment loses its
> effectiveness over time and does nothing to slow the disease's progression.
> Meanwhile, trials in the United States to treat Parkinson's involving
> direct infusion of growth factors or the transplantation of genes that
> produce growth factors have had limited success, with some side effects.
> Mandel's research group has concentrated on using an adeno-associated virus
> to engineer brain cells in animal models with genes that can protect
> dopamine-producing cells, which then do the vital work of producing GDNF,
> short for glial cell line-derived neurotrophic factor. The naturally
> occurring protein is important for the survival of dopamine-producing
> neurons during brain development, and a survival factor when given to
> adults.
> In this case, scientists engineered the virus with two genes that must act
> in concert to produce the protein. But this precise interaction can be
> inhibited with dietary doxycycline, an antibiotic that is often prescribed
> in low doses to treat bacterial growth related to acne.
>
> Depending on the amount of the antibiotic, protein production can be
> reduced or stopped, which would for the first time give medical
> investigators the ability to regulate gene therapy after the treatment was
> delivered.
> "With this technique, you could adjust the therapy in the patient," said
> Fredric P. Manfredsson, a postdoctoral associate in UF's department of
> neuroscience. "That would be extremely helpful because no one is really
> certain yet what dosage is required for a protective effect in humans. The
> process is also much more sensitive than we had imagined it would be. GDNF
> production can be shut down completely with a dose of doxycycline that is
> much smaller than what is commonly prescribed."
> Mandel said that adding the safety construct to the gene vector and proving
> its effectiveness were arduous tasks in which Manfredsson played an
> essential role.
>
> A variety of methods were used to gauge GDNF production, but one was
> uncommon and involved the novel observation of the rats' weight. In prior
> research, the scientists had found delivering the protein to certain regions
> of the brain would hinder weight gain in younger rats and can cause weight
> loss in older rats. In the recent experiments, scientists found they could
> control the rate of weight gain in the rats with dietary doxycycline, which
> essentially verified they were controlling the GDNF therapy.
> "The ability to control gene regulation is important for the future
> development of gene therapy, and optimizing its safe application to humans,"
> said Dr. Mark Tuszynski, a professor of neurosciences and director of the
> Center for Neural Repair at the University of California, San Diego, who did
> not participate in the research. "The work of Dr. Mandel and colleagues
> brings us an important step closer to this goal."
>
> http://www.eurekalert.org/pub_releases/2009-08/uof-usc082809.php
>
>
> __._,_.___
>
>
> __,_._,___
>
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1998, Week 4 August 1998, Week 3 August 1998, Week 2 August 1998, Week 1 July 1998, Week 5 July 1998, Week 4 July 1998, Week 3 July 1998, Week 2 July 1998, Week 1 June 1998, Week 5 June 1998, Week 4 June 1998, Week 3 June 1998, Week 2 June 1998, Week 1 May 1998, Week 5 May 1998, Week 4 May 1998, Week 3 May 1998, Week 2 May 1998, Week 1 April 1998, Week 5 April 1998, Week 4 April 1998, Week 3 April 1998, Week 2 April 1998, Week 1 March 1998, Week 5 March 1998, Week 4 March 1998, Week 3 March 1998, Week 2 March 1998, Week 1 February 1998, Week 5 February 1998, Week 4 February 1998, Week 3 February 1998, Week 2 February 1998, Week 1 January 1998, Week 5 January 1998, Week 4 January 1998, Week 3 January 1998, Week 2 January 1998, Week 1 December 1997, Week 5 December 1997, Week 4 December 1997, Week 3 December 1997, Week 2 December 1997, Week 1 November 1997, Week 5 November 1997, Week 4 November 1997, Week 3 November 1997, Week 2 November 1997, Week 1 October 1997, Week 5 October 1997, Week 4 October 1997, Week 3 October 1997, Week 2 October 1997, Week 1 September 1997, Week 5 September 1997, Week 4 September 1997, Week 3 September 1997, Week 2 September 1997, Week 1 August 1997, Week 5 August 1997, Week 4 August 1997, Week 3 August 1997, Week 2 August 1997, Week 1 July 1997, Week 5 July 1997, Week 4 July 1997, Week 3 July 1997, Week 2 July 1997, Week 1 June 1997, Week 5 June 1997, Week 4 June 1997, Week 3 June 1997, Week 2 June 1997, Week 1 May 1997, Week 5 May 1997, Week 4 May 1997, Week 3 May 1997, Week 2 May 1997, Week 1 April 1997, Week 5 April 1997, Week 4 April 1997, Week 3 April 1997, Week 2 April 1997, Week 1 March 1997, Week 5 March 1997, Week 4 March 1997, Week 3 March 1997, Week 2 March 1997, Week 1 February 1997, Week 5 February 1997, Week 4 February 1997, Week 3 February 1997, Week 2 February 1997, Week 1 January 1997, Week 5 January 1997, Week 4 January 1997, Week 3 January 1997, Week 2 January 1997, Week 1 December 1996, Week 5 December 1996, Week 4 December 1996, Week 3 December 1996, Week 2 December 1996, Week 1 November 1996, Week 5 November 1996, Week 4 November 1996, Week 3 November 1996, Week 2 November 1996, Week 1 October 1996, Week 5 October 1996, Week 4 October 1996, Week 3 October 1996, Week 2 October 1996, Week 1 September 1996, Week 5 September 1996, Week 4 September 1996, Week 3 September 1996, Week 2 September 1996, Week 1 August 1996, Week 5 August 1996, Week 4 August 1996, Week 3 August 1996, Week 2 August 1996, Week 1 July 1996, Week 5 July 1996, Week 4 July 1996, Week 3 July 1996, Week 2 July 1996, Week 1 June 1996, Week 5 June 1996, Week 4 June 1996, Week 3 June 1996, Week 2 June 1996, Week 1 May 1996, Week 5 May 1996, Week 4 May 1996, Week 3 May 1996, Week 2 May 1996, Week 1 April 1996, Week 5 April 1996, Week 4 April 1996, Week 3 April 1996, Week 2 April 1996, Week 1 March 1996, Week 5 March 1996, Week 4 March 1996, Week 3 March 1996, Week 2 March 1996, Week 1 February 1996, Week 5 February 1996, Week 4 February 1996, Week 3 February 1996, Week 2 February 1996, Week 1 January 1996, Week 5 January 1996, Week 4 January 1996, Week 3 January 1996, Week 2 January 1996, Week 1 December 1995, Week 5 December 1995, Week 4 December 1995, Week 3 December 1995, Week 2 December 1995, Week 1 November 1995, Week 5 November 1995, Week 4 November 1995, Week 3 November 1995, Week 2 November 1995, Week 1 October 1995, Week 5 October 1995, Week 4 October 1995, Week 3 October 1995, Week 2 October 1995, Week 1 September 1995, Week 5 September 1995, Week 4 September 1995, Week 3 September 1995, Week 2 September 1995, Week 1 August 1995, Week 5 August 1995, Week 4 August 1995, Week 3 August 1995, Week 2 August 1995, Week 1 July 1995, Week 5 July 1995, Week 4 July 1995, Week 3 July 1995, Week 2 July 1995, Week 1 June 1995, Week 5 June 1995, Week 4 June 1995, Week 3 June 1995, Week 2 June 1995, Week 1 May 1995, Week 5 May 1995, Week 4 May 1995, Week 3 May 1995, Week 2 May 1995, Week 1 April 1995, Week 5 April 1995, Week 4 April 1995, Week 3 April 1995, Week 2 April 1995, Week 1 March 1995, Week 5 March 1995, Week 4 March 1995, Week 3 March 1995, Week 2 March 1995, Week 1 February 1995, Week 4 February 1995, Week 3 February 1995, Week 2 February 1995, Week 1 January 1995, Week 5 January 1995, Week 4 January 1995, Week 3 January 1995, Week 2 January 1995, Week 1 December 1994, Week 5 December 1994, Week 4 December 1994, Week 3 December 1994, Week 2 December 1994, Week 1 November 1994, Week 5 November 1994, Week 4 November 1994, Week 3 November 1994, Week 2 November 1994, Week 1 October 1994, Week 5 October 1994, Week 4 October 1994, Week 3 October 1994, Week 2 October 1994, Week 1 September 1994, Week 5 September 1994, Week 4 September 1994, Week 3 September 1994, Week 2 September 1994, Week 1 August 1994, Week 5 August 1994, Week 4 August 1994, Week 3 August 1994, Week 2 August 1994, Week 1 July 1994, Week 5 July 1994, Week 4 July 1994, Week 3 July 1994, Week 2 July 1994, Week 1 June 1994, Week 5 June 1994, Week 4 June 1994, Week 3 June 1994, Week 2 June 1994, Week 1 May 1994, Week 5 May 1994, Week 4 May 1994, Week 3 May 1994, Week 2 May 1994, Week 1 April 1994, Week 5 April 1994, Week 4 April 1994, Week 3 April 1994, Week 2 April 1994, Week 1 March 1994, Week 5 March 1994, Week 4 March 1994, Week 3 March 1994, Week 2 March 1994, Week 1 February 1994, Week 4 February 1994, Week 3 February 1994, Week 2 February 1994, Week 1 February 1994 January 1994 December 1993 November 1993
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