Tag: Parkinson’s Disease

Gene Therapy Used to Prevent Parkinson’s Disease in Primates

In February, the The Journal of Neuroscience published the results of efforts to use gene therapy to boost levels of a protein that is believed to preserve brain cells and may someday form the basis of a treatment for Parkinson’s Disease.

The protein is glial cell line-derived neurotrophic factor (GDNF). It has been tested in human beings but so far with mixed results. A trial of GDNF therapy in human beings had to be stopped in October 2004 due to safety concerns. In that trial, GDNF was introduced directly into the brain of 34 patients. Four of the patients developed antibodies against GDNF within six months of the trial. In conjunction with research on primates that found the brain cells of the animals began to break down after the GDNF treatment, the human trial was stopped.

An earlier smaller-scale trial of GDNF in the UK showed improvement in Parkinson’s patients given GDNF, and there’s debate over whether the difference in the two studies is related to the effect of GDNF or possible differences in the protocols of the two studies.

A couple teams of international researchers, however, recently published their results of another method of delivering GDNF — using gene therapy to force the bodies of affected animals to produce GDNF. There are likely to be a number of advantages to this over the current practice of simply introducing it directly into the brain, including producing GDNF at levels that are likely to be safer for the patient.

In research sponsored by Lund University in Lund, Sweden; the University of Cambridge; and the McKnight Brain Institute and the Genetics Institute of the University of Florida, researchers used gene therapy to insert copies of a gene responsible for creating GDNF in the front part of the brain into monkeys. Researchers then induced an animal model of Parkinson’s in the monkeys by exposing them to a drug that destroys dopamine producing cells.

After 17 weeks, monkeys that had received the gene therapy not only had a significantly higher ability to perform tasks than a control group that did not receive the gene therapy, but analysis of brain tissue showed the GDNF had a protective affect on the dopamine producing cells in the experimental group of monkeys.

Dr. Nicholas Mzyczka, of the University of Florida’s College of Medicine, said in a press release announcing the results,

The simplest question we’re asking is, “Does any particular combination of proteins prevent or accelerate degeneration of the neurons?” For some time Dr. [Ron] Mandel has been working on the idea of introducing a vector into the brain that would express GDNF. What they’ve found is that if you get low-level expression, you can prevent cell death in a part of the brain called the substantial nigra. That’s been shown before in rodent models, but it’s encouraging to see data that it works in higher animals like monkeys.

In the same press release, Mandel said of the current status of GDNF as a possible treatment for Parkinson’s,

Our strategy is a neuroprotective concept and would only be amenable for early stage patients to keep a good quality of life. It would be a huge change in the way treatment is done. We know the GDNF protects the neurons in primates from the model that we use, so that’s good. We know we can use very low doses that are still effective, so that’s good. But we need a safety net. Once we turn it on, it’s on for life. So we have to control it, and we’re working on this as we speak. But it’s not ready for clinical trials.

Source:

Gene therapy for Parkinson’s Disease moves forward in animals. Press Release, University of Florida Health Science Center, February 10, 2005.

Parkinson’s trial halted. Helen Pearson, Nature, October 5, 2004.

Embryonic Stem Cells Cure Parkinson's-Like Disease in Mice

In September, U.S. researchers reported in Nature Biotechnology that they had used stem cells to cure mice who were bred to suffer from a Parkinson’s-like condition.

Researchers at the Stem Cell and Tumor Biology Laboratory took cells from the tails of the mice and used that to clone embryos. Stem cells from the embryos were then taken and altered to grow into a type of brain cell that the mice were missing. That tissue was then implanted into the brains of the mice.

The researchers reported that the Parkinson’s-like conditions in the mice disappeared after the tissue implant.

Dr. Lorzen Studer, lead research on the study, told the BBC that this research provided a proof of concept that embryonic stem cells could be used in this way, but that there are still many hurdles to overcome before this could be tested on human beings (not the least of which, in this case, would be the creation and use of embryonic stem cells which is still the subject of much ethical hand wringing).

Studer added that,

We don’t know if we would be able to do the same thing in humans — there is some research, which is controversial — that suggests that it might actually be impossible.

A similar study in 2002 also produced positive results when stem cells from mouse embryos were altered to produce brain tissue and then implanted into rats. That study, conducted at the University of Minnesota, showed that the transplanted stem cells grew into neurons in the brains of the rat and improved — though didn’t completely erase — the Parkinson’s-like symptoms suffered by the rats.

Source:

Mouse cloned to cure Parkinson’s. The BBC, September 21, 2003.

Embryonic Mouse Stem Cells Reduce Symptoms in Model for Parkinson’s Disease. National Institute of Neurological Disorders and Stroke, June 25, 2003.

Home Office Investigation Clears Cambridge University Laboratory of Wrongdoing

Last May, the British Union for the Abolition of Vivisection released video footage that it claimed showed monkeys at a Cambridge University laboratory being abused by their caretakers who were not reporting the level of suffering actually experienced by the animals (see this story for background).

In February the UK Home Office released the results of its investigation which concluded that the primate laboratory was well managed and that there was no evidence of abuse nor any evidence that there was any sort of withholding of information by animal researchers or caretakers at Cambridge University.

According to the Home Office report (full report – PDF), the Cambridge University researchers did not cause any more suffering than was necessary to carry out their research on brain disorders such as amnesia, dementia, and Parkinson’s disease and that, moreover, the primate facility,

. . . meets, and in some respects exceeds the standards of housing and care set out in the relevant Home Office Codes of Practice, and that some examples of best practice are to be found there.

BUAV, meanwhile, condemned the report saying it was,

. . . utterly appalled and deeply angered by the complete dismissal of overwhelming evidence of animal suffering.

But the report noted numerous problems with BUAV’s videotapes,

The campaign videotape includes covert recordings of animals in the immediate and early-postoperative periods. The condition of the animals shown reflects a combination of the early effects of the surgery and anaesthesia, and the post-operative medication given. The surgical incisions shown reflect the extent of the surgical exposure required rather than the magnitude of the surgical procedure performed.

In some cases, BUAV outright distorted issues that laboratory personnel themselves had raised. Again, from the Home Office report on BUAV’s claim about overcrowding at the primate facility,

The BUAV report makes mention of stocking levels reaching “critical points” during 1999/2000 and needing to be resolved with “with [sic] some urgency.” Contemporary records confirm that the issue under consideration was how to manage breeding performance and available animal accommodation in order to remain in compliance rather than to deal with stocking levels that had resulted in non-compliance [as the BUAV report clearly implied].

Similarly, BUAV’s claims about other aspects of animal welfare don’t hold up under scrutiny. In its report, for example, BUAV claimed that “Common problems with primate groups include fighting injuries and bacterial and viral infections . . .” But according to the Home Office report,

The BUAV report suggests that animal health and welfare problems are commonplace in the animals bred, kept and used in the Cambridge facility. The specifics discussed include fight-related injuries, diarrhea, respiratory tract infections and dental abscesses.

. . . bearing in mind that the unit houses over 400 animals at anyone time, recorded injuries from fighting are uncommon. In 1999 there were two unequivocal confirmed cases of fight-related injuries, and a further five minor injuries where fighting may have played a part. In 2000 there were no confirmed cases, and only four minor other injuries where fighting may have played a part. In 2001 there were two confirmed fight-related injuries, and three other minor injuries where fighting may have played a part.

Diarrhea occurs occasionally. It is generally mild and sporadic, and seldom lasts for more than one day. Cultures are taken from all animals believed to have an infective disorder. Only one Salmonella infection has been recorded since May 1999.

Infective respiratory problems, that is significant upper respiratory tract infections and/or pneumonia, are uncommon and sporadic. Transmission is generally restricted to cage mates. These conditions are not endemic within the colony. Contemporary documents record five cases in 2000, and nine cases in 2001, again at times when the facility housed over 400 animals. The BUAV report describes an outbreak of pneumonia caused by Bordtella bronchispetica affecting five members of one family group in 2001. Rather than illustrating a chronic, widespread or endemic problem, the outbreak discussed in the BUAV report accounted for more than half of the respiratory tract infections recorded in 2001.

More proof that you simply can’t take animal rights-produced videos and still photos at face value. BUAV, for its part, seemed more interested in creating video footage for its own purposes than actually helping to stop alleged animal abuse at the Cambridge University laboratory. For example, consider this odd statement from the Home Office report,

Cambridge University co-operated fully with this review.

The Home Office invite BUAV to provide the evidence on which their concerns are based, and to allow their investigator to be interviewed for the purposes of this review. BUAV declined.

How predictable.

Sources:

A Review By The Chief Inspector Of The Animals (Scientific Procedures) Inspectorate Of Aspects Of Non-Human Primate Research At Cambridge University.

Monkey research cleared by report. Roger Highfield, The Daily Telegraph, February 12, 2003.

Aspects of Non-human Primate Research at Cambridge University: A Review by the Chief Inspector. UK Home Office, October 2002.

Dolly Researchers Turn Skin Cells into Stem Cells

Researchers who helped clone Dolly the Sheep have turned what they learned there into an incredible breakthrough. Researchers at the U.S. subsidiary of PPL Therapeutics last week announced they had managed to turn cells from the skin of cows into stem cells. They were then able to turn the stem cells into functioning heart cells.

This has a number of important implications for human research. Stem cells of the sort announced by the researchers are typically found only in fetuses. Those stem cells can become literally any other type of cell if given the correct signals.

As organisms grow and age, however, the stem cells become differentiated and able to transform into fewer and fewer different types of tissue. This is necessary to control development of the organism.

For this reason, research involving stem cells in human beings has to date required the controversial use of fetal tissue. Experimental treatment for |Parkinson|’s disease, for example, uses fetal tissue in an attempt to spur growth of neurons in the brain.

Because of the ongoing controversy over abortion, use of fetal tissue has proven to be a political minefield (Great Britain is the only government in the world that currently allows government funding for such projects), and there are other limitations. Taking adult cells, such as from the skin, and turning back the clock, so to speak, to transform them into undifferentiated stem cells has been one of the ultimate goals of genetic research.

Dr. Ron James, managing director of PPL Therapeutics, told the BBC, “The results of this experiment give us confidence that the method we are developing as a source of stem cells is working and I believe it will be equally applicable to humans.”

If that proves to be true, which is an enormous if, it could revolutionize medical treatments leading to such science fiction-like scenarios as growing replacement for defective hearts and other organs.

Source:

Tissue transplant advance. The BBC, February 23, 2001.

Parkinson's Breakthrough in Monkey Research

Researchers experimenting with monkeys successfully tested a gene therapy technique that reversed the brain damage associated with Parkinson’s disease.

For reasons that are still not understood, people suffering from Parkinson’s disease do not produce enough of the brain chemical dopamine which is necessary for signals in the brain to be transmitted. As a result Parkinson’s sufferers experience a degenerative loss of motor control including difficulty walking, talking, smiling and swallowing. Secondary effects such as pneumonia and stroke end up killing many with Parkinson’s diseases.

In a study published in Science, scientists used a group of eight monkeys with a Parkinson’s-like disease and another group of eight monkeys without the disease. The monkeys suffering from the brain disease were injected with a genetically altered virus that was designed to boost dopamine production within the brain.

In both cases the virus dramatically boosted brain dopamine levels over the eight months of the of the study and ameliorated the Parkinson’s-like symptoms that the monkey’s experienced. Three of the monkeys in the first group who had severe Parkinson’s symptoms were restored to almost normal motor functions according to study author Jeffrey Kordower.

In the second group, five of the monkeys who developed Parkinson’s were given the virus while five were not. One monkey in each group died for unknown reasons. Of the four in each group left, three with the Parkinson’s symptoms were completely free of the disease after receiving the virus injection, while all four monkeys in the control group became severely impaired.

The researchers will soon be present the FDA with a proposal to test the gene therapy in humans and such trials could begin in 3 to 5 years. One possible obstacle is that the researchers are not sure if the brain cells that are responsible for dopamine production in human beings will respond in the same way that their counterparts in the monkeys did. Even if they don’t, however, this is important evidence that gene therapy designed to modify brain cells of Parkinson’s suffers to boost dopamine levels is likely to be a very viable avenue of research, even if the methods used to get there might be different in human beings than in monkeys.

Source:

Hope of Parkinson’s ‘cure’. The BBC, October 27, 2000.

Gene therapy may relieve Parkinson’s disease. Paul Recer, The Associated Press, October 26, 2000.

Attack on University of Minnesota Worst Lab Attack in Recent Years

On April 5, the Animal Liberation Front claimed responsibility for a raid on a University of Minnesota lab
that released over 100 animals and vandalized the lab doing more than
$2 million in damage.

The lab was conducting experiments
with rats, pigeons, salamanders and mice on a variety of research projects
including efforts to better understand cancer and Parkinson’s disease.
Dr. Walter Low, a researcher at the University of Minnesota, said the
raid set back studies being conducted on Alzheimer’s by at least two years
(the University of Minnesota is well known for developing a strain of
mice that mimic the traits often found in Alzheimer’s patients.)

Along with freeing the lab
animals, the ALF operatives smashed computers, wrecked microscopes and
photocopiers and even destroyed human tissue that were part of a research
program to find a vaccine to attack brain tumors. As Low pointed out,
this is rather ironic since the animal rights activists insist tissue
cultures should be used to replace animals in medical research.

Several people in the Minnesota
area, including a cancer patient, are offering a reward of $10,000 for
information leading to the capture and conviction of the perpetrators.

The reaction from animal rights
groups was predictable. Lisa Lange of People for the Ethical Treatment of Animals
was quoted in New Scientist as saying, “We do things in a very different
way, but I understand their frustration. The real crime is that millions
of animals are being tortured and killed.”

On the other hand Freeman Wicklund, executive director of the nonprofit Animal Liberation League,
told the Minneapolis Star Tribune that such actions hurt the animal rights
cause. “We hope everybody realizes that the visible minority within
the animal-rights community doesn’t represent the broader movement,” Wicklund said. “A
lot of people who care about animals are upset about the actions.”

Although it is nice to see
Wicklund oppose such raids, he is ignoring reality when he implies
his view is in the majority. In fact he has been widely denounced by animal
rights activists for his stance against terrorist activities.

Sources:

Animal activists suspected in lab damage. Jim Adams, Minnesota Star Tribune, April 6, 1999.

Activists up the ante. Kurt Kleiner, New Scientist, April 17, 1999.

Research labs vandalized, 75 animals taken. Associated Press, April 6, 1999.

NC A.L.F. Liberates 116 from Vivisection Lab. No Compromise, Press Release, Arpil 9, 1999.

Doctor refutes claim animal experiments have brought us closer to cure for Alzheimer’s disease, call such claims “exploitative” of stricken families. New England Anti-Vivisection Society, Press Release, April 9, 1999.

Veternarian charges U of M experimenters exaggerated claims of research progress. In Defense of Animals, Press Release, April 9, 1999.

ALF tactics condemned. Letter to the editor, Minnesota Daily, April 9, 1999.

More lost U lab animals found in Woodbury field. Jim Adams, Minnesota Star Tribune, April 9, 1999.

Minn. research labs vandalized. Associated Press, April 6, 1999.

Animal Liberation Front claims responsibility for liberation of 116 animals from University of Minnesota, while destroying violent research. North American Animal Liberation Front Press Office, Press Release, April 5, 1999.

A.L.F. Raids University of Minnesota Animal Lab. North American Animal Liberation Front Press Office, Press Release, April 5, 1999.

Vigil for lab animals. Animal Liberation Front, Press Release, April 7, 1999.