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.

SAEN: Animal Research? Must Be The Money!

Stop Animal Exploitation Now’s Leana Stormont held a press conference at the University of Iowa in February to denounce animal research outside Spence Laboratories.

Spence Laboratories was the site of a much-publicized Animal Liberation Front attack last year, in which animals were stolen and machinery was smashed by extremists.

Stormont held a press conference outside Spence saying that the only reason researchers at the University of Iowa were continuing to conduct animal research was to enrich themselves.

Stormont said,

Barbaric experiments are under way at the University of Iowa. This is not about science. This is about money — attracing hundreds of thousands of dollars to UI’s coffers.

But Stormont seems to have limited knowledge about the research going on at the University of Iowa. The Iowa City Press-Citizen noted that Stormant denounced University of Iowa researcher Gary Van Hoesen research on macaques.

Just one problem, according to the Press-Citizen,

However, Van Hoesen said he has not used monkeys since 1982. He now conducts research on the human brain related to Alzheimer’s disease

Animal rights activists’ compassion is matched only by their accuracy.

Update/Correction: Thanks to Rick Bogle for pointing out that there are serious problems with the Press-Citizen’s reporting above that Van Hoesen has not done any research on monkeys since 1982. Van Hoesen is, in fact, listed as the last author on a number of studies that involve research on monkeys in recent years. Van Hoesen is probably correct that he hasn’t personally done any research on monkeys, and his name is probably being add as the last author due to convention of adding senior researchers and program heads on research that comes out of their department (Van Hoesen is the director of the Alzheimer’s disease program at the University of Iowa). But Stormont was being completely reasonable, in my opinion, in assuming that Van Hoesen was conducting research on monkeys since his name was attached to a number of such studies, and the Press-Citizen and/or Van Hoesen was being grossly unfair and deceptive in depicting Stormont as being ignorant or relying on outdated information. AnimalRights.Net regrets reproducing the Press-Citizen’s deceptive characterization of Stormont.

Sources:

UI target of animal rights group. Kristen Schorsch, Iowa City Press-Citizen, February 11, 2005.

Group pressures University of Iowa to halt animal research. Associated Press, February 11, 2005.

Jeremy Beckham Leads Protest Against University of Utah Researcher

The Salt Lake Tribune reported in January on a protest involving about 25 animal rights activists against University of Utah researcher Allesandra Angelucci.

The protest was organized by University of Utah student and Utah Primate Freedom Project’s Jeremy Beckham, who has crossed path with the University on a number of occasions.

The protesters used typical animal rights distortions. According to the Salt Lake Tribune (emphasis added),

On the street below [Angelucci’s residence], about 25 protesters held candles and signs proclaiming the immorality of primate research. Flashing images of caged monkeys lit the street from the four 100-inch screens of the “Tiger Truck” — essentially a moving van mounted with giant TVs. The truck was on loan to Beckham from the Showing Animals Respect and Kindness organization. The images displayed on its screens were captioned with brief insults like: “Angelucci gets rich abusing animals” and “Be advised: Ms. Angelucci has a violent nature. Keep pets away from her.” None of the images, however, were from the University of Utah, Beckham said.

According to the Salt Lake Tribune, Angelucci received a $400,000 primate research grant in August 2004 and this was the second protest against her home.

University of Utah spokeswoman Coralie Alder told the Salt Lake Tribune that Beckham has a First Amendment right to protest, but that, “We support the right of our faculty members to pursue their work from intimidation.”

Source:

Protesters gather outside researcher’s home. Michael Westley, The Salt Lake Tribune, January 31, 2005.

Small Study of Macaques and BSE Suggests Low Transmission Risk

British medical journal, The Lancet, published the results of a small-scale French study into the transmissibility of bovine spongiform encephalopathy (BSE). The results confirm what the evidence and computer models have already implied — that the risk of transmission of BSE from animals to humans in the form of vCJD is very low. The small size of the study, however, do limit the ability to extrapolate from the study.

Researchers took two adult macaque monkeys and exposed them to five grams of brain tissue from a BSE-infected cow. After five years, one of the macaques developed symptoms of a vCJD-like disease while the other macaque remains health and symptom-free.

The French researchers suggest that in order to have a sizable risk of infection, and individual would have to eat about 3.3 pounds of meat from an infected cow. Since current slaughterhouse regulations in the UK and elsewhere are able to detect BSE-infected meat when it hits a threshhold slight less than that from an infected cow, the French research suggests that such existing regulations are well tuned to prevent further such infections.

The researchers also suggest that the incubation period for BSE in humans could be, on average, greater than 50 years, which would explain why so few people have died from vCJD despite presumably widespread exposure to BSE-infected beef in the UK. Other studies have suggested that the vCJD incubation period may, on average, be significantly longer than current human lifespans.

The vCJD epidemic appears to have peaked in Great Britain. Where 18 people died from vCJD in 2003, only 9 people succumbed to the disease in 2004 and there are only five additional suspected cases of the disease in Great Britain.

Sources:

Study optimism on mad-cow disease. News.Com.Au, January 27, 2005.

Risk of oral infection with bovine spongiform encephalopathy agent in primates. Corinne Ida Lasmézas, et al., The Lancet, January 27, 2005.

Activists Protest at UCLA Neuropsychology Building

As part of National Primate LiberatioN Week, the Daily Bruin reported that animal rights activists marched from the Federal Building in Los Angeles to the University of California – Los Angeles Neuropsychology building to protest primate research that UCLA carries out.

According to the Daily Bruin, the protest was put together in response to a report released by Michael Budkie of Stop Animal Exploitation Now! that primate research in the United States is expanding overall. Budkie told the Daily Bruin that his group hoped to appeal to faculty and students to change minds about primate research,

Whlie some people at universities get paid to perform experiments, I know that other scientists have higher ethical standards.

The Daily Bruin quoted protester Dena Snedden repeating the animal rights line that animal research is driven largely by greedy animal researchers,

It’s time that they explore and implement humane medical research. The technology is there. The reason this [animal research] is happening is to line certain individuals’ pockets at the animals’ expense and the public’s expense.

Lets take a look at one of these greedy bastard researchers, Lynne Fairbanks, whom the protesters named as one of UCLA’s primate researchers.

Fairbanks’ recent research has centered centers on understanding the neurobiology of human interactions — i.e. the role that brain and body chemistry plays in alcoholism, drug addiction, depression, ADHD and a variety of other common psychological ailments. In 2001, for example, Fairbanks was the lead author of a research paper published in Neuropsychopharmacology. That research, involving vervet monkeys, linked abnormal serotonin activity to poor impulse control and aggression in the monkeys.

What sort of sick, greedy person would want to better understand the role that brain chemistry plays in human behavior, especially abnormal or harmful human behavior?

Sources:

Protest held for primate liberation. Lee Bialik, Daily Bruin, October 5, 2004.

Monkeys, rats shed light on roots of impulsivity. Crime Times, V.7, No.3, 2001.

Taking a Different Approach in HIV Research — Blocking Transmission in Animal Models

A lot of the high profile HIV animal research has been directed at finding vaccines for the virus which have, so far, all failed to perform in clinical testing. But there are a number of other avenues of research including research focused better understanding how the disease is transmitted and looking for ways to stop that transmission.

In October, Science published the results of research conducted in the United States and Switzerland that managed to block transmission of the simian HIV in macaque monkeys.

In both human beings and macaques, the HIV virus can be transmitted across mucous membranes in the vagina and cervix. The virus uses a number of molecules to accomplish this task, including one called CCR5. CCR5 is so important to HIV transmission, that human beings who lack CCR5 due to genetic variations are all but immune from HIV infection.

Researchers at the University Hospitals of Cleveland Center for AIDS Research and University of Geneva in Switzerland created a compound that binds with CCR5. They then applied the compound to the vaginal surfaces of macaque monkeys, waited 15 minutes, and then exposed the macaques to SHIV.

The result? Of the macaques who received the highest dosage level of the CCR5-inhibiting compound, 12 of 15 animals did not become infected.

This research is a long way from any clinical trials, but if it is possible to cheaply manufacture a microbicide that would block CCR5 in human beings, it would be an extremely important advance.

As AIDS researcher Donald Mosier told Bio.Com,

Virtually all HIV [strains] use the CCR5 receptor. [So, completely] blocking CCR5 would block 99 percent of HIV transmission worldwide.

Sources:

HIV in monkeys ‘blocked by drug’. The BBC, October 14, 2004.

A Simple Strategy for Blocking HIV Transmission Proves Effective in Pre-Clinical Trials. Jason Socrates Bardi, Bio.Com, October 18, 2004.

Microbicide Shuts the Door on HIV. Jon Cohen, Science, October 15, 2004.