A decades-old drug made from human plasma appears to slow the decline of mental skills in people with Alzheimer's disease, suggest results from a small preliminary study.
The drug is called Gammagard. It's a form of intravenous immunoglobulin, or IVIG, drugs that are usually used to treat immune system disorders.
Researchers believe the drug can replenish a depleted pool of natural antibodies against beta-amyloid protein, which forms the sticky plaques that riddle Alzheimer's patients' brains.
In the new study of 24 patients, scores on a standard test measuring the disturbances of memory, language, attention, and other cognitive skills that are hallmark symptoms of Alzheimer's disease dropped an average of slightly more than five points in those treated with IVIG. That compares with a 15-point decline in patients who initially received placebo and switched to IVIG, says Norman Relkin, MD, of Cornell Weill College of Medicine in New York City. The IVIG treatment also appeared to slow the rate of brain shrinkage by about 45%.
General Research Outcomes
Alzheimer's disease patients treated with Baxter International's Gammagard for 18 months:
- Showed better cognitive function and less brain enlargement than those given a placebo.
- Patients with mild to moderate Alzheimer's disease who received the intravenous medication in a Phase II study averaged about 1.36 points higher than patients who initially received a placebo on a test of mental abilities.
- On a second cognitive performance test, patients who received Gammagard declined by about 9.15 fewer points than placebo patients.
- MRI analyses also showed patients treated with Gammagard saw a 6.7 percent decrease in annual ventricular enlargement in their brains, compared to a 12.3 percent rate in patients on a placebo.
Relkin says Gammagard produced "benefits like I've never seen before." He says he had one patient, a former piano player, who played the same four compositions over and over. "Four to six months into the study, he sight-read a new piece for the first time in years. Over the next few months, the patient continued to improve his repertoire," Relkin says.
Since IVIG has been around for years, its side effects in the general population are well known: headaches, rashes, and blood pressure elevation.
"By and by, it's well tolerated," Relkin says. "But we don't yet know the side effect profile in an elderly, Alzheimer's disease population."
One thing that is known: The treatment is expensive -- about $2,000 to $3,000 per treatment. And patients in the study received infusions up to twice a month, depending on the dose, for 18 months.
In the study, eight patients received a placebo and 16 got one of four doses of Gammagard every two to four weeks. After 12 weeks, patients in the placebo group switched over to Gammagard at the same range of doses.
Patients were evaluated every three months using standardized Alzheimer's tests and MRI scans.
Dr. Lisa Mosconi, assistant professor of psychiatry at New York University Medical Center, worked with the New York-Presbyterian/Weill Cornell group on the analysis of brain imaging data from the study. She reported that Gammagard -treated participants had observable changes in brain metabolism. While energy metabolism in the brain was an exploratory endpoint in the study it was preserved or improved in 10 out of 13 patients after six months of Gammagard-S/D and Gammagard-Liquid treatment.
“Brain metabolism usually decreases progressively in patients with Alzheimer’s disease,” said Dr. Mosconi. “The changes on PET scans of these Alzheimer’s patients after six months of Gammagard-S/D and Gammagard-Liquid are encouraging.”
On top on the generally positive research outcomes, there was few really outstanding personal conditions improvement in some participants. There were even some patients that showed noticeable reversal in Alzheimer’s symptoms. One patient, a pianist, was formerly only able to remember and play about four songs. After the 18 month trials, family members reported that the patient had started to learn new songs.
The results are "very encouraging," says Stephen Salloway, MD, a professor of neurology at Brown University who was not involved with the research.
"To see any signal [that the drug is working] in a study this small is unexpected," he tells WebMD. "This is the type of response we are hoping for."
But another researcher urged caution.
"This is a very small phase II study whose purpose is really just to establish the correct dose," Ron Peterson, MD, director of the Mayo Alzheimer's Disease Research Center in Rochester, Minn., tells WebMD. "In the past few years alone, several Alzheimer's drugs that made it to this stage failed to pan out in further testing."
A larger phase III trial of 360 patients pitting the drug against placebo is under way, according to Relkin.
The study was funded by Baxter, which makes Gammagard.
Gammagard is contraindicated in patients with known anaphylactic or severe hypersensitivity responses to Immune Globulin (Human). Patients with severe selective IgA deficiency (IgA < 0.05 g/L) may develop anti-IgA antibodies that can result in a severe anaphylactic reaction. Immune Globulin Intravenous (Human) products have been reported to be associated with renal dysfunction, acute renal failure, osmotic nephrosis, and death. Patients predisposed to acute renal failure include patients with any degree of pre-existing renal insufficiency, diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs. Especially in such patients, IGIV products should be administered at the minimum concentration available and the minimum rate of infusion practicable. While these reports of renal dysfunction and acute renal failure have been associated with the use of many of the licensed IGIV products, those containing sucrose as a stabilizer accounted for a disproportionate share of the total number. Glycine, an amino acid, is used as a stabilizer. Gammagard does not contain sucrose. Gammagard is made from human plasma. It may carry a risk of transmitting infectious agents, viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent.
Sources and Additional Information:
For the first time in history, a clinical trial drug stabilized Alzheimer's for 3 straight years. The long-term stabilization of Alzheimer's symptoms was achieved in people with Alzheimer's receiving Gammagard infusions every two weeks.
Gammagard succeeded to stop Alzheimer's in a number of categories, including no decline in:
- Daily functioning.
The study demonstrated that:
- Participants receiving treatment every two weeks for the full 36 months had the best outcome. They showed no decline whatsoever on their average scores in cognition, memory, daily functioning and mood.
- The 11 participants who received Gammagard treatments for the full 36 months had favorable outcomes in terms of their thinking abilities, behavior and daily function.
- The five participants who were initially treated with a placebo and then switched to Gammagard declined while on placebo. However, when they were switched to steady Gammagrd treatments, they experienced less rapid decline.
Early next year, the results of a much larger Phase-3 clinical trial will be released. That should offer the real proof of Gammagard's effectiveness.