World Bulletin / News Desk
In a new lead on Alzheimer's research, Johnson & Johnson is bankrolling a three-year pilot study of people with Down syndrome to identify the early changes that herald dementia, which afflicts up to 75 percent of adults with the condition.
The aim is to generate support for a much bigger, public-private partnership funded by drugmakers, advocates and government agencies that will study at least 1,000 people with Down syndrome, tracking them from an early age and eventually testing treatments to keep dementia from developing.
"The study we're proposing would provide insight into treating Alzheimer's, but it might help individuals with Down syndrome as well," said Dr. Husseini Manji, J&J's global head of neuroscience drug development.
Experts in Down syndrome and Alzheimer's who gathered in Chicago for a workshop on the idea at the Alzheimer's Association offices this month say it may offer the best scientific model yet for testing drugs to prevent the degenerative brain disease.
Alzheimer's is the most common form of dementia, affecting some 36 million people worldwide. Current drugs only treat symptoms, and none have yet been able to keep the fatal disease from progressing. It has proven a tantalizing prospect for drugmakers, as a success would be worth billions of dollars.
But companies have been repeatedly stung by costly failures, including recent trials of the J&J and Pfizer Inc Alzheimer's treatment bapineuzumab. As a result, companies and researchers are looking for ways to test Alzheimer's drugs earlier, before people's brains become too damaged to benefit.
Studies are already planned to enroll people who carry genetic mutations that ensure they will develop Alzheimer's at an early age. One trial backed by the U.S. Department of Health & Human Services will test a drug from Roche Holding AG's Genentech unit called crenezumab in an extended family from Colombia who carry a mutation that causes them to develop Alzheimer's in their 30s.
Only a few hundred families in the world carry these genes, and there is some worry that drugs tested in people with genetic mutations that cause early-onset Alzheimer's may work differently in people who develop the more common late-onset Alzheimer's, which develops after age 65.
AN IMPORTANT DIFFERENCE
The dementia that develops in people with Down syndrome may bear a stronger resemblance to the disease in the broader population because it differs from other forms of early-onset Alzheimer's, researchers say.
People with Down syndrome inherit a third copy of chromosome 21, giving them an extra helping of a gene that makes amyloid precursor protein, or APP, which is linked with the development of plaques in the brains of Alzheimer's patients.
Most early-onset Alzheimer's is caused by mutations in the APP gene or in one of two genes known as presenilin 1 or presenilin 2. People with Down syndrome appear to develop dementia because of their extra copy of an otherwise normal APP gene.
"There is a possibility that the Down syndrome population mimics (late-onset) Alzheimer's disease a little more closely," said Manji, co-author of a commentary this month in Nature Reviews Drug Discovery that laid out plans for the study.
Dementia starts much earlier in people with Down syndrome, who develop brain plaques and tangles by age 30 and signs of dementia by age 40.
The number of potential Down syndrome patients exceeds those with the genetic mutation. There are some 400,000 people in the United States and 6 million people worldwide with Down syndrome.
"These diseases almost certainly have common features," said Dr. William Mobley of the Down Syndrome Center for Research and Treatment at the University of California, San Diego.
While all of the similarities are not yet clear, studies in mice with Down syndrome show that just eliminating just the extra copy of the gene for APP can keep brain cells from dying, he said.
Mobley's center will run the 12-patient pilot study, which aims to lay the foundation for the larger project, dubbed the Down Syndrome Biomarker Initiative.
The larger trial would be patterned after two successful studies: the Alzheimer's Disease Neuroimaging Initiative, a public-private partnership that helped identify biomarkers linked with Alzheimer's, and a breast cancer trial known as I-SPY that pioneered adaptive trial design, in which researchers use biomarkers to match the right drug to the right patient.
What is not yet known is how many parents of people with Down syndrome would be willing to sign up their adult children for such trials. Michelle Whitten of the Global Down Syndrome Foundation thinks many will be.
Whitten, the mother of a 9-year-old with Down syndrome, says the lifespan of people with the condition has increased from 28 years in the 1980s to 60 years today because of better treatment. That means many parents who fought to give their children a good education and a worthwhile job now frequently face their decline into dementia.
"We just want it solved," Whitten said.
Dr. Michael Krams, who heads the neurology franchise at J&J, said the challenge is to develop drugs that offer lots of potential benefit with little risk to patients.
That may rule out the company's drug bapineuzumab, which was shown to cause brain-swelling known as vasogenic edema in several patients.
Krams said one promising approach would be a beta-secretase, or BACE, inhibitor, a drug designed to keep the enzyme beta-secretase from chopping up APP into bits that produce beta amyloid, which forms brain plaques in Alzheimer's patients.
A recent study in the journal Nature hinted that inhibiting beta-secretase might work. A team at deCODE Genetics in Reykjavik discovered a rare mutation in the APP gene that protects against Alzheimer's, and it works by interfering with beta-secretase. Drugmakers who are already developing BACE inhibitors include Eli Lilly and Co, Roche, and Merck & Co.
Krams declined to say if J&J also has a BACE drug, but he said testing such drugs in patients with late-onset Alzheimer's would require very large trials.
"At least conceptually, doing this in a Down's population might be much more efficient."
Around 6.5 million deaths globally are attributed each year to poor air quality inside and outside, making it the world's fourth-largest threat to human health, behind high blood pressure, dietary risks and smoking
New World Drug Report research identifies heroin as deadliest drug
Zika has caused alarm throughout the Americas since cases of the birth defect microcephaly were reported in Brazil, the country hardest hit by the outbreak
Philadelphia has become the first big city in the US to place a tax on soda to tackle the obesity crisis
Average global temperatures startlingly higher than normal between March-May
Government study provides strongest evidence of cell phone health effects
The reason for the high-level threat in the area is the presence there of Aedes aegypti mosquitoes, which carry the Zika virus that health authorities say causes birth defects in newborns
Three-day African Utility Week conference begins in South African city of Cape Town
More than two thousand activists came together to close an opencast coal mine in Germany.
New federal rules unveiled on Thursday will tackle the release of the greenhouse gas methane from oil wells and equipment as part of an effort to fight climate change.
At least five reef islands in the remote Solomon Islands have been lost completely to sea level rise and coastal erosion
Heads of UN, Work Bank lay out vision to deal with climate change
Turkish environment minister signs historic agreement in New York against taking action against climate change
Human defense mechanisms could be disrupted by the presence of a class of organic pollutants in fish and other food, according to new research.
'The time has come to treat childhood stunting as a development and an economic emergency,' World Bank Group head says