Antihypertensive agents from different classes significantly reduced beta-amyloid protein plaques in a mouse model of Alzheimer's disease. Also this week: a master gene for autoimmune disease.
Antihypertensives for Alzheimer's?
Certain antihypertensives have the unintended side effect of reducing the accumulation of beta-amyloid in the brains of mice with Alzheimer's disease, researchers found.
Giulio Maria Pasinetti, MD, PhD, of Mount Sinai School of Medicine in New York City, and colleagues screened 1,600 FDA-approved drugs to look for any that might have activity either inhibiting or promoting the formation of beta-amyloid. They identified 184 drugs that reduced levels of the protein by more than 30%, including 13 cardiovascular drugs.
Of those, seven antihypertensives in different classes -- carvedilol, propranolol, valsartan (Diovan), losartan, hydralazine, nicardipine, and amiloride -- provided concentration-dependent reductions of beta-amyloid in vitro.
Propranolol, nicardipine, and carvedilol were then given to mice with Alzheimer-like amyloid pathology. After 1 month of treatment, each drug reduced the amount of beta-amyloid in the animals' brains by about 40%.
"This line of investigation will lead to the identification of common medications that are potentially beneficial or detrimental to Alzheimer's disease as a reference for physicians to consider when prescribing the most appropriate drugs for their patients, particularly for treating chronic disorders among the growing geriatric population," the researchers wrote in PLoS ONE.
-- Todd Neale
Gene Oversees Immune Checks and Balances
Mutations in a single gene may be responsible for the immune disruptions that result in disparate conditions ranging from allergies to type 1 diabetes, lupus, and Crohn's disease, researchers from the National Institutes of Health reported.
The gene, BACH2, regulates the process by which T cells differentiate into either immune system activators -- spurring inflammation in response to external threats -- and immune system restrainers that put the brakes on those inflammatory processes when the threat has been eliminated.
Writing in Nature, the researchers, led by the scientific director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases, John O'Shea, MD, demonstrated that mice lacking BACH2 developed lethal autoimmune inflammation in the lungs and spleen within months of birth, along with autoantibodies similar to those found in patients with lupus.
They then found that replacing BACH2 in these knockout mice through gene therapy restored the normal immune balance, suggesting that this gene may be a suitable target for therapeutic manipulation.
-- Nancy Walsh
One Better Than Two in GVHD
Acute graft-versus-host disease, or GVHD, occurs after allogeneic transplant of hematopoietic stem cells because donor T cells, transplanted with the graft, attack the recipient's major histocompatibility complex antigens. But it has not been clear which T cells are responsible.
Now researchers led by Paul Allen, PhD, of Washington University in St. Louis, think they may have an answer: the culprit cells are the rare ones that have two T-cell receptors on their surface. Building on experiments in mice, they report in Science Translational Medicine that stem cell transplant patients with acute GVHD have significantly more such cells than do healthy controls or patients who didn't develop GVHD.
And such cells have pathologic activity in the test tube, they reported. Dual-receptor T cells from patients with acute GVHD significantly increased production of the inflammatory cytokines interferon-gamma and interleukin-17a, compared with dual-receptor cells from healthy controls or patients without GVHD.
-- Michael Smith
Naturalistic Model for Parkinson's Disease
Mice bred to overexpress a protein that drives progression of Parkinson's disease developed many of the age-related motor symptoms and changes in sleep seen in patients with Parkinson's disease.
The mice overproduced alpha-synuclein, the essential building block for the characteristic Lewy bodies that form in the nerves of humans with Parkinson's disease. As compared with normal mice, aging transgenic animals with a specific mutation of the alpha-synuclein gene developed progressively worse motor function on a standardized test.
The transgenic mice also exhibited fragmented nighttime behavior, consistent with disturbed sleep that occurs in many patients with Parkinson's disease. However, the animals did not exhibit signs of increased anxiety and depression that often affects patients.
Currently, most preclinical Parkinson's research is conducted in rodents injected with chemical toxins that destroy dopaminergic neurons, which reproduces the motor symptoms of the human disease but not its spontaneous onset, molecular pathology, or progressive course.
Though not a perfect mimic of human Parkinson's, the transgenic mice may prove useful in studying certain aspects of Parkinson's disease, Sarah M. Rothman, PhD, of the National Institute on Aging, and colleagues reported in the Journal of Parkinson's Disease.
-- Charles Bankhead
Sweetening T Cells to Fight Cancer
Giving a little sugar to T cells might enhance their ability to fight cancer cells, researchers reported.
When cancer cells consume much of the available sugar in the same dish as T cells, the latter are rendered impotent to make inflammatory, tumor-fighting compounds, said researchers at Washington University in St. Louis.
But when the researchers fortified the T cells with extra sugar, they produced twice as much of their inflammatory weaponry, according to a report in the June 6 edition of Cell.
"It's like an on-off switch, and all we need to do to flip it is change the availability of sugar," said lead researcher Erika Pearce, PhD, in a press release. "T cells often can go everywhere -- tumors, inflammation, infections -- but sometimes they don't do anything. If we can confirm that this same switch is involved in these failures in the body, we might be able to find a way to put the fight back into those T cells."
-- Kathleen Struck
