Beyond the amyloid hypothesis: proteins that indicate cognitive stability

If you’re wondering where Alzheimer’s research might be headed after the latest large-scale failure of a clinical trial based on the “amyloid hypothesis,” check this Read more

Mother's milk is OK, even for the in-between babies

“Stop feeding him milk right away – just to be safe” was not what a new mother wanted to hear. The call came several days after Tamara Caspary gave birth to fraternal twins, a boy and a girl. She and husband David Katz were in the period of wonder and panic, both recovering and figuring out how to care for them. “A nurse called to ask how my son was doing,” says Caspary, a developmental Read more

Focus on mitochondria in schizophrenia research

Despite advances in genomics in recent years, schizophrenia remains one of the most complex challenges of both genetics and neuroscience. The chromosomal abnormality 22q11 deletion syndrome, also known as DiGeorge syndrome, offers a way in, since it is one of the strongest genetic risk factors for schizophrenia. Out of dozens of genes within the 22q11 deletion, several encode proteins found in mitochondria. A team of Emory scientists, led by cell biologist Victor Faundez, recently analyzed Read more

osteoporosis

Immune studies suggest remedies for parathyroid hormone-driven bone loss

A common cause of bone loss is an overactive parathyroid gland, which doctors usually treat with surgery. New research on how excess parathyroid hormone affects immune cells suggests that doctors could repurpose existing drugs to treat hyperparathyroidism without surgery.

The results were published October 8 in Cell Metabolism. [My apologies for not posting this in October.]

“Surgery is sometimes not an appropriate remedy for hyperparathyroidism because of the condition of the patient, and it is also expensive,” says lead author Roberto Pacifici, MD. “Also, the one pharmacological treatment that is available, cinacalcet, is not always the ideal solution. This work could potentially lead to alternatives.”

Roberto Pacifici, MD

Researchers at Emory University School of Medicine led by Pacifici teamed up with doctors from the University of Turin in Italy, combining observations of human patients with an overactive parathyroid with experiments on mice.

The drugs identified as potential treatments are: calcium channel blockers, now used to treat high blood pressure, and antibodies that block the inflammatory molecule IL-17A, under development for the skin disease psoriasis. Clinical trials would be necessary to show that these drugs are effective against parathyroid hormone-induced bone loss in humans. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Bone-strengthening particles stimulate autophagy

Neale Weitzmann and George Beck have been publishing a series of papers describing how silica nanoparticles can increase bone mineral density in animals. Their findings could someday form the basis for a treatment for osteoporosis.

In 2012, we posted an article and video on this topic. We wanted to call attention to a few of the team’s recent papers, one of which probes the mechanism for a remarkable phenomenon: how can very fine silica particles stimulate bone formation?

The particles’ properties seem to depend on their size: 50 nanometers wide – smaller than a HIV or influenza vision. In a 2014 ACS Nano paper, Beck, Weitzmann and postdoc Shin-Woo Ha show that the particles interact with particular proteins involved in the process of autophagy, a process of “self digestion” induced by stress.

“These studies suggest that it is not the material per se that stimulates autophagy but rather size or shape,” they write. Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

PTH for stroke: stem cells lite

I’d like to highlight a paper in PLOS One from anesthesiologists Shan Ping Yu and Ling Wei’s group that was published earlier this year. [Sorry for missing it then!] They are investigating potential therapies for stroke, long a frustrating area of clinical research. The “clot-busting” drug tPA remains the only FDA-approved therapy, despite decades of work on potential neuroprotective agents.

Yu’s team takes a different tactic. They seek to bolster the brain’s recovery powers after stroke by mobilizing endogenous progenitor cells. I will call this approach “stem cells lite.”

journal.pone.0087284.g006

PTH appears to encourage new neurons in recovery in a mouse model of ischemic stroke. Green = recent cell division, red = neuronal marker

It is similar to that taken by cardiologist Arshed Quyyumi and colleagues with peripheral artery disease: use a growth factor (GM-CSF), which is usually employed for another purpose, to get the body’s own regenerative agents to emerge from the bone marrow.

In this case, Yu’s team was using parathyroid hormone (PTH), which is an FDA-approved treatment for osteoporosis. They administered it, beginning one hour after loss of blood flow, in a mouse model of ischemic stroke. They found that daily treatment with PTH spurs production of endogenous regenerative factors in the stroke-affected area of the brain. They observed both increased new neuron formation and sensorimotor functional recovery. However, PTH does not pass through the blood-brain barrier and does not change the size of the stroke-affected area, the researchers found.

The conclusion of the paper hints at their next steps:

As this is the first report on this PTH therapy for ischemic stroke for the demonstration of the efficacy and feasibility, PTH treatment was initiated at 1 hr after stroke followed by repeated administrations for 6 days. We expect that even more delayed treatment of PTH, e.g. several hrs after stroke, can be beneficial in promoting chronic angiogenesis and other tissue repair processes. This possibility, however, remains to be further evaluated in a more translational investigation.

Posted on by Quinn Eastman in Neuro 1 Comment