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 publishedÂ October 8 inÂ Cell Metabolism. [My apologies for not posting thisÂ 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
I was struck by one part of Mirko Paiardini’s paper that was published this week in Journal of Clinical Investigation. It describes aÂ treatment aimed at repairing immune function in SIV-infected monkeys, with an eye toward helping people with HIV one day.Â One of the goals of their IL-21 treatment is to restoreÂ intestinal Th17 cells, which are depleted by viral infection.Â In this context, IL-21’s effect is anti-inflammatory.
However, Th17 cells are also involved in autoimmune disease. A recent Cell Metabolism paper from endocrinologist Roberto Pacifici and colleagues examinesÂ Th17 cells, with the goal of treating bone loss coming from an overactive parathyroid. In that situation, too many Th17 cells are bad and they need to be beaten back. Fortunately, bothÂ an inexpensive blood pressure medication and a drugÂ under development for psoriasisÂ seem to do just that.
Note for microbiome fans: connections between Th17 cells and intestinalÂ microbes (segmented filamentous bacteria) are strengthening. It gets complicated because gut microbiota, together with Th17 cells, mayÂ influenceÂ metabolic disease and Th17-like cells are also in the skin — location matters.
It is a privilege to work at Emory and learn about and report on so much quality biomedical research. I started to make a top 10 for 2014 and had too many favorites. After divertingÂ some of these topics into the 2015 crystal ball
,Â I corralledÂ them into themes.
1. Cardiac cell therapy
2. Mobilizing the body’s own regenerative potential
4. Parkinson’s disease therapeutic strategies
(Gary Miller, better packaging for dopamine could avoidÂ stress to neurons).
5. Personal genomics/exome sequencing
, likeÂ Emory’s Robert Gross
and Costas Hadjpanayis, do amazing things
7. Fun vsÂ no fun
Our Web expert
tells me this was Lab Land’s most widely read post last year.
9. Fine-tuning approaches to cancer
Iâ€™d like to highlight a paper in PLOS One from anesthesiologists Shan Ping Yu and Ling Weiâ€™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 â€œclot-bustingâ€ drug tPA remains the only FDA-approved therapy, despite decades of work on potential neuroprotective agents.
Yuâ€™s team takes a different tactic. They seek to bolster the brainâ€™s recovery powers after stroke by mobilizing endogenous progenitor cells. I will call this approach â€œstem cells lite.â€
PTH appears to encourage new neurons in recovery in a mouse model of ischemicÂ stroke. Green = recent cell division, red = neuronal marker
It is similar to that taken by cardiologistÂ Arshed Quyyumi and colleagues with peripheral artery disease: use a growthÂ factorÂ (GM-CSF), which is usually employed for another purpose, to get the bodyâ€™s own regenerative agents to emerge from the bone marrow.
In this case, Yuâ€™s team wasÂ 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 foundÂ that daily treatment with PTH spurs production of endogenousÂ 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.