Doxycycline fights cell death and lessens disease severity in Merosin-deficient mice

Dr. Miller shows doxycycline, an antibiotic, improves lifespan, muscle strength/function and pathology in merosin deficient mouse model.

What is this research about?

In this study, Dr. Jeffrey Miller looked at the effect of giving mice with merosin deficient CMD a commonly used antibiotic, called doxycycline.  Merosin deficient CMD and UCMD are the two most common CMD subtypes.  Prior studies carried out by Dr. Miller and others had shown improvement in the merosin deficient mouse when treated with drugs that target apoptosis (look at prior reports with cyclosporine, debio 025 and omigapil).  Apoptosis is programmed cell death.  The mechanism between a lack of merosin and the apoptotic trigger has not been worked out. 

 

How did Dr. Miller carry out the experiment?

Dr. Miller put the merosin deficient mice into two groups.  The onset of muscle weakness and survival has been worked out in several merosin deficient mouse models.  One group received doxycycline in their drinking water starting 1-3 days after birth, while the other group did not receive doxycycline in their drinking water. 

 

What were the results?

The merosin deficient mice who received doxycycline in their drinking water showed the following improvements:

  • Improved life span: half the treated mice were still alive at 70 days after birth, while in the untreated group, half had died at about 32 days.
  • Increased weight: at 3 ½ weeks after birth, the treated mice weighed 30-40% more than untreated mice.
  • Improved paralysis: at 10-12 weeks after birth, the treated mice didn’t have back limb paralysis characteristically seen in the untreated mice at 4-6 wks after birth
  • Improved ability to stand on hind legs: at 6 weeks, treated mice stood on their hind legs about as often as mice with normal merosin levels, while untreated mice did this less than 1/3 as often.
  • Improved muscle histology: muscle of treated mice showed less inflammation and fewer indicators of apoptotic cell death than untreated mice.

 

What is doxycycline?

Doxycycline is a commonly prescribed antibiotic, used to treat a variety of infections from pneumonia to urinary tract infections in individual over the age of 8.  Doxycycline is indicated in infants and children less than 8 years of age only for the treatment of infectious diseases where no other alternative exists and the benefit of infectious cure outweighs the side effects listed below (anthrax, typhus, Rocky Moutain spotted fever). Doxycycline is not recommended in infants and children less than 8, because it causes discoloration of the teeth (yellow/brown or gray).  It also forms stable calcium complexes and may decreased bone growth and development.

 

Why is this study important?

  1. It helps validate prior studies in the merosin deficient mouse model that showed improvement in muscle strength and survival with a completely different set of drugs.
  2. It uses a drug that is already commonly prescribed in children above the age of 8 with pediatric formulation available.
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  • Congenital Muscular Dystrophy

    A group of diseases causing muscle weakness at birth. Several defined genetic mutations cause muscles to break down faster than they can repair or grow. A child with CMD may have various neurological or physical impairments. Some children never gain the ability to walk, while others lose the ability as they grow older. Learn more...

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