Functional and physiological effects of treadmill training induced by buspirone, carbidopa, and L-DOPA in clenbuterol-treated paraplegic mice.

Ung RV, Rouleau P, Guertin PA.
Laval University Medical Center (CHUL-CHUQ), Québec City, Québec, Canada.
Neurorehabil Neural Repair. 2012 May;26(4):385-94. doi: 10.1177/1545968311427042. Epub 2011 Dec 9.
Abstract

BACKGROUND:
Chronic spinal cord injury may be complicated by weight loss, muscle atrophy, and bone loss.

OBJECTIVE:
The authors identified a combination pharmacotherapy using buspirone, carbidopa, and L-DOPA (BCD) that elicits bouts of locomotor-like movements in spinal cord-transected (Tx) mice. They then evaluated the effects of 8 weeks of treadmill training in Tx mice that received BCD or BCD + clenbuterol, a monoaminergic agent with anabolic properties, on locomotor function, muscle atrophy, adipose tissue loss, and bone density measures.

METHODS:
Induced locomotor movement, adipose tissue, skeletal muscle, and femoral bone properties were compared in unoperated control mice, operated controls (untreated, untrained Tx mice), and 2 groups of treated, trained Tx mice (Tx + BCD, Tx + BCD + clenbuterol) that also received training.

RESULTS:
BCD- and BCD + clenbuterol-treated mice showed comparable levels of locomotor movements that significantly improved over time. Soleus muscle mass and soleus and extensor digitorum longus cross-sectional area significantly increased in both groups of BCD-treated mice, with greater effects in BCD + clenbuterol-treated animals. Fiber type conversion, adipose tissues, bone mineral density, and content were reduced in all Tx groups compared with unoperated control mice.

CONCLUSION:
These findings suggest that locomotor movement and muscle properties can be restored to near-normal levels after several weeks of BCD treatment, regular training, and clenbuterol in completely paraplegic animals.

Citation: Guertin P (2012) Promising Novel Class of Drug Treatment in Clinical Development for Chronic Spinal Cord Injury. J Neurol Neurophysiol 3:e107. doi:10.4172/2155-9562.1000e107

No animal model ideally suited to investigate the development of comorbid problems in chronic SCI had been developed until recently [17-21]. In fact, we have been the first group to have recently developed a model of chronic SCI in which systemic and metabolic problems were thoroughly characterized [22]. In parallel to these experiments, we also identified and developed a drug product aimed to prevent several of these chronic problems after SCI by activating pharmacologically a spinal locomotor network based in the lumbar area of the spinal cord [23-25]. This is the first and still the only drug treatment candidate in development for chronic SCI related health problems. The technology that is called SpinalonTM has undertaken in 2012 its first clinical trials in chronic SCI patients

Now, let’s only hope, after so many years of research in SCI, that this promising technology designed specifically for chronic SCI patients will succeed in moving along the difficult and risky path of clinical development. If eventually approved by regulatory authorities, may constitute in approximately five (5) years a novel class of safe and potent drug treatment for SCI patients.

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