Biomarkers identified for Lou Gehrig’s disease.

Researchers from the Rita Levi Montalcini Department of Neuroscience have identified blood biomarkers for Amyotrophic Lateral Sclerosis (ALS).  The team identified the blood biomarkers serum albumin and creatinine as being associated with survival in patients with amyotrophic lateral sclerosis (ALS) and state the findings may help define prognosis in patients after they are diagnosed with the fatal neurodegenerative disorder commonly known as Lou Gehrig disease.

The median survival time of patients with ALS is 2 to 4 years from onset and 1 to 3 years from diagnosis. Therefore, there is an urgent need to identify reliable biomarkers of ALS progression for clinical practice and pharmacological trials.

The authors examined blood markers for ALS diagnosis in a population-based group of 712 patients in Italy and then replicated the findings in another group of 122 patients from an ALS tertiary center. The protein blood markers examined included total leukocytes, glucose, cholesterol, albumin, creatinine and thyroid-stimulating hormones.  Creatinine is a chemical molecule that is present in the serum (liquid portion) of the blood generated from muscle metabolism.  The amount of creatinine the body produces each day depends on the person’s muscle mass.

Because muscle mass normally changes very little, creatinine is usually produced at the same rate every day. It ends up as a waste product in the blood that is transported to the kidneys. The kidneys maintain the blood creatinine in a normal range. Therefore, creatinine has been found to be a fairly reliable indicator of kidney function. Elevated creatinine level signifies impaired kidney function or kidney disease.  Thus if Cystatin C and radio-contrast CT prove kidney function to be a normal levels, creatinine levels could be a valid early indirect marker for ALS and a loss of muscle mass.

Albumin is a protein made by the liver, it is the most abundant protein present in mammalian plasma.  Lower-than-normal levels of serum albumin may be a sign of kidney diseases, and/or liver disease such as hepatitis, or cirrhosis.  Thus, if the aforementioned kidney functions tests are performed as well liver function tests; albumin could indicate ALS with transcapillary escape rate of albumin being measured. 

This is in standing with the 1978 Conradi study where the function of the capillary barrier in skeletal muscle was of interest in diseases of the lower motorneurons due to the uptake of noxious substances via the same route in ALS.  This in turn causes inflammation which lowers albumin levels by forcing the liver to divert some of its albumin production and make other proteins that are needed for the immune response.  For both the past and current study, albumin levels are seen as a good indirect marker of ALS.  ‘Normal’ levels of both markers must be determined for ALS stages and patients.

In the current study serum albumin and creatinine levels were related to ALS survival in both sexes. Creatinine reflected muscle waste and albumin was related to inflammation. Lower albumin and creatinine levels are related to worse clinical function at diagnosis.

The team state that both creatinine and albumin are reliable and easily detectable blood markers of the severity of motor dysfunction in ALS and could be used in defining patients’ prognosis at the time of diagnosis. Longitudinal studies on the variations in serum albumin and creatinine levels and their relationships to clinical status will help determine whether and how these hematological factors vary during the progression of the disease.

Source:  JAMA Neurology