Metformin Improves Alport Syndrome Survival Rate in Mice Models

Normally, metformin is used to help control blood sugar in patients with type 2 diabetes. However, new research suggests that the treatment option could also be beneficial for those with Alport syndrome, a rare genetic disorder characterized by progressive kidney function decline. According to News Medical, researchers from Kumamota University wanted to explore how metformin assisted those with non-diabetic chronic kidney disease (ND-CKD). Thus, using mice models of Alport syndrome to evaluate the drug’s effect on a syndrome under the general umbrella of ND-CKD seemed promising. Altogether, the data highlights how the treatment inhibits disease progression and increases overall survival rate. Check out the full findings published in Scientific Reports.

Metformin

According to MedLine Plus, metformin belongs to a class of drugs called biguanides, and works to help control glucose levels:

It decreases the amount of glucose you absorb from your food and the amount of glucose made by your liver. Metformin also increases your body’s response to insulin, a natural substance that controls the amount of glucose in the blood.

In prior research, metformin has:

  • Reduced, or protected against, inflammation and fibrosis (the formation of scar tissue)
  • Been an efficient and cost-effective treatment option
  • Improved renal function in patients with diabetic kidney disease

Thus, researchers questioned whether metformin could have the same protective effects in patients with ND-CKD, either as a monotherapy or in conjunction with another treatment. For example, combining losartan (a drug to help manage blood pressure) could be helpful when used alongside metformin.

Since ND-CKD does not have a lot of treatment options, many patients eventually end up on dialysis or requiring a kidney transplant. In patients with Alport syndrome, collagen abnormalities prevent adequate glomerular filtration. An estimated 50% of patients end up with renal failure before age 25, with nearly 90% of patients in kidney failure before age 40. Normally, blood pressure medication and other attempts to maintain kidney function are used. However, there is a clear unmet need within this patient population.

The Research

As a result, researchers decided to discover and identify new therapeutic targets for patients with Alport syndrome. To do this, they used mice models of the condition. During their research, researchers explored both metformin and losartan. After administering this treatment to the mice models, researchers discovered that:

  • Both treatments reduced proteinuria, or excessive protein levels in the urine. Additionally, the treatments suppressed/reduced serum creatinine. Typically, both proteinuria and serum creatinine are markers of chronic kidney disease.
  • Mice models saw improvements in kidney function, and reductions in both kidney inflammation and fibrosis, following treatment.
  • Metformin treatment altered (and improved) gene expression in relation to podocyte abnormalities and intracellular metabolism, making it slightly more targeted and effective than losartan treatment.
  • Using low doses of either metformin or losartan improved overall survival (OS) rates for mice models of Alport syndrome. If one therapy alone was not effective, using them in conjunction was effective.
  • Unfortunately, for patients with severe renal dysfunction, metformin should not be used. This is because, in this patient subgroup, metformin could cause lactic acidosis. Overall, lactic acidosis causes an overproduction of lactic acid, which can be damaging to both the liver and kidneys.

Alport Syndrome

Overall, COL4A3, COL4A4, and COL4A5 gene mutations cause Alport syndrome, a rare genetic disease which causes damage to blood vessels in the kidneys. Normally, these genes create type 4 collagen, which plays a role in kidney function and removing waste and water from the blood through glomeruli. However, if the glomeruli cannot effectively filter out this waste, blood and protein are excreted through urine. Ultimately, this causes kidney scarring and inflammation. Because type 4 collagen is also used in other areas of the body, those with Alport syndrome may experience hearing or vision difficulties. Males are more likely to develop severe symptoms than females. An estimated 1 in every 50,000 newborns is born with Alport syndrome.

Symptoms of Alport syndrome include:

  • Proteinuria
  • Bloody urine
  • Hypertension / high blood pressure
  • Abnormal inner ear structures
  • Fatigue
  • Appetite loss
  • Swelling of the eyes, ankles, feet, and legs
  • Hearing loss
  • Abnormal retinal coloration
  • End-stage renal progression
  • Excessive thirst
  • Frequent urination
  • Misshapen lenses in the eyes

Learn more about Alport syndrome.

Jessica Lynn

Jessica Lynn

Jessica Lynn has an educational background in writing and marketing. She firmly believes in the power of writing in amplifying voices, and looks forward to doing so for the rare disease community.

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