A new Israeli-American study suggests there is hope of treating certain inborn congenital metabolic diseases, and that hope is a compound readily available in a cup of green tea or a glass of red wine.

Most people with inherited metabolic disorders are born with a defective gene that results in a critical enzyme deficiency. Because there’s no cure, they often have to adhere to a strict and demanding diet their entire lives.

That’s why this recently completed research study led by Prof. Ehud Gazit and his doctoral student Shira Shaham-Niv at Tel Aviv University is so promising. Their results were published in the Nature group journal Communications Chemistry.

The researchers considered two compounds: epigallocatechin gallate (EGCG), found naturally in green tea, which has attracted attention within the medical community for its potential health benefits; and tannic acid, found in red wine, which is known to prevent the formation of toxic amyloid structures that cause neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease.

“In the case of inborn congenital metabolic diseases, the body does not produce a vital metabolic enzyme,” Shaham-Niv said. “As a result, metabolites — substances that are, among other things, the building blocks of DNA and proteins — accumulate in the body. Such uncontrolled accumulation is toxic and can cause severe developmental and mental disorders.

“Our new study demonstrates once again the ability of nature to produce the best candidate of drugs to treat some of the worst human maladies.”

Collectively, this group of disorders constitutes a significant portion of pediatric genetic diseases.

The disease phenylketonuria (PKU), which produces the aggregation of the metabolite phenylalanine, is one common inborn metabolic disease. People born with PKU face severe debilitating developmental problems unless they steer clear of foods containing phenylalanine, including common sources of protein such as dairy products, meat, fish, chicken, eggs, beans and nuts.

“But this is an incredibly difficult task, since phenylalanine is found in most of the food products that we consume,” Shaham-Niv said. “The avoidance of certain substances is the only way to prevent the debilitating long-term effects of inborn congenital metabolic disorders. We hope that our new approach will facilitate the development of new drugs to treat these disorders.”

An overhaul in understanding metabolic diseases

The new research is based on two previous studies conducted at Gazit’s TAU laboratory. In the first study, phenylalanine was shown to be capable of self-assembly and of forming amyloid structures like those seen in Alzheimer’s, Parkinson’s and other neurodegenerative diseases.

In the second study, by Shaham-Niv, other metabolites that accumulate in other inborn congenital metabolic diseases were also shown to undergo self-assembly processes and form toxic amyloid aggregates.

“Both studies led to an overhaul in the research community’s understanding of metabolic diseases,” Shaham-Niv said. “In our new study, we examined whether the molecules identified in past studies on Alzheimer’s disease and other amyloid diseases, which are known to inhibit the formation of amyloid aggregates, could also help counteract the amyloid formation process of metabolites in metabolic diseases.”

In this study, EGCG and tannic acid were tested on three metabolites related to three innate metabolic diseases: adenine, cumulative tyrosine and phenylalanine. Both substances proved effective in blocking the formation of toxic amyloid structures.

The researchers also used computer simulations to verify the mechanism driving the compounds.

“We are entering a new era of understanding the role and the importance of metabolites in various diseases, including metabolic diseases, neurodegenerative diseases and even cancer,” Shaham-Niv concluded. “The tools we have developed are groundbreaking and have tremendous potential to help a wide range of patients in the future.”

Also participating in the study were scientists from the University of Illinois and the University of Texas.