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Neurodegenerative Disease Treatment - Could the Diabetes Drug Help?
Drug Used in Diabetes Treatment Could Help in Neurodegenerative Disease Treatment

The big group of diseases known as leukodystrophies are described and known as progressive loss of the myelin sheath which is the fatty cover that acts as an insulator around nerve fibres. Damage of the myelin sheath blocks or make unstable the conduction of signals in the affected nerve fibres and leads to many severe locomotor problems.

There is no cure for neurodegenerative disease in presence. Various diseases such as Alzheimer’s, Parkinson’s and Huntington’s disease present huge problem for modern medicine, because drug used in these diseases treatment are not efficient, and they can only be used symptomatic.

Spanish scientists have done some experiments with a drug used to control diabetes type II. They have discovered recently that it can help healing of the mice spinal cords suffering from adrenoleukodystrophy disease, which, untreated, leads surely to a paralysis, a vegetative state and death of an organism. They are sure that their research results may be relevant to other neurodegenerative diseases. This drug is currently being tested in a clinical phase II.

The discovery of this drug is an important step in development of neurodegenerative diseases treatment. Current treatment options are very rare and they are just partially effective in treatment.

ABCD1 protein and peroxisomes

Researcher from the Neurometabolic Diseases Laboratory at IDIBELL, Barcelona, Spain, tried to reveal the role of mitochondria, special cell's organelle. This mitochondria, the power plant of the cell, had unknown role in adrenoleukodystrophy, a neurodegenerative disease provoked by the inactivation of the ABCD1 transporter. This transporter has transport function of fatty acids in peroxisomes. This process inactivation leads to the severe accumulation of fatty acids in human body. Mainly they are accumulated in organs and blood plasma, and these accumulations can cause degeneration of the spinal cord.

Mitochondrial role in adrenoleukodystrophy diseases

ABCD1 protein is a transport protein located in the peroxisomes. These peroxisomes are compartments of the cell that have function to detoxify chemicals and lipids, and because of that mitochondrial role in such a neurodegenerative disease was not obvious at all. But, beside that they didn’t know the role of mitochondria in neurodegenerative disease, researchers knew from latest research that oxidative stress role was involved in mitochondrial presence and influence. In human body, in organs or tissues with increased production of chemically active oxygen-containing molecules, there was obviously significant lack in the effectiveness of the body's antioxidant defenses, mitochondrial presence and involvement was present.

Scientists were also familiar with fact that bioenergetic failure appears to happen before symptoms of disease. Because of that and some more facts, they were determined to investigate the role of the mitochondria in neurodegenerative diseases.

Guidelines for research

Because scientists knew effects of oxidative stress damage and dysfunction of bioenergy are responsible for degeneration of nerve fibres, they began a study on mice. They used study on mouse model of X-linked adrenoleukodystrophy (X-ALD) , the most frequently inherited leukodystrophy. When they found good medium, they began to look at mitochondria for further clues. After that research, they found out that the X- linked adrenoleukodystrophy mice showed a loss of mitochondria at age of 12 months. This discovery wasn’t enough to reveal direct consequence of the disease, but it was enough to reveal that that mitochondrial loss could be a contributing factor. Scientists have discovered that mitochondrial loss could be possibly treated with one of frequently used drugs in diabetes disease. This drug, pioglitazone, has showed good results in mice with adrenoleukodystrophy disease treatment.

Pioglitazone adrenoleukodystrophy disease treatment mechanism

Pioglitazone drug is capable to stop the nerve fibre degeneration. This mechanism is based on prevention of the mitochondrial loss, and inhibiting oxidative stress and metabolic failure in the treated mice. Because of this mechanism locomotor disabilities could be prevented, or when started halted. The scientists are able to prove this through two ways. First way is to prove this through analysis of spinal cords post mortem, and second way is in vivo test. This in vivo test is obtained by putting the mice through a number of physical tests.

X- adrenoleukodystrophy is a pretty rare disease. It has minimum incidence of 1 in 17 000 males. But there are different neurodegenerative disorders caused by degeneration myelin sheath. The most frequent neurodegenerative disease is multiple sclerosis, but there are many other diseases where impaired bioenergetics combined with oxidative stress and axons degeneration are known to be involved. The other neurodegenerative diseases include Parkinson's, Huntington's, and Alzheimer's. Scientists from University of Barcelona will not be surprised if these findings appear to be relevant to these other neurodegenerative diseases as well.

Future expectations of Pioglitazone

According to these promising results, together with other researchers, scientists will shortly be starting a multi- centre phase II clinical trial. In this trial they will follow effects of pioglitazone in adult patients suffering from a late beginning of a variant of adrenoleukodystrophy. They are sure that it will be possible to monitor the biological effects of the drug by tracking the biomarkers of oxidative damage in plasma or blood cells. However, scientists are very happy to have made a huge contribution in finding an effective and, of course, very simple treatment to a very severe neurodegenerative diseases, and they are optimistic in way of new researches.


Neurodegenerative diseases are very severe diseases for human population. Loss of nerve fibres could be prevented or even stopped. This well known drug, pioglitazone, is possibly solution for those who suffer from neurodegenerative diseases. These research results are very good news for both doctors and patients with these neurodegenerative diseases. Even if it is still on clinical phase II trial, it is very certain that it will be a revolutionary discovery as soon as clinical trial ends. We can only expect that it is only the beginning of neurodegenerative diseases researches era.
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