Hope On The Horizon?

A new diabetes drug shows great promise for treating Parkinson’s and Alzheimer’s diseases.

A diagnosis of Parkinson’s or Alzheimer’s disease can be devastating. Both these neurodegenerative diseases involve the death of vital brain cells, and at the present time, neither has a known cure. Even the cause for either disease is unknown, but the end result is the same: progressive loss of physical and mental capabilities and eventual death.

These diseases have many differences but also have some basic similarities that have led researchers to seek a common treatment for both diseases. But the complexity of neurodegenerative diseases has made this a daunting task. Much like the search for a cure to cancer, researchers have cast a wide net, looking for answers in virtually every branch of science while leaving no stone unturned. The pharmaceutical industry, using vital research from each of these branches, is investing billions of dollars into the search for a cure.

What Is Parkinson’s Disease?

Parkinson’s disease is a nonfatal progressive neurological illness caused by the death of dopamine-producing brain cells. Dopamine is a chemical neurotransmitter that carries “messages” between different parts of the brain, ensuring smooth, controlled muscle movement. As the dopamine-producing brain cells die, there is less dopamine in the brain and smooth muscle movement diminishes. The disease is characterized by tremors, stiffness and slowing of all physical movement. Many people with Parkinson’s also develop cognitive disorders, such as dementia as the disease progresses.

Researchers have no idea what causes the dopamine-producing brain cells to begin dying, and they have no idea how to stop them from continuing to die once the process starts. No present treatment can halt or even slow the progression of the disease.

Presently, the primary treatment for Parkinson’s is the oral medication L-DOPA, or levodopa. Levodopa is turned into dopamine once it enters the brain, thereby replenishing diminished dopamine levels. The problem is that levodopa therapy is fraught with side effects, one of which is dyskinesia. Dyskinesia is the abnormal and involuntary movements many times seen in Parkinson’s patients.

What Is Alzheimer’s Disease?

Alzheimer’s disease is a fatal neurological illness caused by the formation of protein-based plaques and tangles in the brain that leads to overall cell death and brain shrinkage. Here, cell death is widespread and not confined to just dopamine-producing neurons. The cause of the formation of these protein-based plaques and tangles is not known.

Scientists believe that clusters of tangles inhibit messaging between neural cells and, in many instances, triggers inflammation, which then causes the body’s own immune system to kill the disabled brain cells.

Whereas Parkinson’s affects motor activity first and then may lead to cognitive disorders, Alzheimer’s affects cognitive status first and then leads to motor skill degeneration. Present treatment involves drugs that boost the presence of neurotransmitters in the brain. This type of treatment may slow the symptomatic progression of the disease but cannot stop the disease itself.

Seeking A Cure: Multi-Targeted Therapeutics

It is standard practice in the pharmaceutical industry for companies to test drugs created to treat certain specific diseases in an effort to determine if they might also be of benefit in preventing or curing other diseases. This is called multi-targeted therapeutics, and in some instances, this practice has been highly successful. One drug that immediately comes to mind is the erectile dysfunction drug Viagra that was initially produced by Pfizer to help treat cardiovascular disease and pulmonary arterial hypertension. Today, Viagra is used to treat both hypertension and erectile dysfunction successfully and is one of Pfizer’s top-selling drugs.

Recently, a drug developed by Metabolic Solutions Development Company in Kalamazoo, Michigan, to treat type 2 diabetes has proven that it too may very well have alternative uses. Early research has shown that the drug MSDC-1060, a next generation insulin sensitizer, could either be, or lead to, a potential cure for both Parkinson’s and Alzheimer’s.

How It Works

MSDC-0160 inhibits the activity of a protein named mitochondrial pyruvate carrier (MPC). This protein’s function is to carry the molecule pyruvate into the mitochondria of each cell in the body. Once inside the mitochondria, pyruvate is turned into glucose, which is then used to power the cell.

MPC also has many other functions, one of which is to help control mTOR, a substance that controls cell growth and metabolism. Researchers believe that an overabundance of mTOR activity in Parkinson’s patients leads to a lack of communication between neurons and is one of the primary causes of cell dysfunction and many of the disease’s symptoms. As MSDC-1060 lowers the activity level of MPC, it concomitantly lowers the activity level of mTOR, and the end result is increased neural communication and a lessening of Parkinson’s symptoms.

MSDC-0160 therapy may also aid in the treatment of levodopa-induced dyskinesia. Researchers have found that an over activity of mTOR is a definite causative agent of this type of dyskinesia and believe that the drug will help alleviate such symptoms. Pre-clinical trials have shown that MSDC-0160 decreases levodopa-induced dyskinesia, and clinical trials are now being undertaken to determine the effectiveness for actual Parkinson’s patients. If trials prove the drug to be effective, then Parkinson’s treatment with levodopa would be greatly enhanced.

MSDC-0160 also helps treat neurodegenerative diseases in another way. An abundance of pyruvate, which is digested by the cell, means an abundance of cell waste. This waste is usually taken care of by the body in a natural process called autophagy. In Alzheimer’s and Parkinson’s patients, autophagy is greatly diminished and waste materials collect, adversely affecting overall cell health and encouraging inflammation. Research shows that autophagy increases as mTOR activity decreases, so when MSDC-1060 inhibits MPC activity (and thereby decreases mTOR activity), it helps increase autophagy and aids cells in getting rid of unwanted waste materials naturally. Reduced inflammation in the brain reduces the body’s immune response and, therefore, reduces cell death.

MSDC-0160 also has the ability to “protect” neural cells against genetic or environmental damage. In the laboratory, dopamine-producing cells are protected when the drug is introduced and they no longer continue to die in Parkinson’s pre-clinical models. The brain cells affected by the plaques and tangles in Alzheimer’s patients are also protected. This could be the most important aspect of the drug’s possible ability to aid in the treatment of Parkinson’s and Alzheimer’s—it may have the ability to slow or even stop cell death.

Help Is On The Way

MSDC-0160 is presently in clinical trials for the treatment of diabetes and Alzheimer’s disease. A multi-center, 12-week, phase 2 trial conducted by Metabolic Solutions and coordinated by Medpace showed very promising results in the treatment of type 2 diabetes. During the study, patients received an oral, once-a-day dose of the medication, with “no safety concerns” noted. Blood sugar levels were lowered significantly, and further study is underway.

As for Alzheimer’s tests, they show that MSDC-0160 possibly has the ability to help the ailing brain maintain glucose levels in certain areas of the brain that would normally diminish as the disease advances. Further studies are scheduled.

Pre-clinical evidence for the use of MSDC-0160 to be a major player in the fight against Parkinson’s and Alzheimer’s is promising. MSDC-0160 seems to have the ability to improve communication between neural cells, assist in the natural removal of cellular waste, lower mTOR levels (which should decrease levodopa-induced dyskinesia) and has the ability to protect neural cells from genetic or environmental damage. These results are now being used to design studies that will determine if this drug, or this class of drugs, might just be, or lead to, the eventual cure for Parkinson’s and Alzheimer’s diseases and other neurodegenerative disorders.

Sources: alz.org, mayoclinic.org, msdrx.com, onlinelibrary.wiley.com

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