Drug Compound Attacks Parkinson's Disease On Two Fronts

Date: Jun-20-2013A "dual inhibitor" - two compounds in a single molecule - was found to attack a pair of proteins linked to the development of Parkinson's disease, researchers from the Scripps Research Institute, Florida, reported in the journal ACS Chemical Biology.

Study leader, Professor Phil LoGrasso explained that the two proteins (enzymes) tend to amply each others' effect. "What we were looking for is a high-affinity, high-selectivity treatment that is additive or synergistic in its effect - a one-two punch."

The scientists believe that is exactly what they have found - a one-two punch.

The new dual inhibitor attacks two enzymes - JNK (c-jun-N-terminal kinase) and LRRK2 (leucine-rich repeat kinase 2).

After testing many thousands of Parkinson's patients, those with mutations in the LRRK2 gene had a much higher risk of developing Parkinson's disease. On the other hand, JNK plays a major role in nerve cell (neuron) survival in several neurodegenerative diseases. Hence, they have become popular targets for medications to treat Parkinson's disease and other neurodegenerative disorders.

A dual inhibitor, i.e. one with both HNK and LRRK2 inhibitors, is more preferable to having two separate medications because there would be no risk of drug-drug interactions, as well as having to adjust individual inhibitor doses for best efficacy.

The scientists now need to optimize the dual inhibitor for bioavailability, potency, and high selectivity so that the risk of off-target side effects are kept to a minimum. Then it will be tested on animal models of Parkinson's disease.

This study was supported by the National Institutes of Health grant NS057153.

A group of scientists found that increased iron levels may be casually linked to a lower risk of developing Parkinson's disease.

Researchers from Pavia and Milan, both in Italy, suggest that exposure to solvents and pesticides is associated with a higher risk of developing Parkinson's disease.
What is Parkinson's disease
Parkinson's disease is a progressive nervous system disorder, and belongs to a group of conditions called movement disorders. The disease is the result of the loss of dopamine-producing brain cells. Parkinson's affects how the patient moves, including how he/she writes and speaks.

Parkinson's signs and symptoms develop gradually over time, and might start with very slight and subtle tremors in one hand. Patients also experience stiffness and notice they cannot do things (movements) as fast as they used to - this is known as bradykinesia.

The Parkinson patient's muscle get weaker. Many assume an unusual posture.

Almost 80 percent of the dopamine producing cells in the brain die before the first motor symptoms of Parkinson's disease start to appear.

The four primary signs and symptoms of Parkinson's disease include:
Tremor - trembling in the face, jaw, legs, arms and hands
Rigidity - stiffness in the arms, legs and trunk
Bradykinesia - slow movements
Unstable posture - impaired balance and/or poor coordination

Some patients may experience cognitive changes, swallowing and chewing difficulties, constipation, urinary problems, skin problems, and disordered sleeping. As symptoms progress, walking, talking and completing other simple tasks become more challenging.

More than one million Americans are thought to live with Parkinson's; over 60,000 people are diagnosed with the disease every year. However, when taking into account those who go undetected, the figures are probably much higher.

According to Parkinson's Action Network, the economic burden of Parkinson's disease on families is enormous - $8.1 billion in medical expenses and $6.3 billion in indirect costs attributed to the disease.

Written by Christian Nordqvist

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