Parkinson’s Disease Discovery Delivered in a Patch

2012-05-03 09:04

Parkinson’s disease is about loss: the loss of dopaminergic neurons that lead to a loss of motor control, as well as the loss of the ability to respond to the drugs used to treat this neurodegenerative disease. Now a discovery made by researchers at Tel Aviv University (TAU) could change this tradition of loss, and that change could be delivered in a patch.

Peptide patch could provide control

Parkinson’s disease, which affects more than 1 million Americans, is characterized by tremor, stiffness, impaired balanced, and slowed or frozen movements. These and other symptoms, such as mumbling speech, lack of facial expression, and not swinging the arms when walking, tend to worsen as the disease progresses.

The new discovery involved one of the recognized causes of Parkinson’s disease—gene mutation. Experts have found specific genetic mutations that appear to have a role in Parkinson’s disease. Gene mutations may be inherited or caused by various environmental exposures, such as cleaning chemicals, which are another proposed cause of the disorder.

Symptoms of Parkinson’s results from the lack of a chemical messenger in the brain called dopamine. Mutations of the gene DJ-1 can cause accelerated loss of dopamine-producing neurons. Investigators at Tel Aviv University have found a way to affect that loss.

Dr. Nirit Lev, a researcher at TAU’s Sackler Faculty of Medicine, and her team developed a peptide that mimics the normal function of DJ-1, which protects the dopamine-producing neurons. In tests, the peptide stopped neurodegeneration, reduced problems with movement and mobility, and resulted in higher levels of dopamine in the brain.

Treatments for Parkinson’s disease
Dr. Lev noted that “Current treatments [for Parkinson’s disease] are lacking because they can only address symptoms—there is nothing that can change or halt the disease. Until now, we have lacked tools for neuroprotection.”

Among the currently available drugs for treatment of Parkinson’s disease are the following:

  • Levodopa, which is converted to dopamine in the body. As the disease progresses, the benefits of levodopa may become less stable. Levodopa is taken with carbidopa, which protects levodopa from converting to dopamine too quickly.
  • Dopamine agonists (pramipexole, ropinirole), which mimic the effects of dopamine in the brain. These drugs can cause significant side effects, including hallucinations, low blood pressure, and the risk of engaging in compulsive behaviors.
  • Anticholinergics (e.g., benztropine, trihexyphenidyl), which help control the tremor but can also cause significant side effects.
  • Catechol O-methyltransferase inhibitors (e.g., tolcapone, entacapone) prolong the effect of carbidopa-levodopa but can also worsen levodopa side effects (entacapone) or cause liver problems (tolcapone).
  • Glutamate (NMDA) blocking drugs (amantadine) may provide short-term relief in early Parkinson’s or be helpful in later stages if carbidopa-levodopa causes involuntary movements

The new peptide in a patch
Dr. Lev and her team developed a peptide based on the healthy DJ-1 gene. They then attached the newly developed peptide to another peptide so it could be delivered to the cells and carried to the brain. The researchers say the new peptide can be given via injection or delivered through an adhesive patch.

In addition to serving as a treatment for Parkinson’s disease, the new peptide might also help prevent the disease. Dr. Lev noted that individuals with a genetic predisposition to Parkinson's disease may choose early testing, and that starting the peptide may help prevent development of the disorder.

SOURCES:
National Parkinson Foundation
Tel Aviv University

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