Hope for preventing dyskinesia

New Strategy Reduces Side Effects in Parkinson’s Treatment

December 10, 2015

Uncontrolled movements dramatically reduced with novel drug lead

CHICAGO — In an international study, Northwestern Medicine scientists and colleagues have identified a novel strategy for reducing the side effects of uncontrolled movement caused by the drug levodopa, commonly used to treat the stiffness, tremors and poor muscle control of Parkinson’s disease.

These unwanted movements caused by levodopa significantly diminish the quality of life for Parkinson’s disease patients.

A team lead by D. James Surmeier found neurons in the brain responsible for the side effects have a distinctive surface receptor that normally helps balance the effects of levodopa treatment. When mouse or primate models of Parkinson’s disease were given a compound that boosts functioning of this receptor, the uncontrolled motor side effects of levodopa treatment were dramatically reduced.

Surmeier is the Nathan Smith Davis Professor and chair of physiology at Northwestern University Feinberg School of Medicine.

The study was published Nov. 18 in the journal Neuron.

Although this new compound — an M4 muscarinic receptor positive allosteric modulator — is not currently approved for human use, it is in development with the goal of clinical trials, a Phase I trial possibly starting by 2017.

“There has been an international effort to find a drug that can be combined with levodopa to reduce the uncontrolled movement,” Surmeier said. “If clinical trials confirm our preliminary findings, the eventual drug developed could make a significant improvement in the quality of life for people with Parkinson’s disease.”

Parkinson’s is the second most common neurodegenerative disease in the U.S., affecting more than a million people, a number expected to double by 2030. In its early stages, the primary symptom of the disease — difficulty moving — can be effectively treated by levodopa.

5 Replies

  • Promising but early days yet.

  • A perspective. In my youth, one of the most frightening things I witnessed was a local resident with with severe dyskinesia, it was clearly awful. When, I was diagnosed, I had a flashback, my first thought was some thing much stronger than "darn". The when I told a good friend about my diagnosis, he told of his father's experience with PD, and how when levodopa became available it had made all the difference to him.

    Years passed by, gait disorder became a problem. Finally joined those medicated with levodopa, but it was combined with carbodopa (something about preventing dyskinesa?) Try talking to your Neurologist about that. Jest of the conversation., went something like this, PD is not a disease in the sense one gets measles. Rather, it is a collection of 20 or more symptoms. Diagnosis if a function of certain symptoms. Got a tremor, walk slow, don't swing one of your arms, you are in. Yet the particular symptoms that you end up with will be a unique set of those possible. They have a descriptive word for this. Seems like they use "ideopathic". The ideal being as I understand it, that each of us end up with a different set of symptoms. This includes how the symptoms are expressed. We are unique! Conversations with doctors have gone like this....will this dose of levodopa help my gait, lead to dyskensia? Helps some, does't help others, some get side effects, others don't. What about me????? PD is ideopathic, dose may help or may not. Taking more levodopa is a matter of looking at risk benefit. Your body, you decide. It is a gamble. Bu t doc, I don't even know how to play poker?

    Finally realized that it was time for myself to get a handle on what was going on, and see what I could do for myself. This lead me to"The Parkinson's Handbook" by Dwight McGoon MD (a PWP). "essential effect of PD is the interference with the coordination in the stratum of instructions that are normally delivered to muscles........it is a result of an impairment in the muscular tension (or pull) extensor joint muscles, which impairs the body's ability to stand up against the force of gravity."

    "Parkinson's Disease does not directly injure the muscles. ....the damage is secondary a result of the improper function. of the muscles. It is important that we minimize and prevent these harmful secondary effects. To allow, through our negligence, a joint to become stiff or muscles to shrink or scar down, and atrophy would prematurely add to pain, immobility and misery."

    "It is obvious, then, that every attention should be directed to preserving free mobility

    of the joints, maintaining muscle substance, and combating the effect of gravitational forces on posture."

    Question for each of us.....how is our attention to the obvious?

    Back to my choice about increasing levodopa.....decided risk too great, am focusing on obvious, ding better.


  • I thought Ideopathic meant they didn't know the cause of the desease. Not trying to correct you, maybe there are more than one definition. Thanks for writing, it was interesting.

  • Parkinson's disease

    From Wikipedia, the free encyclopedia

    "Parkinson's" redirects here. For other uses, see Parkinson's (disambiguation).

    Parkinson's disease (PD, also known as idiopathic or primary parkinsonism, hypokinetic rigid syndrome, or paralysis agitans) is a degenerative disorder of thecentral nervous system mainly affecting the motor system. The motor symptoms of Parkinson's disease result from the death of dopamine-generating cells in thesubstantia nigra, a region of the midbrain. The causes of this cell death are poorly understood. Early in the course of the disease, the most obvious symptoms aremovement-related; these include shaking, rigidity, slowness of movement and difficulty with walking and gait. Later, thinking and behavioral problems may arise, withdementia commonly occurring in the advanced stages of the disease, and depression is the most common psychiatric symptom. Other symptoms include sensory, sleepand emotional problems. Parkinson's disease is more common in older people, with most cases occurring after the age of 50; when it is seen in young adults, it is called young onset PD

    The word should be idiopathic, not ideopathic. The point being as it was explained to me, is that cases are not expressed a like in

    symptoms, so there is no comparison.

    Thank you for pointing out if I used an incorrect word. The point wanted to make is that each person's disease is unique, a drug treatment's effects are there fore not predictive.


  • That's always the depressing aspect of any new hope: phase I trials should be ready to start 2017. And then there's 10 years messing around after that. It'd be funny if it wasn't so disappointing.

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