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Mutation Could Point to Tourette Treatment


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(Normally I just lurk here since I don't usually have anything worthwhile to contribute, but I was so excited to see this news today & I would love to hear what others think about it. I looked up histamine receptors in the CNS - H3 receptors - and everything connected to that relates to my son's problems! I had no idea that brain histamine affected levels of serotonin, dopamine, acetylcholine & norepinephrine. And the body uses methyl groups to convert histidine to histamine. It would explain why seasonal allergies & upper respiratory bugs send his tics & other issues into overdrive. While I doubt that my son has the genetic abnormality discussed in the article, I am wondering if he might have developed an autoimmune response to something related to the histamine pathway. Please let me know what you all think about this! ~Grace)

 

Mutation Could Point to Tourette Treatment

 

By AMY DOCKSER MARCUS

Researchers identified a rare genetic mutation that may open a new avenue for treating Tourette syndrome in a study published Wednesday that examined a family in which the father and all eight children suffer from the neurological disorder.

 

The family's mutation affected a gene required to produce histamine. Pharmaceutical companies are already developing drugs for other conditions that target the brain's histamine system. The study's researchers are planning a clinical trial of adults with Tourette to see if those drugs would help control the motor and vocal tics that characterize the condition.

 

Tourette syndrome is believed to affect 1% of the population. The condition is not life-threatening but can be debilitating. The tics, which can involve eye blinking, grunting and shouting, often appear initially in mid-childhood. Scientists don't know the disorder's cause but believe it has a strong genetic component.

 

Current treatments, such as the antipsychotic drug Haldol or the seizure drug Klonopin, are mainly used to control symptoms. But the drugs have side effects, including weight gain and drowsiness, and doctors said there was widespread recognition that better therapies were needed.

 

The study, published by the New England Journal of Medicine, said the gene mutation appeared to be very rare.

 

"It gives us a very critical window into at least one known genetic disruption that leads to Tourette syndrome," said Laura Mamounas, a program director at the National Institute of Neurological Disorders and Strokes in Bethesda, Md., which is funding Tourette research and is part of the National Institutes of Health.

 

The study, led by Matthew State, co-director of the Yale Program on Neurogenetics and an associate professor at Yale University School of Medicine, looked at a family in which the 47-year-old father and all eight children, ranging in ages from nine to 23, had been diagnosed with Tourette syndrome. The 45-year-old mother, her parents and members of her extended family did not have the disorder.

 

Dr. State's lab took DNA samples from all family members and was able to find one region of the genome that everyone with the disorder shared. By analyzing all 51 known genes in the region, the researchers identified a mutation in a gene required to produce histamine. Histamine plays a role in allergic reactions, but is also a neurotransmitter that influences brain functions, including sleep and cognition.

 

A 2009 paper in Drug Discovery Today cited efforts at pharmaceutical companies, including Abbott Laboratories and Pfizer Inc., to develop therapies to increase the release of brain histamine to treat conditions including Alzheimer's disease, sleep problems and schizophrenia.

 

Spokeswomen for both companies confirmed they have histamine compounds in clinical development. Regarding the drugs' possible use with Tourette, Melissa D. Brotz, a spokeswoman for Abbott, said the company "would evaluate potential research avenues as the science evolves."

 

Anabella Villalobos, Pfizer's interim head of neuroscience research, said the Tourette finding was intriguing, and the company was interested in learning about the planned study "and the role of histamine in the wider Tourette syndrome population.''

 

Lawrence Scahill, a professor of child psychiatry and nursing at Yale who treats people with Tourette syndrome, said he and Dr. State have applied for a grant to launch a two-year trial involving 20 adult patients. He said the Yale researchers were reaching out to a number of companies, which he declined to identify, to see if they could obtain histamine compounds to try with Tourette patients.

 

Kevin McNaught, vice president for medical and scientific programs at the Tourette Syndrome Association, a patient advocacy group that connected the family in the study to the Yale lab, said there are many continuing genetic-research projects, including a brain-tissue bank. The NIH is funding a project involving thousands of people with Tourette syndrome in an effort to find more common genetic variants that may cause the disorder.

 

One of the key questions the study raises is whether the findings will have implications beyond this one family and a small subset of people who eventually turn out to have this particular rare mutation or will provide a new therapeutic option for many people with the disorder. Yale's Dr. State said that after finding the mutation in the family, his team examined the DNA of 700 other people with Tourette syndrome to see if anyone else had the same mutation "and we couldn't find any.''

 

James Lupski, a professor of molecular genetics at Baylor College of Medicine in Houston, said that even if the mutation turns out to be very rare, the finding could have broad therapeutic implications because treatments developed to address it could apply to other mutations.

 

Write to Amy Dockser Marcus at amy.marcus@wsj.com

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welcome Grace :D and thanks for posting this info

 

It is also being discussed on our PANDAS forum where the comments may put it into perspective

http://www.latitudes.org/forums/index.php?showtopic=8095

 

Thank you, Chemar! I'll wander over & start catching up! :)

 

P.S. Thanks so much, too, for all the wonderful info you have provided here!

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Grace, I too find this exciting news. I am hopeful that it will lead to effective interventions that address a host of issues associated with TS.

 

I'm adding a couple of links to your discussion if you don't mind:

 

More on the original study in the NEJM > http://content.nejm.org/cgi/reprint/NEJMoa0907006v1.pdf

 

https://www.neurorelief.com/index.php?optio...8&Itemid=48

 

http://molinterv.aspetjournals.org/content/6/2/77.full (snip below)

 

Since the original description of the histamine H3 receptor as a presynaptic autoreceptor that inhibits histamine release (1), along with its subsequent recognition as a heteroreceptor that regulates the release of other important neurotransmitters, there has been considerable effort by both academic and industrial laboratories to develop potent and selective H3 receptor antagonists (Figure 1). Such antagonists are sought for the potential treatment of a variety of disorders affecting cognition (e.g., attention deficit and hyperactivity disorder [ADHD], Alzheimer’s disease, and schizophrenia), sleep (e.g., hypersomnia and narcolepsy), and energy homeostasis (e.g., obesity). The purpose of this paper is to review some of the preclinical considerations, including basic H3 receptor biology, as well as aspects of general drug discovery, that are relevant to the development of effective H3 receptor antagonists for the treatment of these diseases. In addition to the specific advances in H3 receptor antagonist research that we illustrate here, recent comprehensive reviews are highly recommended (2–5).

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Grace, I'm adding this to your post as well given I've recently felt that vitamin C has been a great help to my dd. I have not read this study in full, but plan to later. Below is an interesting snip.

 

http://selfdevelopmentedge.com/the-role-of...min-c-part-iii/

 

The contents of this dissertation have introduced a multidimensional model for the attenuation of histamine-related mental illness via vitamin C supplementation. Both histamine and vitamin C affect the human body on multiple levels. Histamine plays many different roles in the body, including neuromodulation, neurotransmission, allergic mediator, inflammatory mediator, and gastric acid secretion stimulator. When histamine levels are in the normal range, the above processes are usually in equilibrium and functioning optimally. It is when histamine levels become too low or high that trouble can arise. One of the roles of vitamin C in the body is to modulate histamine levels; if histamine levels are low, vitamin C administration will cause small amounts of histamine to be released. When histamine levels are abnormally high, vitamin C acts as an antihistamine, destroying excess histamine and thus bringing this chemical down to normal physiological levels.

 

Food for thought.

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