POLL: Would you take Pagoclone?

Here is TheStutteringBrain's first poll. Pagoclone is a medication that seems to reduce stuttering according to Phase II trials. Please only take the poll if you stutter! Thx to Diego for the tip! You can leave more elaborate comments on the comments page.

Phase III of Pagoclone trials decided

This decision brings us as close as never before to a medication specifically approved to treat stuttering. Congratulations to Jerry Maguire and his team. Also, thx to Alessandro for the tip!

Indevus Announces Clinical and Regulatory Plans for Pagoclone

Company to Move Forward in Phase III Trials in Stuttering

Future Work on Premature Ejaculation Not Planned After Interim Analysis of Phase II Trial Showed Insufficient Efficacy

LEXINGTON, Mass.--Indevus Pharmaceuticals today announced that following an End of Phase II meeting with the FDA, the Company has established a clinical plan towards regulatory approval of pagoclone for the treatment of persistent developmental stuttering (PDS) and will initiate a Phase III trial in the first half of 2007. Separately, following an interim analysis of the Company’s Phase II trial of pagoclone in premature ejaculation (PE), the Company has chosen to discontinue the trial due to insufficient efficacy.

See more here.

Big $$$$$ for Indevus?

I estimate a 1bn dollar annual market for a stuttering medication.

Assume that 1% of the population stutters,
1bn people have access and can afford the medication,
10% of them would take it, and
the annual costs for the medication is around 1000$ (80$ per month).

That gives us 10 million people who could afford and have access to it, and 1 million people who would take it, and 1000 million dollars income per year.

John Paskievich and his Unspeakable

At the BSA conference, I went to the screening of Unspeakable, a documentary by John Paskievich: you can see short videos on this website. John is a well-known documentary maker who made his way to the Cannes Festival: here is a list of his documentaries at IMDB. His movie is mostly about the social impact of stuttering from his personal experience and life. I really like the documentary for its clear and uncompromising view on what it can be like to be a person who stutters. A powerful movie to share our experiences and feelings with the general public.
However, when Unspeakable deals with causes of stuttering, he is adding ketchup to a chocolate cake. He puts forward his own opinion indirectly by interviewing Darrell Dodge on the causes of stuttering who is absolutely not representative of the research community, in fact he is not even part of the research community. Moreover, Dodge's theory of "stuttering as a self-inflicted disorder of speech, communication, and awareness" is not supported by evidence, but in fact I would argue that latest genetics research contradicts it. But, I have to be fair and say that I agree with many individual statements / insights on his website, but not with his general conclusions which just show to me that he never did research himself i.e. like the pope talking about sex! By not clearly sticking to his own experience and giving his view of why people stutter John does a colossal disservice to himself, Unspeakable, and the people whose experiences he wants to get across.

Thinking in terms of circuit

Suddenly, many new ideas are popping up in my brain and floating around. Here is No 1: I noticed that I should probably think more in terms of circuits being dysfunctional rather than separate brain modules. The big advantage is that this more "system" (as opposed to local) way of thinking allows me to state that "The cause of stuttering is a defect somewhere in circuit X" rather than "For some, brain region A is not working well, in others the fibers connecting to region A and B are not well insulated". It might well be that stuttering occurs if any of the regions or fibers connecting the regions WITHIN a circuit is malfunctioning. So the goal should be to single out the circuit. So there might be a unifying way of encompassing all people who stutter, and difference can be explained by subtleties coming from where in the circuit the malfunctioning happens.

An interesting side product of this way of thinking is that there is a more natural way of asking why people with PDS seem to have inferior dual task performance. You can ask what is the region(s) that both dual-task circuit and stuttering circuit share. This would also lead to the conclusion that not all people with PDS should have inferior dual-task performances, as the stuttering circuit will NOT share all the same regions as the dual task circuit. So I would predict that only a subset of people with PDS would have inferior dual task performance i.e. only those that have a malfunctioning region / fibre, that also lies on the dual task circuit, in the stuttering circuit.

What I forgot to say at the conference

As you can see from the picture, I am moving too fast! The main theme of my brief talk was that the ability to study (and therefore to understand better) the brain has moved stuttering research in new territory. This is also the main theme of my blog. What I forgot to do is to explain why.

Ten years ago, you could formulate nearly every type of theory: a left-right conflict in the brain, the amygdala is overactive, the motor coding doesnt work well, and so on. Actually, my favourite theory is that little demon (probably female) getting drunk on occasionally tripping on the pathways that deliver the go-speak signal to the motor cortex. It is very different nowadays: If you support a theory, you need to explain all the new experimental evidence, for example:

1. Can your theory explain the genetic component?
2. If your theory focuses on a specific brain region, why doesnt it show up in brain imaging scans?
3. Why does this drug reduce stuttering?

So finally at last, you cannot just go about and say anything you like. You can still go and write about it, but you can no longer claim that you are doing research or science.

That is the real progress that is being made. It is still some way of, but theory building getting more constructive due to experimental constraints.

Zeitgeist of the BSA conference

Here are some general ideas floating around at the conference or in my brain during the conference:

1) over the last decade, more and more experimental findings are starting to constrain any theory building. Ten years ago, you could have said pretty much everything about what is happening inside the brain, but nowadays you need to face up with evidence that needs to fit your theory; a situation that many "researchers" find difficult to handle!!!!

2) there is definitely a genetic component to stuttering, but not a single gene.

3) stuttering is likely to be hetero-causal i.e. different causes lead to stuttering but on the same circuit.

4) genetic tests are going on and we should expect more research news happening. Dryana collected blood samples for his research. He run out of needles, so there was a great willingness to donate blood!

5) having a research session attached to the BSA conference worked well, and was a very cheap way of organising a mini research conference.

6) stuttering research is becoming more and more of a real science.

7) the Pagoclone study has still not published their results fully.

8) the researchers I invited seemed to have genuinely enjoyed the cross-disciplinary debate.

More soon. I have to go to Oxford to pick up my back pack that I forgot on the train. I hope it's mine!!!

Successful BSA conference.

I just came back from the BSA conference in Telford. The research section that I organised went extremely well. Everyone seemed very happy with the talks and the workshop. Dennis Dryana got many volunteers to donate blood for genetics research; he even run out of needles.

I am currently in London, and I am busy trying to get back my back pack that I lost yesterday on the train from Oxford to Reading, if you found it, let me know!! If you stole it, may god bless you with eternal stuttering! :-)

I'll update you on Wednesday evening about the conference talks. The picture of what stuttering is about is getting clearer in my view.

The new sciences of stuttering

I still have problems. But here is the first part of the description of research program at the Telford conference.

The new sciences of stammering

Over the last decade, advances in brain imaging, genetics, and pharmacology have provoked a revolution in the scientific understanding of the human brain. Scientists are now using this knowledge combined with the new research tools to tackle an age-long mystery: the mechanism and causes of stammering, and how best
to treat stammering. The BSA has invited to its annual conference in Telford leading researchers in the fields of neuroscience, genetics, and pharmacology to share with us the new sciences of stammering and answer the question: How are
neuroscience, pharmacology and genetics changing our understanding and treatment of stammering?

The main session of the program is the research plenary where leading researchers give conceptually clear and simple reviews of the progress made in their research area. After a tea break, the audience has the opportunity to ask probing questions to the panel or comment on any issues related to understanding or treating stuttering. The general sessions are followed by a research symposium where the experts will present and discuss cross-disciplinary topics.

For further information, please contact tom.weidig@physics.org
or visit the BSA website: www.stammering.org/conf.html.

Details of The New Sciences of Stuttering

Plenary
(Chair: Velda Osborne, Sat Sep 16th Sep 9:00-10:30)

Introducing the new sciences of stammering
(Tom Weidig)

The genetics of stuttering: a review
(Dennis Drayna, National Institute of Health, US)

The pharmacology of stuttering: a review
(Gerald Maguire, University of California at Irvine, US)

The brain and stuttering: a review
(Per Alm, University of Oxford)

Q&A sessions
(Chair: Tom Weidig, Sat Sep 16th 11:00-12:00)

Panel consists of speakers plus Kate Watkins, and LouiseWright.


Symposium
(Chair: Tom Weidig, Sat Sep 16th 14:00-17:30)

Given a gene, what is its function? Given a function, what is its gene? What if gene combinations make up a function? (Dennis Drayna)

Similarities and differences in the functional brain abnormalities associated with developmental stuttering and with a mutation in the FOXP2 gene. (Kate Watkins)

What does a medication-induced reduction in stuttering tell us about physiology and genetics of stuttering? (Gerald Maguire)

Is the dopamine D2 receptor important for genetic childhood stuttering? Neurological incidents and subgrouping. (Per Alm)

The measurement problem in stammering: a cross-disciplinary Pandora's box. (additional workshop on Sunday morning)

Main speakers of plenary

Dr. Gerald Maguire is Associate Professor at the Department of Psychiatry at the University of California, Irvine. He is a member of the US national stuttering association (NSA) and currently serves on its research advisory board. As a person who stutters himself, he has been interested in investigating novel treatments for stuttering since early in his medical training. His research group was the first to investigate brain differences in stutterers using the PET brain imaging method. He was the lead investigator on many studies investigating medications for the treatment of stuttering. At the Telford BSA conference, he will also talk about the latest trial on Pagoclone. Dr Maguire has spoken at a wide range of conferences like NSA, World Congress of Stuttering and ASHA. His research appeared at news outlets like the LA Times, NPR, ABC News, and the Boston Globe.

Dr. Dennis Drayna is a senior researcher in genetics at the National Institutes of Health in Bethesda, Maryland, where he currently serves as a Section Chief in the National Institute on Deafness and Other Communication Disorders. His primary research interests are the genetics of human communication disorders, work that has taken him to eight different countries on four continents in pursuit of families with these disorders. For example, he collected blood samples from an extended Pakistani family where many of its members stutter. At the Telford BSA conference, Dr. Drayna will discuss his latest research, and also collect blood samples from volunteers for his research work. He did a PhD at Harvard University, worked as a postdoctoral fellowship in the Howard Hughes Medical Institute at the University of Utah, and then spent 14 years in the biotechnology industry in the San Francisco Bay area.

Main Speakers of Plenary

Dr. Per Alm is a researcher at the University of Oxford, and works together with Dr. Kate Watkins on a project to understand the relationship between stuttering and brain functions. As a person who stutters he got involved in work on stuttering through the Swedish Stuttering Association. Having worked as an engineer in his previous life, he decided to take on stuttering, and go back to university to study neurosciences. He recently finished his PhD thesis on the causal mechanisms of stuttering at Lund University, Sweden. His attempts to combine a wide range of findings to a neurological model of stuttering have been well-received. He has especially emphasized the role of the brain structures called the basal ganglia. At the Telford BSA conference, Dr. Alm will discuss how the current understanding of the brain may help us understand stuttering.

I still have problems

I still have problems publishing... sorry

The blog works again.

That is typical. I write a comment that the blog doesnt work anymore, and the next second the blog works again!! I swear that it hadnt worked for 4 days at least! :-)