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Discussing treatments targeting TREM2 in Alzheimer’s disease subgroup of patients

MD-FM Thursday November 22, 2012




GENERIQUE
Carillon
 
Sarah :
MD FM — Medical News from around the the world with Peter Goodwin

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PETER: And with me is Sarah Maxwell. To begin with: As you might have heard last week, a rare mutation has been discovered, which drastically increases the risk of late-onset Alzheimer’s disease... and experts are already discussing the new therapeutic options that could stem from this discovery.

SARAH: This new mutation was discovered inside the TREM2 gene, which codes for an innate immune receptor involved in microglial signalling. The mutation is called R47H. Listen to Pr. John Hardy, from the University College London, who was one of the several experts involved in its discovery:

Bob Hardy: “It’s in about 0.2% of controls and about one percent of cases --So it’s quite rare. It’s not a direct causative gene, it’s a risk gene, but if you’ve got it, it increases your risks about 5-fold.”

SARAH: That was John Hardy, from the UK. His team then collaborated with several teams in the US, who performed genome wide associations and animal studies to confirm the association. The results are described in one of two studies published last week in the NEJM, the other comes from the deCODE group in Iceland, who came to similar conclusions.

PETER: So what are the prospects associated with these findings?

SARAH: Well first of all, all these experts say these findings will help us better understand the implication of the immune system in Alzheimer’s disease. The ultimate goal is obviously to develop new therapeutics. Again, listen to Dr. Hardy:

Bob Hardy: “The next step with regards to TREM2, I think –one of the next steps --and this was mentioned by the deCODE people too, is to get a drug which increases the activity of TREM2. I think it’s telling us that an anti-inflammatory drug that specifically targets TREM2 will be a good target for Alzheimer’s disease.”

SARAH: This was John Hardy, from London, who also said another avenue would be to look at TREM2 agonists to see if we can delay the onset of the disease --so in a preventative approach.


VIRGULE MUSICALE

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The positive effects of pallidal neurostimulation in patients with severe idiopathic dystonia were maintained 5 years after treatment. This is according to a study including 38 patients with primary, generalised or segmental dystonia, who underwent 6 months of neurostimulation. The results, published in The Lancet Oncology, reported significant improvements in dystonia severity at 3 years post-treatment, and remained practically unchanged at 5 years.


VIRGULE MUSICALE

P3
PETER: Endovascular repair and open surgery are similar in terms of long-term survival for patient with asymptomatic abdominal aortic aneurysm

SARAH: Yes, during the first 5 years following surgery, endovascular repair actually had better survival rates than open surgery. After that, and up to 9 years of follow up, the survival advantage of endovascular repair was not maintained.

PETER: Still, compared to previous trials, the survival benefits lasted much longer before they evened out…

BOB-Lederle-1: “Our study is newer, and I think the endovascular repair and techniques and materials are somewhat improved and… In any case, it took a lot longer time for that to happen but it still happened.”

SARAH: That was the lead investigator of the NEJM study, Frank Lederle, from the Department for Veterans Affairs Medical Center, in Minneapolis.The team found that rates of rupture were higher among patients who underwent open surgery: 6 ruptures occurred among the 444 who underwent endovascular repair, vs. none in the open surgery group. The events were rare and were not linked to mortality, said Lederle, who concluded:

Bob-Lederle-2: “I think that it’s reasonable to go with the patient’s preference because really after several years it’s the same so there are certain advantages to the open repair: you don’t have to come back for imaging and some people don’t want to come back. And some people have another concern, like they don’t want to be disabled for the first two months after the procedure –they might prefer endovascular. But I think it’s a strong argument for getting the patient involved and working out a solution that’s an individual solution.”

SARAH: Frank Lederle, from Minneapolis.


VIRGULE MUSICALE
 
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PETER: Apparently, US patients with online access to their medical records are using MORE traditional health care services than those who aren’t using online services

SARAH: Yes they had more office visits, emergency room visits, hospitalization rates, etc. These findings come as a surprise: the authors expected that being able to request prescription refills, schedule appointments -- all this online --would decrease in-person services. But they found a mean increase of 0.7 clinic visit per member per year.

Bob-Palen: “It’s not enormous but over a couple hundred thousand patients, it can make some demands on resources that you’d have to account for”

SARAH: This was Dr. Ted Palen, from Denver, CO, whose team compared the rate of in-person services among users and non-users of online access systems. Both groups contained about 44,000 matched users and non-users. They also compared users before and after they signed up for online access. The results are detailed in JAMA.

PETER: So what do we take from this?

Bob-Palen: “We need to learn how to best manage the use of these online tools so that in the long run we can deliver the best care to patients. It could be that people who are engaged in the system more right after they sign up for online access may use more services initially and they actually have a better health status and in the long run they’ll need less services, but we don’t know that yet.”

SARAH: Dr. Palen, from Denver, CO, who said his team will be investigating several hypotheses that could explain this unexpected association.


VIRGULE MUSICALE

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PETER: Children with parents suffering from chronic pain are more prone to chronic pain too…

SARAH: Yes, while having one parent reporting chronic pain increased adolescents’ risk of also experiencing it, the odds increased even more when both parents reported chronic pain. This is according to a large study looking at how different family environments influence chronic pain in children. Family structure also had an influence: children living in single-parent households, whose mother reported chronic pain, were also at increased risk for chronic pain compared to kids in 2-parent households.

Bob-Palermo: “Maybe in the households were only mothers are present there’s more family stress, there may be more burden or strains on the parents and family functioning might be poorer over all… So I hope this encourages researchers to really focus on understanding the family environment –to know for example whether when parents have chronic pain if there are specific assessment and treatment strategies that could be implemented with the children, both to prevent the development of chronic pain and also to treat pain that might be there in the children already. That’s exactly what we need to move towards, is how to incorporate treatments for the family if the patient emerges in an adult clinic or if the patient emerges in the pediatric clinic as a child patient.”

SARAH: This was Tonya Palermo, from the University of Washington in Seattle, who wrote an editorial about the study in Archives of Pediatric Adolescent Medicine.


BREVE 1 Sur fond musical
Maternal smoking during pregnancy was associated with wheeze and asthma in preschool children, even among those who were not exposed to maternal smoking after birth, according to a study published in Archives of Pediatrics & Adolescent Medicine. The authors wrote that the risk followed a dose-response pattern in relation to maternal cigarette consumption during the first trimester of pregancy.

And …..
 
BREVE 2
New data provide support for the safety and efficacy of parathyroid hormone therapy in hypoparathyroidism for up to 4 years. The findings, published in The Journal of Clinical Endocrinology and Metabolism, showed so-called PTH 1-84 maintained serum calcium concentrations, while significantly reducing supplemental calcium and vit. D requirements. Bone mineral density increased inside the lumbar spine solely.

That's all from MDFM for now. We'll be back next week
 
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