{"id":28952,"date":"2012-10-14T19:49:42","date_gmt":"2012-10-14T23:49:42","guid":{"rendered":"http:\/\/1boringoldman.com\/?p=28952"},"modified":"2012-10-14T19:50:12","modified_gmt":"2012-10-14T23:50:12","slug":"already","status":"publish","type":"post","link":"https:\/\/1boringoldman.com\/index.php\/2012\/10\/14\/already\/","title":{"rendered":"already?…"},"content":{"rendered":"
\n
\n
Lilly, Roche drugs chosen for Alzheimer’s prevention trial<\/font><\/strong><\/u><\/a>
Press Release: Eli Lilly & Co<\/font><\/strong>
12 Oct 12<\/div>\n

<\/p>\n

Eli Lilly & Co.’s solanezumab and Roche Holding AG’s gantenerumab were selected for a long-term Alzheimer’s trial run by Washington University at St. Louis scientists seeking to block the disease’s symptoms. The experimental medicines will be tested in a trial called DIAN TU involving 160 people with a mutation that guarantees they will develop Alzheimer’s at an early age, perhaps as young as 30, the university said in a statement Wednesday. If the trial is successful, it may lead to those drugs being widely used for people who may have a family history of the disease. Solanezumab slowed the decline in some patients with mild Alzheimer’s and provided no benefit to more advanced patients, Indianapolis-based Lilly announced in August. On Oct. 8, an independent group of scientists confirmed the findings.<\/p>\n

“Trying to prevent Alzheimer’s symptoms from ever occurring is a new strategy,” said John C. Morris, the trial’s principal investigator, in Wednesday’s statement. That will be the goal of the research, he said. Lilly and Roche, based in Basel, Switzerland, have agreed to make their treatments available for the study at no cost, and will support the trial with grants. Another $4.2 million has been given to the investigation from the Alzheimer’s Association, an advocacy group based in Chicago. The trial will be conducted by Washington University’s unit of the Dominantly Inherited Alzheimer’s Network, or DIAN, an international group of scientists studying rare genetic mutations that cause the disease. The information gathered in these patients may enable better treatment for all dementia patients.<\/p>\n

Roche’s gantenerumab binds to clumps of beta amyloid, a protein thought to cause the disease. The drug is thought to help remove the clumps from the brain, and is in a mid- to late-stage company trial that started in 2010. Lilly’s solanezumab removes the beta amyloid before it forms plaques. Another Lilly drug, called a beta secretase inhibitor, is in testing by the company and may be included in the university research as well, according to Wednesday’s statement. That drug is thought to work by reducing the amount of beta amyloid produced in the brain. The trial, which may start early next year, will test the medicines in inherited early-onset Alzheimer’s patients. The researchers will see if the treatments can prevent the loss of brain function.<\/sup><\/div>\n<\/blockquote>\n

Wow – that was quick! No wonder that solanezumab went from a bust<\/em> to a maybe<\/em> last week [SHOW ME THE DATA!…<\/font><\/u><\/a><\/strong>, d\u00e9jà vu…<\/font><\/u><\/a><\/strong>]. DIAN<\/font><\/strong><\/u><\/a> [Dominantly Inherited Alzheimer’s Network] is new to me, but looks to be pretty solid:<\/div>\n
\n
Clinical and biomarker changes in dominantly inherited Alzheimer disease<\/font><\/strong><\/u><\/a>
by Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM, Holtzman DM, Santacruz A, Buckles V, Oliver A, Moulder K, Aisen PS, Ghetti B, Klunk WE, McDade E, Martins RN, Masters CL, Mayeux R, Ringman JM, Rossor MN, Schofield PR, Sperling RA, Salloway S, Morris JC; and the Dominantly Inherited Alzheimer Network.<\/sup>
New England Journal of Medicine<\/font><\/strong>. 2012 367[9]:795-804.<\/div>\n

<\/p>\n

BACKGROUND<\/font><\/strong><\/u>: The order and magnitude of pathologic processes in Alzheimer’s disease are not well understood, partly because the disease develops over many years. Autosomal dominant Alzheimer’s disease has a predictable age at onset and provides an opportunity to determine the sequence and magnitude of pathologic changes that culminate in symptomatic disease. METHODS: In this prospective, longitudinal study, we analyzed data from 128 participants who underwent baseline clinical and cognitive assessments, brain imaging, and cerebrospinal fluid (CSF) and blood tests. We used the participant’s age at baseline assessment and the parent’s age at the onset of symptoms of Alzheimer<\/span>‘s disease<\/span> to calculate the estimated years from expected symptom onset (age of the participant minus parent’s age at symptom onset). We conducted cross-sectional analyses of baseline data in relation to estimated years from expected symptom onset in order to determine the relative order and magnitude of pathophysiological changes.
RESULTS<\/font><\/strong><\/u>: Concentrations of amyloid-beta (Aβ)(42) in the CSF appeared to decline 25 years before expected symptom onset. Aβ deposition, as measured by positron-emission tomography with the use of Pittsburgh compound B, was detected 15 years before expected symptom onset. Increased concentrations of tau protein in the CSF and an increase in brain atrophy were detected 15 years before expected symptom onset. Cerebral hypometabolism and impaired episodic memory were observed 10 years before expected symptom onset. Global cognitive impairment, as measured by the Mini-Mental State Examination and the Clinical Dementia Rating scale, was detected 5 years before expected symptom onset, and patients met diagnostic criteria for dementia at an average of 3 years after expected symptom onset.
CONCLUSIONS<\/font><\/strong><\/u>: We found that autosomal dominant Alzheimer’s disease was associated with a series of pathophysiological changes over decades in CSF biochemical markers of Alzheimer’s disease, brain amyloid deposition, and brain metabolism as well as progressive cognitive impairment. Our results require confirmation with the use of longitudinal data and may not apply to patients with sporadic Alzheimer’s disease.<\/sup><\/div>\n
 <\/div>\n<\/blockquote>\n
Here they have an inherited disease with a somewhat predictable course and a biomedical treatment strategy – antibodies directed at the beta-amyloid thought to be causative in the condition. The problem is that one of the drugs has not made it through a Phase 3 Clinical Trial [gantenerumab<\/font><\/strong>] and one that has, for all intents and purposes, just flunked two Phase 3 Clinical Trials [solanezumab<\/font><\/strong>] unless you pool the trials and only consider a subset of subjects<\/em>. There is an instructive write-up about the solanezumab <\/font><\/strong>trials entitled The Solanezumab Benefit: Oh, So Small, But Probably Real<\/font><\/u><\/strong><\/a> on the Alzheimer’s research site.<\/div>\n

<\/p>\n

Are they going off half-cocked? Probably. On the other hand, reading the articles the excitement is palpable. They really seem to be on the track of something, and at least in dominantly inherited Alzheimer disease they have a biomarker, a known course, something of a pathophysiology, and a fledgling treatment strategy with some positive short-term results. It will be interesting to see if they proceed with a careful scientific progression or if they’ll act like a run-away train and put marketability before good sense… <\/div>\n","protected":false},"excerpt":{"rendered":"

Lilly, Roche drugs chosen for Alzheimer’s prevention trial Press Release: Eli Lilly & Co 12 Oct 12 Eli Lilly & Co.’s solanezumab and Roche Holding AG’s gantenerumab were selected for a long-term Alzheimer’s trial run by Washington University at St. Louis scientists seeking to block the disease’s symptoms. The experimental medicines will be tested in […]<\/p>\n","protected":false},"author":2,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_bbp_topic_count":0,"_bbp_reply_count":0,"_bbp_total_topic_count":0,"_bbp_total_reply_count":0,"_bbp_voice_count":0,"_bbp_anonymous_reply_count":0,"_bbp_forum_subforum_count":0,"footnotes":""},"categories":[2],"tags":[],"class_list":["post-28952","post","type-post","status-publish","format-standard","hentry","category-politics"],"_links":{"self":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/28952","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/comments?post=28952"}],"version-history":[{"count":6,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/28952\/revisions"}],"predecessor-version":[{"id":28958,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/posts\/28952\/revisions\/28958"}],"wp:attachment":[{"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/media?parent=28952"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/categories?post=28952"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/1boringoldman.com\/index.php\/wp-json\/wp\/v2\/tags?post=28952"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}