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continued from previous reply) From these two research projects, there is evidence that cysteinyl leukotriene blockers, such as montelukast, could prevent chronic microglia activation in earlier stages of AD and dementia and thus prevent the break up of microglia in the later stages.
There is plenty of evidence that montelukast would be effective. But it is only if Intelgenx Pharmaceuticals or some other company or organization can pay for a clinical trial that we can know for sure.
Note: Ludwig Aigner is no longer listed as the lead person in his 2015 research. His name has now dropped to the bottom on the research credits. Possibly, the reason could be a dispute with Paracelsus University over Dr Aigner's pending patents for montelukast as treatments for Alzheimer's, dementia and Parkinson's. He now works for Intelgenx Pharmaceuticals.
https://en.m.wikipedia.org/wiki/Microglia
Medscape article requires making up password and logging in. It's quick and free.
http://www.medscape.com/viewarticle/705409
http://www.nature.com/articles/ncomms9466
Thanks Lane for this great find on microglia. I found the 2009 Medscape article about Dr Streit's research very informing, and based on the research by Dr Streit and also by Dr Ludwig Aigner and their teams, I can see the importance of microglia in the the progression of Alzheimer's and other dementias.
According to Wikipedia, microglia are resident macrophage cells, acting as the first and main form of active immune defense in the central nervous system (CNS). Microglia are widely distributed in the CNS and make up 10 to 15% of all cells found in the brain. Microglia are key cells in overall brain maintenance - constantly scavenging the CNS for plaques, damaged or unnecessary neurons and synapses, and infectious agents. Damage to the microglia would result in serious injury to the brain.
In Dr Streit's 2009 research on microglia, he and his colleagues obtained 19 specimens from the brain bank at the Institute for Clinical Neuroanatomy at the University of Frankfurt, Germany. The specimens represented a range of pathologies from no AD to severe AD.
The hypothesis at the time was that amyloid deposits in the brain trigger an inflammatory reaction. According to this theory, the inflammatory response activates microglial cells to produce toxic substances that in turn cause neurons to degenerate. But when he looked in the areas next to destroyed neurons in the AD specimens, he couldn't find any activated microglial cells. What he found was microglial cells that had broken apart, fragmenting into many small pieces. Therefore he concluded that AD is linked to microglia degeneration. He didn't adequately explain the reason for the degeneration. He also stated that because that he could not find activated microglia, inflammation is not a major factor. I think he was wrong on that interpretation. The microglia could have become activated at an earlier stage, causing inflammation, and then become exhausted and fragmented at a later stage of AD.
He also stated that many studies had failed to show that anti-inflammatory drugs could have a positive affect in the treatment of AD. I believe he was referring to studies of Non-steroidal anti-inflammatory drugs (NSAIDs) during that time period. Numerous studies showed then that they did not work. However there are other classes of anti-inflammatory drugs that were not studied as AD treatments at the time of his research.
Moving on to Dr Ludwig Aigner's research in 2015, he and his team examined the brains of young and old rats treated with montelukast. One group of young rats was untreated. Another group had montelukast added to its food for 6 weeks. One group of old rats was untreated. Another group of old rats also had montelukast added to their food for 6 weeks. Montelukast (Singulair) is a generic drug approved for the treatment of asthma. Within the brain, the drug blocks cysteinyl leukotrienes, inflammatory substances secreted by microglia, from entering nearby brain cells.
The brains of the young rats not treated showed no signs of inflammation or microglia activation. The brains of the old rats not treated showed signs of inflammation, and in particular, microglia activation with soma enlargement (the soma is the bulbous part of the cell containing the nucleus). The brains of the old rats treated with montelukast had microglia with normal size soma and reduced inflammation.
My theory is that microglia can become activated causing chronic inflammation in the earlier stages of dementia and over the years the microglia can become exhausted and break up, leaving the brain unable to keep up with maintenance and defend itself from outside agents. Montelukast appeared to reverse the activation.
So why in Dr Aigner's research did the activated microglia in the old rats not break up. My theory on this is that rats have a short life span compared to humans. Therefore they will never live long enough for the microglia to break up after chronic activation.
(continued in next reply)
A different view of inflammation in Alzheimer's disease
Lane Simonian
Posted: Sunday, March 5, 2017 10:31 PM
Joined: 12/12/2011
Posts: 4066
Microglia (the brain's main immune cells) are likely over-activated during the early stages of Alzheimer's disease leading to inflammation but damaged as the disease progresses:
New research suggests that Alzheimer’s disease (AD) could be caused by the degeneration of microglia, the cells in the central nervous system that normally protect neurons...
This new hypothesis challenges the theory that AD is the result of amyloid protein deposits in the brain that trigger an inflammatory reaction. According to this theory, the inflammatory response activates microglial cells to produce toxic substances that in turn cause neurons to degenerate. This inflammation theory has been implicated not only in AD but in other neurological diseases, including Parkinson's disease, amyotrophic lateral sclerosis (ALS), and Huntington's disease.
"If people are claiming that these activated microglia kill neurons by producing toxins of various kinds, then I should expect to see these activated microglia right next to the dying neurons," said lead author and microglia expert Wolfgang J. Streit, PhD, from the department of neuroscience at the McKnight Brain Institute at the University of Florida College of Medicine, in Gainesville.
"But when I looked in those regions, I couldn't find a single activated microglial cell," he told Medscape Neurology. "What I found instead were microglial cells that were breaking apart, fragmenting into many little pieces."
These observations might help explain why anti-inflammatory drugs do not seem to prevent or diminish dementia, he suggests. And if borne out, they could result in a reevaluation of current treatment approaches for AD.
Inflammation may play a role in Alzheimer's disease (activated microglia, for instance, add to oxidative stress), but its role may decline as the disease continues. Furthermore, the damage done to microglia by oxidative stress may prevent them from removing toxins from the brain.
We are sitting on a gold mine here with montelukast
THE ANTI-ASTHMATIC DRUG MONTELUKAST ALTERS MICROGLIA PHENOTYPE AND SYNUCLEOPATHY, AND RESTORES LEARNING AND MEMORY IN AN ANIMAL MODEL OF LEWY BODY DEMENTIA
Julia MarschallingerEmail the author Julia Marschallinger, Barbara Altendorfer, Nadine Pillichshammer, Garnweidner-Raith Julia, Edward Rockenstein, Eliezer Masliah, Ludwig Aigner
PlumX Metrics
DOI: http://dx.doi.org/10.1016/j.jalz.2017.06.233
Article Info click to expand contents
Background
Neurodegenerative diseases are associated with increased neuroinflammation. Leukotrienes are small lipid mediators of neuroinflammatory processes, and thus, leukotriene signaling might be a therapeutic target for neurodegenerative disease such as AD, PD, or Lewy body dementia (LBD).
Methods
6-month old PDGF-promoter-alpha-synuclein (PDGF-a-syn) D-line transgenic mice (abbreviated D-line), an animal model for LBD, were treated per oral gavage daily over a period of 42 days with montelukast (10 mg/kg), an approved leukotriene receptor antagonist for the treatment of asthma. Behavioral analyses (Morris Water Maze – learning and memory) of the animals were performed between days 28 and 40. After transcardial perfusion of the mice on day 42, histological analyses of the hippocampus (proliferation, cell survival, neuroinflammation, alpha-synuclein load) were assessed.
Results
We observed elevated levels of 5-LOX protein, the rate limiting enzyme in leukotriene production, in the hippocampus of 6 months old PDGF-promoter-alpha-synuclein (PDGF-a-syn) mice, an animal model for LBD. D-line animals exhibited elevated levels of neuroinflammation, and most importantly, had learning and memory deficits. Treatment of 6 months old D-line mice for 6 weeks with the leukotriene receptor antagonist Montelukast fully restored learning and memory to a level comparable to WT animals without having any adverse effects regardless of the phenotype. Montelukast significantly reduced microglia soma size (a typical morphological surrogate for microglia activation) and reduced the particle size of the phagosomal marker CD68 suggesting either a reduced microglial activity or a restoration of the phagocytic / lysosomal activity, which is otherwise disturbed in microglia of the aged and of the neurodegenerative brain. Moreover, the Montelukast treatment altered the synucleopathy in the D-line mice.
Conclusions
In summary, the leukotriene receptor antagonist Montelukast was highly efficient in restoring cognitive function in an animal model of LBD, most likely but not necessarily limited through its anti-inflammatory action on microglia. This work paves the road for a further development of Montelukast for the treatment neurodegenerative diseases.
And a sugar daddy for montelukast
Montelukast (Singulair) as preventive for Alzheimers igxt
Google Spencer I Rozin montelukast igxt
Excellent news. Google Spencer I Rozin and montelukast. Very exciting.
I'm hoping they deliver but I'm not holding my breath
Health Canada commits to a 30-day default, review period for authorization. That is, if Health Canada does not issue a Non Satisfactory Notice, during the review period, the trial may proceed on the basis of default authorization. Health Canada has an administrative 7-day review target for comparative bioavailability trials, and some Phase I trials in healthy humans volunteers. So latest next week for montelukast trial.
Spencer I Rozin. Anyone interested in the success montelukast will bring this company Google this man's case study of montelukast on people. If you don't invest after that well I can't do more.
Montelukast will be a big driver coming up
BB things seem to be moving well. Montelukast interim results mid year. Nda filing for Ed before year end. Very good news. And hopefully start of rizaport production mid year, Europe and United States.
Igxt.
SAINT-LAURENT, QUEBEC--(Marketwired - Nov. 9, 2017) - IntelGenx Corp. (TSX VENTURE:IGX)(OTCQX:IGXT) (the "Company" or "IntelGenx"), today announced that it has submitted a clinical trial application ("CTA") to Health Canada for approval to initiate its Phase 2a proof of concept ("POC") study with Montelukast in mild to moderate Alzheimer's Disease ("AD").
SAINT-LAURENT, QUEBEC--(Marketwired - Nov. 9, 2017) - IntelGenx Corp. (TSX VENTURE:IGX)(OTCQX:IGXT) (the "Company" or "IntelGenx"), today announced that it has submitted a clinical trial application ("CTA") to Health Canada for approval to initiate its Phase 2a proof of concept ("POC") study with Montelukast in mild to moderate Alzheimer's Disease ("AD").
SAINT-LAURENT, QUEBEC--(Marketwired - Nov. 9, 2017) - IntelGenx Corp. (TSX VENTURE:IGX)(OTCQX:IGXT) (the "Company" or "IntelGenx"), today announced that it has submitted a clinical trial application ("CTA") to Health Canada for approval to initiate its Phase 2a proof of concept ("POC") study with Montelukast in mild to moderate Alzheimer's Disease ("AD").
As more starts to roll so will the price. Definitely the right direction
CONCLUSION
The use of Montelukast in patients with cognitive impairment improved memory. Its use in patients with dementia led to lessened agitation, but the effect on memory improvement may be limited by the dose selection lower than that used in the animal studies
I believe Horst and wife own about 10 million in options. I'm thinking the CFO is building up shares before the tadalafil partnership.that deal should benefit us all.
The Riddler is a fictional supervillain appearing in American comic books published by DC Comics, usually as an enemy of Batman. Created by writer Bill Finger and artist Dick Sprang, the character first appeared in Detective Comics #140. Wikipedia
Someone in the know?
Definitely an optimum delivery method.
Shortest shorty short
The last sentence using montelukast as a prophylactic to prevent dementia is big. If that happens it will be big.
Cognitive decline and dementia are a growing problem as the population ages. Effective therapies to prevent and treat these problems are limited. Neuro-inflammation has been suggested as a cause of dementia [1]. Montelukast is a leukotriene receptor antagonist used to treat seasonal allergies and asthma. It acts as a cysteinyl leukotriene (CysLT1) receptor antagonist blocking the action of leukotrienes and decreasing inflammation [2]. Animal studies have shown that administering Montelukast improves memory function [3]. This case series of patients in a private Internal Medicine practice between 2013-2014 used Montelukast in patients with various levels of memory impairment and dementia. Patients were given Montelukast 80 mg daily in 4 divided doses every 2-3 hours. Memory impaired patients had subjective improvement in the memory and recall. Patients with dementia were noted by family members to be less agitated, but had no memory improvement at the doses used. Montelukast may be useful to treat memory impairment and dementia. Long term use might act as a prophylactic to prevent dementia.
On April 13, 2017, RedHill, together with IntelGenx Corp. (IGX.V) (IGXT) ("IntelGenx"), announced that the Ministry of Health of Luxembourg had granted national marketing authorization for RIZAPORT® (5 mg and 10 mg). The national marketing authorization was granted in Luxembourg on the basis of the European Decentralized Procedure (DCP), in which Luxembourg served as the Concerned Member State. The approval in Luxembourg marks the completion of the current marketing approval process for RIZAPORT® under the European DCP.
Advantages Edit
The design of thin film as an oral drug delivery technology offers several advantages over other modes of drug delivery, such as ingestible tablets, chewable tablets, orally dissolving tablets, softgels, liquids or inhalants:[8]
The sublingual and buccal delivery of a drug via thin dissolvable film has the potential to improve the onset of action, lower the dosing, and enhance the efficacy and safety profile of the medicament.
All tablet dosage forms, softgels and liquid formulations primarily enter the blood stream via the gastrointestinal tract, which subjects the drug to degradation from stomach acid, bile, digestive enzymes and other first-pass effects. As a result, such formulations often require higher doses and generally have a delayed onset of action.
Conversely, buccal and sublingual thin-film drug delivery can avoid these issues and yield quicker onsets of action at lower doses.
Thin film is more stable, durable and quicker dissolving than other conventional dosage forms.
Thin film enables improved dosing accuracy relative to liquid formulations since every strip is manufactured to contain a precise amount of the drug.
Thin film not only ensures more accurate administration of drugs but also can improve compliance due to the intuitive nature of the dosage form and its inherent ease of administration. These properties are especially beneficial for pediatric, geriatric and neurodegenerative disease patients where proper and complete dosing can be difficult.
Thin film's ability to dissolve rapidly without the need for water provides an alternative to patients with swallowing disorders and to patients suffering from nausea, such as those patients receiving chemotherapy.
Thin film drug delivery has the potential to allow the development of sensitive drug targets that may otherwise not be possible in tablet or liquid formulations.
From a commercial perspective thin film drug delivery technology offers an opportunity to extend revenue lifecycles for pharmaceutical companies whose drug patent is expiring and will soon be vulnerable to generic competition.
Pharmaceutical drugs can be contained within an abuse-deterrent film matrix that cannot be crushed or injected by patients, and rapidly absorbs under the tongue to ensure compliance.
Facilitates absorption 3 to 10 times greater than an oral tablet---only surpassed by hypodermic injection.
Stealth accumulation with all they have coming
Very informative response. Thank you so much
Don't worry. Up and down but slowly creeping into the big leagues.
Chemo buys a subsidiary of Juste and promotes integration in the pharmaceutical sector
The group of Hugo Sigman acquires a division of the Madrid company
ALFONSO SIMÓN RUIZ 03-03-2017 08:07
To printChemo buys a subsidiary of Juste and promotes integration in the pharmaceutical sector
Headquarters of Grupo Chemo in Madrid. ()
The chemical and pharmaceutical group Chemo , through its subsidiary Exeltis , has purchased from Madrid's Juste laboratory its Juste Farma division , which sells gynecological products, central nervous system and primary care. In this way, the integration movements in the sector are encouraged.
This is one of the few operations between Spanish laboratories in recent times, ahead of what experts in the sector point out for the coming months: the corporate movements in which national pharmaceutical companies can participate. The operation was carried out by the Chemo Group, which has acquired the subsidiary Juste Farma, from the Madrid laboratory Juste.
Chemo incorporates the pharmaceutical products of gynecology, central nervous system and primary care to its asset portfolio, as well as absorb the sales network of this division of Juste, a company that has been advised in the transaction by Deloitte . Industry sources indicate that the integration of the two companies' templates has just taken place. The amount of the transaction has not been exceeded.
These therapies acquired by Chemo reinforce the presence of Exeltis in Spain thanks to the sum of the research, promotion and marketing activities of these medicines. It also incorporates drugs for the treatment of insomnia, depression or epilepsy
The operation is part of an international situation of concentration in the sector, due to the need of laboratories to market new products.
The Juste laboratory was created in Madrid in 1922 by Rafael Juste, focusing on his beginnings in products for ophthalmology. Out of the transaction is Justesa Imagen, the large chemical division , which manufactures active ingredients (the raw material for drugs) destined for laboratories around the world. During these years, the company has been heavily specialized in the production of radiological contrast media, which served to initiate internationalization since the 1970s. With production plant in Coslada, in 2015 it invoiced 29.3 million euros, according to the latest data presented in the Register. It continues to be a family business, presided over by Inés Juste since 2011 as a representative of the fourth generation of the saga.
For its part, Chemo is also a family chemical pharmaceutical group created in 1977 by the Argentinean Hugo Sigman , with corporate headquarters in Spain and with three production plants in our country (in Leon, Guadalajara and Alcalá de Henares). This group - led by Leandro Sigman, son of the founder - is divided into three major international businesses. On the one hand, Chemo Industrial, with 11 industrial plants, five chemical and six pharmaceutical, for the production of ingredients of drugs and finished drugs.
Another of its subsidiaries is Mabxience , dedicated to the development of biosimilars, biological drugs that enter the market at a lower cost when the originals lose patents. These types of therapies are the most leading to diseases such as cancer, in addition to the most costly for the health system.
Finally, Exeltis, where Juste Farma is now integrated, is a brand launched in Spain in February. It adds 300 products in its portfolio in the areas of women's health, respiratory, dermatology and endocrinology, with 4,000 professionals and 35 subsidiaries. Chemo España has the holding company Kevilmare , with a turnover of 503 million in 2014, according to data collected in the Registry by Insight View.
Good info bb. Looks like Europe and Latin America may be first to bring in revenue from rizaport. Then possibly a money deal on tadalafil. Hopefully approval of rizaport in America soon. Suboxone I am not counting on. If litigation goes our way it's a bonus, a good one. Other partnerships are extra. Timing for cash flow should be ok.
IntelGenx completed construction in the first quarter last year of a state-of-the-art oral film development, manufacturing and packaging plant in Montreal. The 17,000-square-foot facility will be fully operational in the current quarter and Dr. Zerbe says work on an expansion is already underway. Article from February. Why expand ? Something is up. Conference call coming.
Please be clear.
Unusually quiet
Good things coming like you said and promotion of montelukast. Seems to be right. Cialis, rizaport. Plus any new deals.
Could someone bring down the price. Need to transfer some shares in the new year from my margin account to my tfsa