[Jan 2024]. This is a summary of the email I sent to the Advisory Council on Alzheimer's Research, Care, and Services. The Advisory Council advises the Secretary of the US Department of Health and Human Services on Alzheimer's affairs. The Council meets quarterly and takes comments from the public and organisations related to Alzheimer's. I received a reply back that my email would be included in the package distributed in the council members during their January 22 meeting:

[Summary of my email]

My name is Larry Blancett and I retired from the Department of Veterans Affairs Atlanta Regional Office in 2009, where I worked in the accounting and finance section. I have been living in Ghana for the past 14 years.

There is an urgent need to investigate the results of the Emory University montelukast Alzheimer's clinical trial.

Emory montelukast Alzheimer trial
https://clinicaltrials.gov/ct2/show/NCT03991988

The preliminary results on the Emory trial for montelukast were posted in December 2023 in clinicaltrials.gov. The results were historic in that it marked the first time in FDA clinical trial history that early Alzheimer's and mild cognitive impairment (MCI) participants showed cognitive improvement over a year's time. However there was a problem with the results. The placebo group improved in the cognitive tests, and the montelukast treated group declined. The placebo group also improved in CSF amyloid and tau measurements.

From the results, it is evident that the montelukast and placebo medications were switched between the groups. It appears that the placebo group was given the montelukast medication, and montelukast group was given the placebo pills. It appears to me to be deliberate.

It is important to investigate the switching of medications and find out who was responsible. The FDA should also investigate which medication individual trial participants actually received. That way, the correct results could be reconstructed.

The NIH Toolbox Cognition Battery shows that the montelukast treated group went from 35.4 to 33.0, which indicates a decline. The placebo group went from 35.4 to 37.3 and showed improvement, not something you would expect to see. Further cerebrospinal fluid (CSF) amyloid and tau measurements showed reductions in the placebo group, which are positive indicators and also not expected. There were no serious adverse events in either group.

I suggest that Dr Ihab Hajjar, principal investigator of the Emory montelukast trial, should be contacted. He may know which participants actually got the montelukast medication. He left Emory soon after the trial ended in November 2022 and took a position at the University of Texas Southwestern Medical Center, Dallas, TX. At the same time, Biogen was negotiating buying Reata Pharmaceuticals in Plano, TX, a suburb of Dallas. They completed the deal for $7.3 billion in July 2023. Much of Reata's research was done at UT Southwestern labs. The university that Dr Hajjar went to has now got strong Biogen connections.

Dr Hajjar's info page
https://utswmed.org/doctors/ihab-hajjar/

Dr Spencer Rozin is another person that should be contacted. In 2017 he published a study using montelukast to treat dementia patients. This study was taken from case studies he made as a part of an patent application submitted by Jack William Schultz filed years earlier for a montelukast controlled release medication to treat Alzheimer's and other dementias. Mr Shultz was granted a patent in 2015. Mr Shultz is now in his 80's and appears to have ceded much of the control over the patent to Dr Rozin.

Dr Rozin appears to be the driving force in starting the Emory montelukast in 2019. The trial started with 150 participants but was halted during the COVID-19 pandemic. It started back again in 2021 but was reduced to 32 participants. It was completed in November 2022 and the results were not submitted until November 2023.

Any person or company that would want to tamper with this clinical trial would have to deal with Dr Rozin. Dr Rozin's patent depends on getting good results on the Emory trial so that he can get backing for his own FDA clinical trial for his controlled release version. A drug maker would have to get Dr Rozin's cooperation to interfere with the Emory trial, which would delay Dr Rozin's own clinical trial for a couple of years. A drug maker would have to compensate Dr Robin for those extra couple of years it needs without montelukast competition to establish its own monoclonal antibody treatment for Alzheimer's. If it had to compete with the generic montelukast, which could be more effective, they could lose billions of dollars.

After the completion of the Emory trial, Dr Rozin decided to retire from his own successful private practice at the end of 2023.

https://patents.justia.com/inventor/jack-william-schultz

Dr Rozin's clinical study
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5420184/

Many physicians were waiting for the results of the Emory trial. Montelukast is an anti-inflammatory medication FDA approved for asthma, and some doctors are willing to prescribe it off label in higher dosages for Alzheimers if the trial results were positive. Now they are still waiting. Sincerely, Larry Blancett

[Jan 2024]. The first phase 3 clinical trial for Chronic Obstructive Pulmonary Disease (COPD) using montelukast as a treatment was conducted at the Kaiser Permanente HMO in Portland, Oregon from 1999 to 2002. Evidently it was not a great success because no results were reported to clinicaltrials.gov after its completion.

Since then there have been many clinical trials and studies using montelukast to treat COPD and the results have only shown slight or no effectiveness. This is despite research showing that leukotrienes are envolved in COPD inflamation.

The problem with these trials and studies is that all were using 10 mg once a day, which was the FDA approved dosage for asthma treatment. Once a day dosage is not the most effective treatment for any medical condition because montelukast has a half life of only about 4 hours. Within 24 hours, it has almost been completely eliminated from the body.

Merck chose the very small theraputic dose for asthma of 10 mg once a day for adults and 5 mg once a day for children for FDA approval for asthma. The reason they chose this small once a day dosage over more effective multiple daily doses is that children with asthma were a large part of their market, and they discovered that many children were having neurological side effects. Merck made it once a day thinking it would reduce the side effects. Once a day dosage has proved to be only mildly effective in treating asthma and not effective in treating many other medical conditions in many clinical trials. Unfortunately the sponsors of most of the montelukast clinical trials have made the same mistake of dosing at 10 mg once a day which have resulted in the trials failing.

[Feb 2024]  Evidence exits that montelukast reduces neuro-inflammation and helps prevent the brain's immune cells from eliminating neuro-synapses. However this preserving of synapses may be a problem for children taking montelukast for asthma. As children adapt to their environment, their brains go through synaptic pruning, which is the process by which some synapses that are not being used are eliminated by the brain's immune system. My unproven theory is that montelukast interferes with synaptic pruning, and this could be the reason that children have more neurological side effects. Whatever the reason, it is possible to modify montelukast so that it could not pass through the blood brain barrier (BBB), which would reduce the neurological side effects children have while still maintaining its asthma treatment properties. I ran across some evidence that montelukast could be modified so that it does not cross the BBB.

In my search, I have found an example of the opiate receptor blocking drug Naloxol, which was modified so that it can not cross the BBB. Naloxol is a derivative of the opiate rescue drug Naloxone. Naloxol blocks opiate receptors and therefore counters the affects of opiates. 

Opiates are commonly prescribed for severe pain. However a common side effect is opiate induced constipation. To solve this problem, AstraZeneca modified naloxol to create naloxegol, which can not cross the BBB. When the patient takes opiate pain medication, he or she also takes naloxegol, which can not cross the BBB and therefore can not interfere with the pain relief provided by the opiate. Naloxegol blocks opiate receptors in the gastrointestinal tract and therefore prevents opiate induced constipation.

Naloxegol is the result of modifying naloxol using the process of pegylation, which is the attachment or amalgamation of polyethylene glycol polymer chains to targeted molecules. The newly created naloxegol has a much greater molecular mass than naloxol, is larger in spacial size and has more hydrogen bonds. Naloxol has a molecular mass of 329 whereas naloxegol is 651. Thus naloxegol is too large to pass through the BBB but can still block opiate receptors in the gastrointestinal tract.

Montelukast has a molecular mass of 586 and using pegylation, its mass and size could be increased enough to prevent it from passing through the BBB. Just as naloxegol is effective, I believe the new modified montelukast could be designed to retain its effectiveness at inhibiting leukotrienes. Lab tests and clinical trials would have to be done verify it.

The biggest problem is getting a drug maker to do the work to create this product. Drug companies will do the work only if they can see future profits. I think there can be hugh profits to be made if a new child safe version of montelukast were marketed. Montelukast is a highly popular treatment for childhood asthma around the world despite the black box warnings, and a safer substitute would be well received, fetch a higher price and produce high profits. Further instead of once a day, it could be taken two or more times a day, making it much more effective for childhood asthma.

Another option is that the reseach for a new children's version of montelukast could be sponsored by the US government or by another country.

https://en.wikipedia.org/wiki/PEGylation

https://en.m.wikipedia.org/wiki/Naloxegol

https://www.healthline.com/health/synaptic-pruning

[Feb 2024]  I recently ran across a clinical trial in clinicaltrials.gov using montelukast as a treatment for long covid. Patients with long covid exhibit increased chronic inflammation, and montelukast's ability to inhibit leukotrienes and reduce chronic inflammation make it a good candidate as a treatment. 

The problem is that once again, participants are being given only one 10 mg tablet once a day, which is the approved dosage for asthma. Since montelukast has a half life of only about 4 hours, the drug will lose its effectiveness about halfway through the 24 hours period. A effective treatment would require at least twice a day dosing at a minimum. Montelukast at once a day may be minimally effective for asthma but is likely not effective for other medical conditions.

Researchers need to stop assuming that 10 mg once a day is the most effective dosage. If required, they need to go get approval from their supervising authorities for dosing two or three times a day and at higher dosages. Otherwise their clinical trials will fail. This failure to use an effective dosage also wastes a lot of research time and money. It also discourages other researchers from using montelukast for other trials.

In this particular trial, the estimated completion date was 31 Aug 2023. No results have been posted as of this writing.

https://clinicaltrials.gov/study/NCT04695704

[April 2024] I emailed the FDA Office of Scientific Investigations in January about the results of the Emory trial. They replied in February that they are considering an investigation into the Emory trial but can't give out any information and that I would have to inquire through the Freedom of Information Act. I am sure any reply I get that way will take a long time and be heavily redacted. The investigation may uncover the breaking of federal laws so the FBI could also get envolved.

The Intelgenx Technologies montelukast Alzheimer's clinical trial is scheduled to be completed by May 30 of this year in Canada. Because of the Emory fiasco, the Intelgenx version of montelukast may prove to be the first Alzheimer's drug to show cognitive improvement.