Excerpt 10 – Repeated Failures, then New Hope – 1998 – 2012
My Journey to a
Next Generation Treatment
Donald E. Moss, Ph.D.
[Setting and Summary by Jim Summerton, Ph.D.]
[ Setting and Summary: After decades of effort by Moss and his colleagues, by 1998 it appeared that Moss' wonder drug, MSF, had everything going for it to revolutionize the treatment of Alzheimer's and other conditions entailing serious memory decline, such as stroke. Demonstrated advantages of MSF included:
1. Fundamental biochemical studies, buttressed by mathematical modeling, showed just why MSF was greatly superior to the other Alzheimer's treatments that work by a similar mechanism (increase acetylcholine in the brain).
2. Studies in rats confirmed the superiority of MSF with respect to both efficacy and specificity in comparison to the other drugs available for treating memory decline in Alzheimer's. Those other drugs are plagued by poor efficacy and dose-limiting side effects (vomiting, diarrhea, cramps, nausea).
3. Studies in monkeys confirmed that the exceptional safety of MSF in rats is also seen in primates.
4. Phase 1 clinical trial results (in normal humans) further confirmed the exceptional safety of MSF.
5. Clinical trial results in Alzheimer's patients demonstrated dramatic and unprecedented improvements in memory and general quality of life for Alzheimer's patients treated with MSF.
6. A fresh new US Patent was issued in 1998 which covered the use of MSF and related sulfonyl fluorides for treating Alzheimer's and other conditions entailing serious memory decline.
7. New laboratory results in rats indicated that MSF was also effective in reversing the memory loss that often occurs in stroke.
With all these compelling advantages, what could possibly derail MSF from getting to the patients who are desperately in need of this superior treatment for memory decline ?
This EPILOGUE spells out the sad story of what could, and indeed did, go wrong, and why fourteen years after the patent was issued patients still do not have access to this wonder drug for Alzheimer's disease, stroke, and other conditions involving serious memory decline.
On a happier note, this EPILOGUE closes with an introduction to a new venture, Brain-Tools, LLC, co-founded by Moss and myself (James Summerton, Ph.D.). The objective of this new venture is to finally get MSF to patients by:
a) completing the requisite FDA-compliant clinical trials on MSF;
b) obtaining marketing approval for MSF therapeutics in the US; and,
c) producing and distributing MSF at low cost to patients.
This unconventional Brain-Tools venture is described in more detail in the subsequent POSTSCRIPT to Moss' book, and then described in still more detail on the website: www.Brain-Tools.com ]
Why is it that 99.99% of people with Alzheimer’s disease or those who are caring for a loved one with dementia have never heard of MSF? Why can an inexpensive drug that produces substantially greater improvement in quality of life than current treatments coexist and remain unused by an estimated five to six million people suffering from dementia in the U.S.? What about the other Alzheimer’s patients worldwide and the stress and grief of the estimated three caregivers that are involved with each Alzheimer’s victim?
Why isn’t MSF available to help reduce the estimated $200 billion per year that are spent in the U.S. for Alzheimer’s patient care, a cost that is estimated to escalate to a trillion dollars ($1,000,000,000,000) per year by 2050 when the Baby Boomers are in the midst of old age?
The brutal reality of the pharmaceutical industry is that it is driven by money, not by public good or benefit to society. The captains of the pharmaceutical industry meet every day in board rooms and look at whether or not to spend hundreds of millions of dollars to get a new drug through the tangled and torturous three to ten year regulatory ordeal and push it into the market. Their only concern about patients is simply whether or not there will be enough of them taking the new drug to pay back their investment and bring a few billions of dollars back to the stockholders. In my conversations with drug companies, I have never heard anyone talk about pain and suffering.
MSF is dying a slow death, strangled by patent law and regulatory obstacles, because it was born outside the wedlock between Big Pharma and Big Money.
* * *
In the spring of 1997, the rights to the still pending patent on MSF were licensed to a small biotech company in California. Their goal was to either find venture capitalists who could put up the money to push MSF through FDA approval or to sublicense the rights to a big drug company that would take it on as a new product. Either way, it seemed to be on its way.
To help raise awareness of MSF, Pati accompanied Jo Anne and me to an international conference on Alzheimer’s disease in Helsinki, Finland. A report of our clinical study in Chihuahua had been accepted for the competitive and prestigious program. The meeting was well attended and I met a woman from a large European drug company. She liked what she saw.
In the months that followed the Helsinki meeting, I followed up on my contact and sent all the information about MSF to the company for their consideration. A few more months later, I received an invitation to go to the European headquarters of the firm. They wanted to find out more about MSF and, if all went well, discuss a licensing deal. A representative from the biotech company went on the trip with me and we left as soon as travel could be arranged.
Over the two day visit, the company scientists and licensing administrators showed real interest in what MSF could accomplish. Because MSF had been introduced to them by their colleague I’d met in Helsinki, they recognized that it was fundamentally different from the drug that had been approved in 1996 (donepezil, Aricept7) as well as the second one that was expected to come on the market soon (rivastigmine, Exelon7). MSF would be a third generation AChE inhibitor that would compete with these other two, less effective drugs.
At the end of the second day, we had a grand dinner in the finest hotel in the city, one that looked over a harbor, drank wine and toasted MSF. We shook hands and slapped each other on the back. They wanted to license MSF and take it to market. The deal would be finalized when the company had verified all the information and the attorneys had reviewed the patent.
* * *
Months later, the European company notified the University that the patent was worthless. The attorney who had prepared and filed my patent had omitted important information. The patent was incomplete, absolute rubbish.
It took several readings for me to understand that the new patent that I had worked for years to obtain had turned to trash and the opportunity to license it had evaporated. As I read the letter, I felt drained and lost. I’d been transported into some cruel hell where the whole ordeal had been a vicious prank.
* * *
The remedy for the errors in the original patent application involved sending the patent back to the Patent and Trademark Office to have it reexamined. This process took more than a year. At the end of the reexamination, the patent was reissued in a valid form. But by that time the European drug company had merged with a second pharmaceutical giant. The new organization and their management team now wanted a drug to prevent Alzheimer’s disease, not just a treatment such as MSF.
The deal was dead. The biotech firm then let the MSF patent languish while they squandered their resources on another project. The University did not enforce the agreement which required that the company make progress in bringing MSF forward. In a few years, the company went bankrupt.
* * *
While we were trying to license the patent for the treatment of Alzheimer’s, another opportunity developed. Dr. Cesar Borlongan at the University of South Florida along with Dr. Isabel Sumaya and me at U.T. El Paso, tested the ability of MSF to reverse the persistent cognitive impairment after stroke in rats. Not surprising, MSF, a strong AChE inhibitor, was effective in improving the rats’ memory.
What was surprising is that we found that MSF prolonged treatment, for four weeks, increased the appearance of choline acetyltransferase, the enzyme that manufactures acetylcholine, in the brain. This work suggests that MSF has a dual action, both inhibiting the breakdown of acetylcholine as well as increasing its production. Both of these actions would increase acetylcholine and improve cognitive performance. It is also possible that the long-term increase in acetylcholine production produced by the action of MSF on this enzyme might explain its long-term enhancement in cognitive functioning seen in the Chihuahua study when the patients were switched to eight weeks of placebo.
We applied for a patent for the use of MSF for the treatment of cognitive impairments after stroke in 2002. After an eight year fight with the Patent Office, we were disappointed in 2010 when it was rejected. The failure to receive a patent was the result of technical issues, not because MSF failed to work. Further research on the effects of MSF on cognitive problems after stroke is warranted.
* * *
Meanwhile, my MSF patent for the treatment of Alzheimer’s dementia was relicensed to a second small pharmaceutical company in 2002 which used it primarily to attract investors. More years went by without any serious attempt to make progress toward getting MSF approved as a drug.
After more time, the rights were returned to the University. With no team with expertise ready to market the patent and facilitate the transfer of MSF to another drug company, more years of patent life slipped away.
In the fall of 2006, thirty-six years after doing some weekend experiments with my brother Dave, and ten years after finishing the study in Chihuahua, MSF was dying as the patent life ticked away. Disappointed with the situation, I took a leave of absence from the University. I was tired and frustrated with the absence of any effort to market the MSF patent to a drug company that might bring it to life. At 62 years old I wanted to enjoy the autumn in northern Colorado with Jo Anne at a little cabin that we had built next to the Routt National Forest.
One day in October I was surprised to get a phone call from a person who identified herself as someone hired by the University to work on licensing a patent of another faculty member, not MSF. She was a technology transfer professional who had reviewed the intellectual property portfolio and had found my MSF patent. She wanted to know more.
I drove down to El Paso within three days of the telephone call. We agreed to meet at a restaurant on the edge of campus. I described myself as a tall, old guy with graying hair pulled back in a ponytail. “You can’t miss me,” I said.
When the woman came in, she recognized me right away. I guessed that old professors look like old professors and that my description was adequate. She was a young woman with a high level of energy and she wanted to work on licensing MSF. I was delighted to have the patent pulled out and dusted off.
After two years of traveling all over the world to conferences and companies, all contacts with venture capitalists and pharmaceutical giants had been exhausted without success. The main problem was that most of patent life had been wasted. In 2008, with only seven years left, a Swiss firm took over the development of MSF.
The Swiss company immediately conducted the necessary animal tests to achieve both FDA and German regulatory approval to reintroduce MSF in a Phase One human study. The new FDA-compliant Phase One human study was carried out in Germany and was finished in August of 2010.
Like I had found in my Phase One study in the normal humans in Chihuahua, MSF was well tolerated and the study was a success. I felt proud that the German study run by teams of professionals found the same results we had obtained in Chihuahua years before. The results were announced in 2010 with only five years left on the patent.
Exhaustive new efforts to raise the additional millions of dollars required to bring MSF to market stalled. In August of 2011, with four years remaining, it was too late. Even if two hundred million dollars had been found at that time, approval would take three more years, leaving only one year to recover the investment. It couldn’t be done.
A little bit of me seems to die each day as the patent clock runs down to zero and this story of triumph and tears comes to an end. The triumph was the study in Chihuahua where the patients showed dramatic improvement. The tears are for the millions of others who are suffering with dementia without getting the benefit of the best available treatment.
* * *
My MSF patent will expire in August, 2015. It will be pronounced dead by conventional standards based on whether or not a pharmaceutical company can make billions of dollars. But MSF is not dead. Its ability to rekindle the mind and push back the darkness of dementia is unchanged by dates on patent documents or balance sheets in corporate offices. Regardless of ink on paper, MSF is still a drug that can change peoples’ lives. Nothing can take that away.
Dementia patients throughout the world must not be punished because of my inadequate and clumsy attempts to promote MSF. The estimated 1270 people each day (one every 68 seconds, a figure that will be one every 33 seconds by 2050) who develop Alzheimer’s disease and begin their descent into the darkness of dementia must not be forgotten. They must not become victims of incompetent attorneys and some bumbling university administrators who don’t know how to manage patents.
* * *
In an effort to remedy all the ills and deficiencies of the past efforts to take MSF to patients, a new venture, Brain-Tools, LLC, has been started. This endeavor circumvents the conventional channels that depend on patents. The key to development that is still open, and which will be used in this new effort, relies on the Orphan Drug Act of 1983 (US Public Law 97-414, as amended). The Orphan Drug Act was expressly designed by Congress to ease the costs and burdens of developing new drugs which promise benefits to society, but which have little or no potential for commercial success without some sort of government intervention.
The new venture to rescue MSF has now been founded and its objective is to get this advanced medicine to patients in the near future and at an affordable price. This new initiative is described in more detail in the POSTSCRIPT which follows.