Excerpt 5 – The First Volunteers – 1995
My Journey to a
Next Generation Treatment
Donald E. Moss, Ph.D.
[Setting and Summary by Jim Summerton, Ph.D.]
[ Setting and Summary: By mid-1995 the initial possibility of an affordable clinical trial in Mexico was becoming a reality - enabled by a $50,000 grant from the Coldwell Foundation of El Paso, and through an invaluable collaboration with Dr. Pati Berlanga, a geriatrics clinician in the City of Chihuahua. Once the appropriate review boards and regulatory agencies had all signed off on the proposed clinical trials to be carried out in Chihuahua, the next key step was to initiate the Phase 1 safety trial by recruiting normal test subjects, as described in this chapter. ]
When Mary and I met with Pati the following morning, we learned that she hadn’t heard anything from either of the committees reviewing our planned undertaking. That they hadn’t asked any questions or raised any new concerns was probably good news. It would be another week before they would meet. I didn’t mind that delay because I didn’t feel like I was ready to start. There were many details about running the lab that had to be worked out and adapted to the clinic. The project would certainly fail if I didn’t have reliable lab results.
MSF was not like tacrine (Cognex7). The dose of that cholinesterase inhibitor was determined by increasing the amount given to the patient until they began to throw up and have diarrhea.
The whole reason for developing the far-higher-specificity MSF was to completely avoid these highly undesirable side effects. Patients taking MSF could be grossly overdosed before they began to show side effects. Therefore, I had to figure out the right dose by some measure other than seeing when the patients couldn’t tolerate any more.
The effect of MSF on red cell AChE would have to tell me the correct dose. I couldn’t take brain biopsies in my humans like I’d done with my monkeys. The monkey experiments had, however, shown me how AChE inhibition in the blood could be used to estimate the effects in the brain.
The bottom line was that I had to have absolutely reliable measures of AChE activity in human red blood cells to have a successful and safe experiment. Red cell AChE was my only window on the brain.
To be sure my lab was set up and running correctly, I used myself as my own standard guinea pig. After a few days of getting my veins poked and jabbed, it was clear that I had to adapt the procedure to tiny samples of blood taken by finger-prick. I was sure my volunteers would be happier, too. The new procedure involved pricking a finger and drawing up a minuscule drop of blood into a glass tube the size of the lead in a pencil.
To be accurate, I had to know the exact amount of blood in the tiny tube. When I tried to weigh the blood in the tube, my balance didn’t give me consistent results. Air currents in the lab and vibrations in the clinic floor affected the readings. I wished that I had the three pieces of steel pipe I used as the table for my balance in El Paso. But they were too damned heavy to get in and out of my car.
I knew that I could make a good table if I could find some cinder blocks. That’s how it came that during lunch time one day, Hugo, Mary, and I went out and stole some cinder blocks from a construction site. The problem was solved.
After a week of these standardizing experiments on myself, the results were rock solid and we were ready to begin.
* * *
On Tuesday, June thirteenth, Pati came running down the hallway from her office at the back of the clinic and burst into the lab smiling. She insisted that we stop what we were doing and come to her office.
Once Hugo, Mary, and I got situated in the overstuffed chairs around her desk, Pati told us that she’d just received a phone call. The chairmen of the Faculty of Medicine informed her that the Comité Etica and the Comité de Investigación had both met and approved the MSF project. Official letters would be sent to Pati with copies forwarded to the Secretary of Health in Mexico City. We could begin.
After we realized that we were free to start, we settled down to reality, Pati laid out a plan for recruiting the healthy people we needed for the first step. She was a member of a book club made up of people about her age. She hosted the group one Thursday evening per month in the reception area of the clinic. They might volunteer as a group and they would be meeting that week, in two days. Would I like to make a pitch to them and see if we could get some volunteers?
I could hardly contain the excitement I felt at how fast we were moving. We actually had regulatory approval and possible volunteers, all within ten days of coming back to Chihuahua.
Together, the four of us planned a presentation to ask for their participation that night. Hugo and Mary would add information about MSF as we went along. As a native of Chihuahua, Hugo knew some of the people. And Pati’s sister, Ana, was a member of the group and she knew about MSF from being with us at the clinic and talking about it. To alert the book group about what we were going to ask them to do, Pati would send out an e-mail so they could think about it beforehand. Secondly, if anyone volunteered, we’d have the lab set up and Hugo and Mary would be ready to process any blood samples we might collect that evening.
* * *
Two days later, Thursday night at eight o’clock, just as the clinic was closing and the last patients were going home, the members of the group began to arrive. As Pati and I greeted everyone at the door I couldn’t keep visions of my earlier disasters in Argentina from bubbling up in my mind.
Within a few minutes, the reception area was filled to overflowing with the twelve members of the group that included Pati and her sister Ana. As Mary and I were introduced to all of these new people, Hugo brought some extra chairs from the back of the clinic. In the midst of all this, Pati’s secretary set out some coffee and cookies, closed up the clinic, and left for the day.
There was a general hubbub as the members greeted each other and caught up on personal news. The eight women and four men ranged from thirty-seven years old, slightly younger than Pati’s thirty, to one person sixty. I fit right into the group at age fifty. All of them were well dressed professionals, most coming to the meeting at the end of their normal Thursday routines.
I began to relax as they laughed and bantered with each other and several wanted to talk to me. As I found out more and more about them, I realized that this was a special, highly educated and active group that included community leaders, successful business owners and an attorney.
The room was so crowded that Mary and Hugo watched from the doorway to the lab. Once all of the guests had some refreshments and had found a chair, Pati started the meeting by introducing everyone to me again, although remembering all their names
was hopeless. She then gave a short summary of how she and I had met and how MSF might help patients with dementia.
To underscore the importance of what we were trying to do, she mentioned that although tacrine had been approved in the U.S., no drug had been approved in Mexico and families were desperate to get some treatment. With that introduction, Pati turned the meeting over to me.
I stood at the edge of the circle of people, between Pati and Ana, where I could see everyone, and started my discussion about MSF with why I was in Mexico. I’d practiced the Spanish I needed for that and I had some notes to guide me. Without a patent, I explained, there was no way for anyone to make any money from MSF, including Pati and me, and tests in the U.S. were impossible because of the huge costs. Emphasizing that I was not there just to use them for conejillos de Indias, I also told them that I’d taken the drug myself. I saw people smile and nod their heads and I was interrupted with a few questions.
The second part of my talk focused on MSF, Alzheimer’s disease, how they fit together. I gave a short review and why MSF might be an effective treatment. I had hardly started that topic when several people began to pepper me with questions that went beyond the superficial summary that I had planned. This group seemed to be the complete opposite from the people I’d met with in Argentina. Pati’s study group understood the technical aspects of what I was saying and they were thirsty for more.
Even though I’d been derailed from my prepared remarks, the questions I’d been asked and the comments people were making to each other made for a good but disorganized summary of the project in a friendly atmosphere.
After an hour, I wrapped up by emphasizing the importance of having healthy people take the drug as the first step. If healthy people were not willing to take a risk to help others, all would be lost. Lastly, I asked if there were any other questions.
Everyone seemed satisfied and there was an air of excitement about being part of something important. Riding the jubilance that rippled through the room, it was time to ask. “Would anyone volunteer to take MSF?”
The question was no more out of my mouth when Ana jumped out of her chair and declared that she wanted to be number one. A second lady volunteered so quickly that Pati slipped to number three before she could put her name on the list. To my delight, within a few minutes everyone in the group had signed up and we were up to number twelve. I then put my name on the list as number thirteen.
More coffee and cookies were served as Mary and Hugo passed out the consent forms that stated that the people had to be healthy and that the women could not be pregnant or likely to become pregnant. The form also listed all possible side effects, including the rare possibility that someone might die. It also included a bunch of legalese stating that no one would be responsible for any injuries. It also said that no one would receive any pay for participating and that anyone could withdraw from the trial at any time, for any reason.
There were, as expected, additional questions as people read the forms and both Pati and I answered them as fully as we knew how. To my surprise, one person after another signed the form until everyone on the list had given consent.
There was a party atmosphere as each person turned in their form and were then ushered into the adjoining lab. Mary and Hugo took turns pricking each person’s finger for the first of the three baseline blood samples that would have to be taken before anyone would be given the first dose of MSF.
* * *
At two o’clock the following morning, long after the last volunteer had gone home, Pati, Hugo, Mary and I finished analyzing the blood samples we’d collected. Too excited to go home and go to bed ourselves, Pati served hot chamomile tea and we talked about the evening for another hour.
That night, June fifteenth, 1995, twenty five years after the offhanded discovery of sulfonyl fluorides in an old freezer at Colorado State, I realized that Pati, Hugo, Mary and I were taking the first tangible step toward getting MSF to demented patients. As Mary and I walked back to the apartment that night, I looked up at the nearly full moon that was still making its way across the night sky and tried to convince myself that the tests had started.