Progress

Tuesday I had what may have been my first actual treatment for the brain rot that has been affecting me for the last four years or so.

My doctor calls it a "study."

The drug company calls it a "phase II clinical trial."

I'll call it, Progress

We (Lyn and I) spent most of the day going through this.  Lyn is an essential partner and participant in the study, required for me to qualify.

Tuesday I had a 3 hour 20 minute intravenous infusion of, well, something, not really sure what. This is the first of a series of about almost 20 such treatments over the next year.

But that was just part of the day.  I also had two EKGs (before and after), several psychological interviews, had eight vials of blood drawn for tests, peed in a jar. two blood pressure tests, and Lyn had a psych interview.

Over the last couple months, to qualify for the study and provide base lines for comparison, I also had exams, interviews, a brain MRI, a spinal tap (and another to patch the leak) blood and urine tests, and an EKG.

So, what am I being treated for, anyway?  That's hard for me to say (and you should have heard my speech therapist asking me three times to repeat it til she got it).

PSP?  What the heck is that?:

My latest diagnosis is something called "Progressive Supranuclear* Palsy" or "PSP." For someone with PSP, that's more than a mouthful. You could read more at this link: Cure-PSP about PSP

If you've seen me lately, you have a pretty good idea.  It messes with the cerebellum, the part of the brain that controls movement. So, I have trouble walking, talking, using my hands, even swallowing. My vision is affected by decreased eye muscle control.  Basically, the brain slowly loses the ability to to control the body.

PSP is grouped into Movement Disorders, of which Parkinson's Disease is by far the most common.

PSP is one of four major categories of "Atypical Parkinsonism," which share some symptoms with Parkinson's Disease:

• Lewy Body Dementia
• Multiple System Atrophy (MSA)
• Progressive Supranuclear Palsy (PSP)
• Cortico Basal Degeneration (CBD)

There's not much to choose among the four.  None of them are anything anybody would choose.  But, as the old joke goes, about the Alzheimer's patient, told by his doctor he had cancer, and then also told he had Alzheimers: "Well, at least I don't have cancer."

On the up side, the Atypicals generally do not include the tremor or shaking typical of Parkinson's.  On the down side,  they usually do not much respond to the carbidopa-levodopa ("Sinemet") that helps a lot with Parkinson's symptoms.  I take it anyway, but it is probably, mostly, placebo for me.  Hard to tell.

There are several other sort of similar brain disorders, including the probably better known ALS ("Lou Gehrig's Disease") of the recent Ice Bucket Challenge fund raising campaign, and physicist Stephen Hawking.

PSP, though rare, is actually a little more common than the better known ALS,  ALS is likely more well known because it tends to strike at a younger age.  The effects of PSP and ALS are similar in many ways.

Alzheimer's is not a movement disorder, but a memory and cognition disorder, attacking a different part of the brain, but by a similar mechanism.  Unlike Alzheimer's, PSP has little effect on memory or thinking.  I have not noticed any such effects yet, though they may come, but if I hurt your feelings, please blame it on the PSP effects.

Few people, even medical professionals, have heard of most of the movement disorders, except Parkinson's.  ALS seems to get categorized differently.  MSA often gets confused with MS, Multiple Sclerosis, which is quite different.

How did I get diagnosed?:

In California, I was seeing "Movement Disorder" specialists at both USC and UCLA.  There did not seem to be much incentive to try to put a specific name to my symptoms, as there are no real treatments for any of them, aside from dealing with the symptoms. My main specialist at USC  preferred to call it simply "atypical Parkinsonism."  When pressed to put a name it, he suggested probably MSA but there are  two or three sub-categories within MSA.

At UCLA, one of their movement disorder specialists thought I might have a different movement disorder, a genetic condition called "spinocerebellar ataxia,"  (another mouthful), but genetic tests pretty much ruled out any of the known genetic Ataxias.

This Spring, the Neuro-genetic specialist at UCLA, knowing I had moved to near Chicago, recommended a Movement Disorder specialist at Rush Medical Center, who she had worked with before and been impressed by, so I saw Dr. Deborah Hall at Rush in June.  Based on eye movements, gait, and speech characteristics, which had all progressed since the move from Los Angeles in the winter, Dr. Hall diagnosed my disorder as PSP.

This particular diagnosis is fairly new, only since June, and I was not convinced at first it was correct.  The fact that I was screened extensively for acceptance into the study seems convincing that it is.  I am just starting to learn more about PSP.  To be honest, I haven't wanted to focus on obsessing about what I may have, or make my condition the focus of my life. I am still learning about it.

So: What's with this treatment stuff?:

It happens that there is some possible recent progress on PSP treatment, due to advances in immunotherapy, using monoclonal antibodies to enlist the body's own immune system to fight the problem in the brain.  You may have noticed this week the Nobel Prize for medicine was announced for advances in using immunotherapy to treat cancer.

The clinical trial I have started is for a drug with the catchy name, ABBV 8E-12, which they are nicknaming ABBVie Arise (catchier).

Two drug companies, ABBVie and Bristol-Meyers-Squibb, are both working on immunotherapy monoclonal antibody treatments for PSP.  BMS also had a clinical trial, but the BMS monoclonal antibody was licensed by Biogen and their clinical trial has been withdrawn at this point, possibly some licensing issue.

PSP is so rare that there is little incentive for commercial drug companies to work on it.  That PSP is getting this attention seems serendipitous.  The general methodology might be applicable to the treatment of Alzheimer's Disease, which is far more common, and is their real target.  But Alzheimer's generally progresses more slowly, and is more complex, so, PSP may be a better test disease for the technology, as results could be measured in less time.  

There seems to be something in the brain cell neurons called Tau protein, that goes haywire in PSP.  Parkinson's Disease has a similar mechanism, but with a different protein (alpha-synuclein). These proteins get "misfolded", clump together, and their neurons die. The immunotherapy attacks the misfolded Tau proteins in between cells, to impede the problem's spread to other neurons. At least, that's the hope.  They have not yet found an immunotherapy for any of the other movement disorders, just PSP.  I maybe got a lucky break on the PSP in that regard.

This clinical trial I have just joined is a double-blind placebo controlled study. Three groups of patients get full dose, half dose, or placebo saline infusions.  Neither I nor my doctors know which group I'm in.  So, there is a 1 in 3 chance I'm just getting 20 doses of saltwater.  The study lasts a year.  I start out getting infusions every two weeks, then after several months, go to monthly infusions.  You can read read more detail on this link: Clinical Trials

After the one year blind study, there is a proposed 5-year extension study that would be "open label" where I could get the drug and know what I am getting.  Assuming, of course, that it actually works at all.

This trial expects to enroll 330 participants at 68 treatment locations worldwide (check for one near you).

Who pays for all this?

This research is astoundingly expensive.  I can only guess at the overall cost, but just for me, just for the screening to qualify into the trial, they paid for a brain MRI, a spinal tap, another spinal tap to fix the leak caused by the first, blood and urine tests, an EKG, and extensive physical, neuro and psych exams.

Each infusion includes the whole set of tests I had this Monday (not the MRI or spinal tap - those get repeated only at the end of the whole trial). Update: Turns out I do get another MRI this December.

This drug has qualified as an "Orphaned Drug," that would treat fewer than 200,000 patients in the US. There are an estimated 20,000 Americans with PSP, but only 5,000 actually diagnosed.  It is hard to diagnose. Orphaned drug research gets some tax breaks (less under recent Trump Administration regulations) because they are unlikely to be profitable.

For me, personally, the drug trial is free.  I don't have to pay for any part of it.  

The drug company is putting up much of the cost. 

Rush Medical Center, and my doctor, get research grants and funding that help pay for some of the cost.

And contributions from organizations like Cure PSP also help with seed money that gets research like this started.

Will it actually benefit me?

Possibly:

• If the treatment actually works (uncertain - that's why they do the double blind study).
• And, if I am in the two groups actually getting the treatment, not the placebo control group.

I'm trying to keep my expectations realistic.

If the treatment works, it would slow the progress of the disease in taking away my ability to move.  It would not repair the damage already done to my brain.  It is unlikely to entirely stop more damage from happening.  But, compared to treating the symptoms while they get steadily worse, that would be a whole lot. 

Even if I am in the placebo group, after a year, if it works on the other groups, I could get it too, so that's reassuring.

I don't think the researchers expect that this would stop the disease entirely. They are cautiously optimistic that it may slow the rate at which new brain damage progresses.

It's Progress; not a cure:

The most likely scenario is that this is a major step toward developing a truly effective treatment.  Whether this actual treatment method works or not, progress is being made, things are being learned, methods being refined, that will help develop better treatments.

A lot more expensive research is needed to get to a real cure for these brain disorders.

A positive is that progress on one brain disorder may help with others.  What is learned with PSP may help with Alzheimer's, and what is learned about Parkinson's may help with PSP.

But, the diseases that affect the most people understandably get the most attention.  Michael J. Fox, Muhammad Ali, and Davis Phinney get a lot of money devoted to Parkinson's Disease, and that's great.  The "atypicals" get the crumbs that fall from the Parkinson's table. I'm not jealous.  The priority for the more common diseases is reasonable.

Still, this immunotherapy treatment is more progress than has been made on any of the other movement disorders.  I'm really excited that that this trial is happening.  Six months ago, I thought there was no treatment at all, just managing the symptoms.

Real, concrete, optimistic, progress.

If you care to contribute:

I have checked out this Cure PSP organization.

This organization is real.  It is efficient.  It is effective.  My doctor goes to its fund raisers.  It really is helping. And it obviously is not spending a lot of money on advertising or self-promotion.

You can donate through my Facebook post here:Facebook post

Or on the Cure PSP Website here: I Want To Help

There's a lot more I could say, but this blog post is already too long.  More some other time.

*(Notice special pet peeve from this old nuclear engineer, that "Nuclear" should be pronounced as it is spelled:  New-Clee-Ar.  NOT:  "Nuc-Yu -Lar".  Likewise it is surpra-new-clee-ar,  Not supra-nuc-yu-lar)