Exciting New Research

(all photos by Jennifer Chase)

I was chosen as a patient fellow for the ALS/MND International Symposium in Boston in early December. I was looking forward to learning a lot and meeting researchers and the other patient fellows.

The day before we were going to fly across the country to Boston, my husband, Stan, was hospitalized with life threatening septic shock. This forced me to cancel my trip to the conference.

But through social media and the ALS/MND International Symposium phone app, I got a message from a woman named Jennifer Chase, who has the C9ORF72 gene mutation like me. Jennifer lost her mom (who had FTD then ALS) and sister to ALS and her sister was one one of the first commercially tested patients confirmed to have the C9ORF72 gene. Jennifer is a brave sister in that she decided to get tested herself. She does have the gene mutation and has been learning all she could since finding out and she has been participating in research studies. She was attending the meeting on her own and she agreed to send me photos and updates. I appreciate her so much because she allowed me to learn through her eyes. What follows is a summary of the updates she sent me.

the registration table

There was a display of ALS/MND patients from all represented countries, including the awesome Osiel Mendoza from the USA.

Jennifer also sent me a photo of the registration swag.

The swag included the Nature Outlook from which I quoted two weeks ago

And now her report on the first day:

The Opening keynote speaker, Dr. Jeffery Rosenfeld from Loma Linda University, spoke about the need for a new paradigm: the need to define and stratify as done in MS, epilepsy, and headache. Even if lines are drawn wrong at first it’s time to start. He also said that biomarkers are what need to be tracked in clinical trials. The patient’s functional rating scale (FRS) doesn’t give results quickly enough.

Then there were awards:

  • Humanitarian award to the guys that started the ice bucket challenge – Anthony Senerchia, Jr. (awarded posthumously), Patrick Quinn, and Pete Frates. Pete’s mom Nancy accepted the award.
  • Forbes Norris Award to Dr. Merit Cudkowicz of Massachusetts General Hospital (and Jennifer’s neurologist) for her passion in researching and caring for patients with ALS and finding the cure.
  • The Paulo Gontijo Research Award to Marta Van Blitterswijk, MD, Ph.D of the Mayo Clinic in Florida for her work attempting to understand the variability among patients with ALS, including age at which it starts, presence of dementia, diesease progression and survival. Most of her patient centered work has focused on the C9ORF72 mutation.

Then Jennifer sent me this photo of ALS TDI researchers. The two on the right are working on C9ORF72 research

She said the rest of the morning was good, although nothing specific to C9 was covered. The Symposium registration was the highest ever – 1281. The scientific sessions were packed. She even saw people on chairs outside the rooms. She said she thought there were slightly more people with ALS there than 2 years ago.

The first afternoon session had a lot about the nuclear pore membrane and C9ORF72. One of the sessions was about SRSF1 (a protein coding gene and nuclear export adaptor) and C9 as a potential way to block the deleterious C9 while allowing the good C9 to work. They are looking at three potential approaches in fruit flies.

She walked through the posters not during the poster session, because of being too tired – I know I would have been exhausted . She noted one that described ALS as the nice person’s disease, and the poster said it looks like some truth to that because the characteristics that make people with ALS nice may be associated with risk factors in lifestyle and occupation.

She went to the clinical trials session on Friday afternoon.

  • Mastinab – normal progressors with less than a 1.1 decline on their FSR showed a slowing of decline at highest dose. There are reports of study irregularities though.
  • Tirasemtiv failed but a related drug is still in trial.
  • Ibudilast – Jennifer said it was confusing. She said they are hoping it slows FSR decline but it needs more study.

Moving on to the Saturday morning session, there was a hopeful presentation on a mechanism to help drugs bypass the blood brain barrier.

She said the biggest deal was Frank Bennett who is Vice President of Research for Ionis, in Carlsbad, CA, which is one of two companies developing the antisense drug. It is already being tested on ALS patients with the first gene defect identified – SOD1 and Bennett said the trial is going well. He also showed a video of kids with Spinal Muscle Atrophy who have been treated and the results were amazing – they were able to meet developmental milestones that untreated patients never could.

Another takeaway was from a presentation from Dr. Michael Benatar of the University of Miami who has been doing pre-familial ALS research – there may be a biomarker sometime that can detect disease before it is obvious clinically which would be a window for treatment for carriers. That would be very exciting.

C9 ALS normally has an average progression rate, but there are subsets – one where there is little progression for years (10 or more years) and another subset where progression is brutally fast. The doctor who was doing extensive genotyping discovered that these brutally fast progressors have a “rare deleterious variant” of the C9 mutation – they all died within a year.

Jennifer also went to Dr. Nick Maragakis’ presentation on excersise. She said basically supervised exercise (stretching, resistance, or cardio) did not hurt the study group but it not help ALS either. But I know from experience that exercise can help quality of life.

Then on to Sunday, the last day. She said there was lots on basic C9 research. Dr. Marka Van Blitterswelk (who won the research award) spoke about her findings on post mortem studies of C9 FTD with and without ALS. It was all good science and increased understanding. This work could not have been completed without the brave C9 patients who donated their brains, and their brave families.

Dr. Nazem Atassi presented on a PET MRI study which is not C9 specific but he thinks it can be used for smaller, faster phase 1 and 2 trials because it has a strong signal.

Dr. Brown giving the closing remarks

The closing session speaker was Dr. Robert Brown, of UMass Memorial Medical Center in Worcester, MA, who has been studying ALS with a special interest in genetics for a long time. He said the C9 antisense trial will be coming up in late 2018 (although I have since heard it may be sooner, and I hope to participate).

I had two comments from family caregivers from my blog requests before the conference.

The first one is from the sister of an ALS patient in California. He was diagnosed in March with familial ALS. After finally getting approved for Radicava he changed his mind so he could apply for the Nurown Phase 3 stem cell trial, and one of the requirements was to not be taking Radicava in the 30 last days. His breathing is also declining quickly and he won’t qualify for the trial if his breathing is below 60 percent Forced Vital Capacity. His sister would like to see changes in trial criteria. Why should a patient have to give up a promising treatment to participate in research? Of course trials are controlled scientific studies but it can lead to very frustrated patients and families.

I too have had frustrations with clinical trials. Many of them exclude patients with feeding tubes. That makes me think that the drug being tested might not be available to patients with feeding tubes.

Cathy Collet, a patient fellow committee member, reported that neurologists are skeptical about Radicava’s efficacy because of the small clinical trial, but glad to have it in their tool bag. I am taking a break from Radicava treatment to sort out unwanted side effects or whatever is causing my sinus problem.

The next comment was from the daughter of an elderly ALS patient in Canada. She is frustrated by the lack of studies on geriatric patients, and the tools to explain feeding tubes and suction to an 88-year-old. She also has observed that weight loss and slurred speech in the elderly is usually attributed to stroke. Cathy Collet said there was no mention of diagnosis in the elderly, and that is near and dear to her heart because her mother was diagnosed in her 70’s. It is an issue that sorely needs to be addressed.

I am sorry that I was not able to attend but I am so appreciative of Jennifer and Cathy for sharing information.

Background on my genetic mutation causing ALS – C9ORF72 

I am doing something different in this blog. In two weeks I will be blogging about the ALS/MND International Symposium in Boston for which I was a patient fellow but could not attend due to a family emergency. A wonderful woman named Jennifer Chase, who has the same gene mutation as me, contacted me and offered to send photos and summaries from the conference. She had the same focus on this gene mutation as me so that is the research she mainly reported on. I thought it would be good give you the background on this genetic mutation before reading the conference summary. Next week I promise the end of the Hawai’i trip and our recovery and prep for Jonika and 18 month old Ollie visiting as well as their arrival. 

Here is a great summary from the jounal Nature, from their Nature Outlook: Amyotrophic Lateral Sclerosis 

Genetics: The hexanucleotide hex
by Elie Dolgin

For years, researchers missed the most common genetic cause of ALS. Now they’re on an accelerated track to treat it.

Mark Price’s family had a long history of neurological disease. His sister and uncle had died from amyotrophic lateral sclerosis (ALS), and his mother and aunt were living with dementia. But it was not until Price himself started to slur his words in 2010, shortly after his daughter Sharon’s wedding, that it dawned on him that there might be a genetic basis to his family’s tragic medical past.

Within a year, Price was diagnosed with ALS, and Sharon wondered if she — or her future children — would be next. “I stopped everything and said, ‘I can’t have a kid until we figure this all out,’” recalls Sharon, then aged 26. At first, Price’s doctors couldn’t pinpoint any defects in the ALS-associated genes that were known at the time. Then came reports in September 2011 that two teams of scientists had found a new gene linked to ALS, one that could explain up to 40% of familial cases of the disease and 10% of what are known as sporadic cases. What’s more, this gene accounted for an estimated 30% of hereditary cases of a condition known as frontotemporal dementia (FTD), providing a long-sought genetic rationale for why that neurodegenerative disorder often struck members of families affected by the motor neuron disease ALS — families such as Price’s.

Mark Price, here in a family snapshot with his daughters in 1988, was diagnosed with ALS in 2011 and found to carry a faulty C9ORF72 gene.

The genetic culprit is called C9ORF72— from its location on chromosome 9 in a region known as open reading frame (ORF) 72. And it has an unusual nucleotide sequence pattern. In some people with ALS or FTD, a short stretch of DNA in a non-coding portion of C9ORF72 is repeated hundreds or even thousands of times; in healthy individuals, the same sequence — GGGGCC — is repeated fewer than two dozen times.
In early 2012, Price was tested for the C9ORF72 repeat expansion. The test came back positive, and he died a year later. And while Sharon and her two sisters grieved for their father, they also had to grapple with the fact that each of them had a 50:50 chance of carrying the genetic defect. Now, they had to decide — would they get tested?

House hunting

The story of C9ORF72 starts with the German psychiatrist Anton von Braumühl, who in 1932 first made the link between ALS and FTD. But it was not until the mid-2000s, when the genetics of large multi-generational families affected by both disorders were studied, that researchers began to zoom in on the short arm of chromosome 9 as harbouring the gene of interest. By 2010, they had narrowed the search down to a stretch of 232,000 nucleotides — tiny by genomic standards. But none of the four genes in that region contained any protein-altering mutations that could explain the disease connection.

“It’s like we knew the street, but we didn’t know the exact house,” says Ammar Al-Chalabi, a neurologist and clinical geneticist at King’s College London.

The race was on to find the gene responsible. At least five research teams from across Europe and North America dedicated themselves to solving the problem. Many thought it would be straightforward. But C9ORF72 proved to be “very sneaky”, says Ekaterina Rogaeva, a molecular geneticist at the University of Toronto in Canada. “This region is not user-friendly.”

A group led by Rosa Rademakers, a neurogeneticist at the Mayo Clinic in Jacksonville, Florida, focused on a three-generation family in which ten individuals had ALS, FTD or both. Not knowing what to search for in these patients’ genomes, “we looked for anything that might be suspicious”, Rademakers says. That included the GGGGCC-rich section of C9ORF72.

She and her colleagues set up polymerase chain reactions (PCRs) to amplify that region and saw an unusual inheritance pattern: for everyone in the family who had a neurodegenerative disease, the PCR test showed them having two identical copies of C9ORF72 when they should have had different variants.

It was a head-scratcher for Rademakers until it dawned on her that the genetic defect was larger than the upper size limit that the PCR could read. She and her collaborators turned to a more sensitive technique called repeat-primed PCR and observed a large repeat expansion — but only in affected family members. None of their unaffected kin had it. Nor did some 1,000 healthy controls.

The researchers tested another 696 people with ALS or FTD to make sure that this repeat was not unique to the family they had studied. Sure enough, they found the C9ORF72 mutation in another 59 unrelated individuals, including 22 who had no known family history of neurodegenerative disease. Further experiments showed that the GGGGCC stretch repeated itself at least 700 times.

“Wow,” Rademakers remembers thinking. “This is something that’s going to have consequences.” At the same time, an international consortium led by Bryan Traynor, a neurologist and geneticist at the US National Institute on Aging in Bethesda, Maryland, was making the same discovery. Traynor was clued in to the repeat expansion by the technical shortcomings of a different DNA analysis method — next-generation sequencing. “It was an amazing moment sitting in front of that computer and knowing what was truly going on there,” he says.

The two teams published their results back-to-back in September 2011 in Neuron, beating other groups that were still on the hunt for it. “We were scooped,” says Al-Chalabi. “But in a sense, we were pleased to be scooped.”

In vitro fertilization has enabled Price’s daughters Sharon Stone (left) and Jodie Price to avoid passing on the faulty gene to their children. Image: Sarah Keayes/The Photo Pitch

Exciting times

The discovery had an immediate impact. The frequency of the C9ORF72 defect in patients “made everyone who’s seriously interested in ALS feel like they should work on it”, says Pamela Shaw, a neurologist at the University of Sheffield, UK.

Brian Dickie, director of research development at the Motor Neurone Disease Association in Northampton, UK, recalls flying from London to a meeting in the United States that September. It was five days after Rademakers’ and Traynor’s papers were published. Several ALS researchers and clinicians were on board and someone had printed copies of the manuscripts. “They were being passed around the aircraft as we were flying over,” Dickie says. “It was clearly an exciting time.”

Several drugmakers jumped on the finding. “It was difficult to ignore something like the C9ORF72 discovery,” says Brian Zambrowicz, head of functional genomics at Regeneron Pharmaceuticals, a company in Tarrytown, New York, that was founded to tackle neurodegenerative diseases, but broadened its strategy 20 years ago after its first drug candidate failed to help people with ALS. According to Zambrowicz, the discovery of C9ORF72 prompted the company to focus again on ALS therapies, starting with the creation of a C9ORF72 mouse model.

Ionis Pharmaceuticals, which specializes in antisense RNA-based therapies that can switch off disease-causing genes, also moved rapidly. “We put a plan together the day the papers came out,” recalls Frank Bennett, senior vice-president of research at Ionis, based in Carlsbad, California. Within two years, Bennett and his academic collaborators had demonstrated that an antisense drug could reduce aberrant C9ORF72 mRNA levels in cell cultures. They had proof-of-concept data in mouse models a little more than two years later. A lead drug candidate from Ionis is now undergoing preclinical toxicology studies, and human trials could begin early next year.

That speed, says Lucie Bruijn, chief scientist at the ALS Association in Washington DC, was enabled in part by the influx of investigators driven to deduce the mechanism by which the C9ORF72 defect causes disease. The repeat expansion recalled those found in other neurodegenerative disorders, including Huntington’s disease, myotonic dystrophy and spinocerebellar ataxia. In addition, it overlapped genetically with FTD. Researchers who study these brain diseases had historically worked in isolation. After the C9ORF72 discovery, they came together with a common purpose.

“We suddenly had a large number of clinicians and scientists interested in ALS,” Bruijn says. “That gave the field an enormous boost.” The first idea about why the GGGGCC mutations might cause ALS or FTD had less to do with the repeat expansion and more to do with the normal C9ORF72 protein. Rademakers noticed that levels of the normal protein were reduced in people with the gene defect. Although the protein’s role is still poorly understood, it is thought to be involved in the transport of molecules within cells. Rademakers’ observation led to the suggestion that lower levels of normal C9ORF72 could be driving pathological brain responses.

Initial studies seemed to refute this hypothesis. Mice with little or no expression of the C9ORF72 protein in their neurons displayed no behaviours indicative of a neurodegenerative disease, and nor did their brains have the molecular hallmarks of ALS or FTD. More recently, however, several teams have noticed immune defects in mice that lack C9ORF72 in all tissues. Together, these findings indicate that the lower levels of working C9ORF72 do not themselves cause neuron degradation, although the altered immune responses could add to the severity or progression of the disease. “It may contribute,” says neuroscientist Jeroen Pasterkamp at the University Medical Center Utrecht in the Netherlands, “but in conjunction with other mechanisms.”

No gain, no pain

The most obvious alternative mechanism is RNA toxicity. Other diseases caused by non-coding repeat expansions are explained by aggregations of aberrant RNA in the nucleus that bind and sequester housekeeping proteins that are otherwise needed for proper cell function. Pursuing this hypothesis, molecular neuroscientist Adrian Isaacs and his colleagues at University College London created transgenic fruit flies to test whether these aggregates caused disease. They were in for a surprise.

Flies with more than 100 GGGGCC repeats did indeed show signs of C9ORF72-mediated neurodegeneration — but only when the repeat-containing RNA could be translated into a protein, and not when the RNA was interspersed with translation stop signals. RNA aggregates, in other words, were not enough to cause disease. Rogue proteins seemed to be the real drivers. “I was convinced the flies would tell us it was an RNA toxicity,” Isaacs says, “but when we saw the data it was clear that that was not the case.”

The proteins that emanate from the GGGGCC expansion are created through an unusual process that does not require a start signal and can occur even with repeat sequences located in non-coding gene regions. Laura Ranum, a neurogeneticist at the University of Florida College of Medicine in Gainesville, first described this phenomenon in 2010, in tissues from people with spinocerebellar ataxia and myotonic dystrophy, and in mouse models of these diseases.

According to Ranum, the research community initially largely ignored her findings. Many doubted that the mechanism was real. Then came the RNA-binding Proteins in Neurological Disease symposium in November 2011 in Arlington, Virginia, where Rademakers and Traynor discussed C9ORF72 and Ranum spoke about the unusual form of protein translation. Scientists quickly connected the dots.

Dieter Edbauer recalls sitting in the audience, listening to Ranum’s talk, and pulling out his laptop to see what kinds of protein the C9ORF72 expansion might make. Because the repeat is six nucleotides long — and protein synthesis relies on a triplet code — Edbauer realized that C9ORF72 might yield a handful of different proteins, each containing two amino acids repeated over and over again. He typed out each of these potential dipeptide repeat proteins. “I looked left and right to see if somebody saw what I did,” recalls Edbauer, a molecular neuroscientist at the German Center for Neurodegenerative Diseases in Munich. “I thought that everybody must have had the same idea, but apparently not.”

Fifteen months later, in February 2013, Edbauer and colleagues reported that these proteins accumulate throughout the brains of C9ORF72-affected people. Within days, Rademakers and her Mayo Clinic colleagues, led by molecular neuroscientist Leonard Petrucelli, published similar findings, as did Ranum herself before the year was out.

Since then, evidence has mounted that at least some of these repeating proteins are “uniformly wicked toxic”, says Paul Taylor, a molecular geneticist at the St Jude Children’s Research Hospital in Memphis, Tennessee. These proteins seem to cause neurodegeneration by snarling up the trafficking of molecular cargo between the nucleus and cytoplasm in brain cells. “The core defect in C9ORF72 is really that nuclear transport,” says Jeffrey Rothstein, a neurologist at the Johns Hopkins University School of Medicine in Baltimore, Maryland.

Call to account

Some researchers are now willing to pin the blame for C9ORF72-mediated disease entirely on these problematic proteins. “I won’t mince words here: the toxic poly-dipeptides do not contribute to the disease, they account for the disease,” says Steven McKnight, a biochemist at the University of Texas Southwestern Medical Center in Dallas. McKnight describes RNA aggregates and decreased normal C9ORF72 protein levels as “sideshows”.

“The evidence is pretty overwhelming that it’s the protein that’s toxic in these simple model systems.”

But most researchers are more equivocal. “The evidence is pretty overwhelming that it’s the protein that’s toxic in these simple model systems,” says Aaron Gitler, a molecular neuroscientist at Stanford University School of Medicine in California. However, he adds, “in the context of human disease it could be some combination of factors, and I have to keep an open mind.”

The debate over disease mechanism is not purely academic: it guides drug development. Some companies, including Neurimmune of Zurich, Switzerland, and Voyager Therapeutics of Cambridge, Massachusetts, focus just on blocking the repetitive proteins or preventing their formation, whereas others, such as Karyopharm Therapeutics of Newton, Massachusetts, hope to mitigate defects in nuclear transport without targeting any C9ORF72 gene products directly.

But some therapeutic strategies, such as antisense, do not depend on what the mechanism actually is. Because antisense drugs can shut off the production of both RNA and proteins, it does not matter which one is the causative agent in brain cells, says Paul Bolno, chief executive of Wave Life Sciences in Cambridge, Massachusetts, which is on track to start testing a C9ORF72-targeted antisense therapy in patients next year. And because you can track levels of the repeat proteins in the spinal fluid, it is straightforward to assess whether the drug is working. “You do have a measurable biomarker,” Bolno says.

Given how far researchers and drug companies have come in such a short time, it’s entirely possible that an effective therapy for C9ORF72-mediated disease will be available if more of Mark Price’s relatives start to develop symptoms of neurodegeneration. Haley, his youngest daughter, finds that prospect encouraging. “Hats off to the scientific community,” she says. But she worries that policymakers aren’t doing enough to support preventive health measures available today, to help avoid C9ORF72-related disease in the first place.

For family-planning purposes, Haley and her sisters all opted to find out their C9ORF72 status soon after their father tested positive. “Unfortunately,” says Jodie, the oldest, “it was bad news for everybody.” Each sister has since gone through multiple rounds of in vitro fertilization with the added step of checking that the embryos were free of the C9ORF72 defect ahead of implantation. It was emotionally, physically and financially taxing on everybody, costing at least Aus$150,000 (US$120,000), they estimate. Ultimately, however, “it was a confirmation that the science worked, and we could get rid of the family curse”, says Haley.

Sharon’s son Jack recently celebrated his third birthday, Jodie is expecting a daughter in mid-November, and Haley has two frozen embryos, ready to use after her wedding on 9 December.

This article is part of Nature Outlook: Amyotrophic lateral sclerosis, an editorially independent supplement produced with the financial support of third parties. You can find the whole article here:

 https://www.nature.com/collections/dmpwblhnbt

The Best Laid Plans (again)

​The best laid schemes o’ Mice an’ Men 
Gang aft agley,

An’ lea’e us nought but grief an’ pain,

  For promis’d joy! 

From Robert Burns To a Mouse 

Source:The Poetry Foundation 

This poem was most famously used by John Steinbeck in the title of his book  Of Mice and Men. The modern version of this quote is The best laid plans of mice and men will often go awry.

Well both Robert Burns’ version and the modern version of that quote fits my Patient Fellows experience for the ALS/MND International Symposium in Boston. It was all planned as a great trip with visits with relatives and dinner with the Patient Fellows who I have gotten to know in conference calls and emails and social media, and also a water workout with the amazing ALS athlete Andrea Peet. The day before we were supposed to fly to Boston, my husband, Stan, got a high fever and ended up in the Emergency Room with severe sepsis. So obviously we had to cancel our trip. Septic shock is life threatening and we got Stan to the hospital just in time, thanks to good friends I was able to text and who came right over and took over.  They called 911 and helped me get Stan’s bipap ready to take with us.

He was in the hospital for a week and it shook me to the core that he almost died. And it was hard on our son getting ready for Junior year final exams.

Stan survived thanks to antibiotics. And “what doesn’t kill you makes you stronger” is usually true. However, it is his medications for his Sarcoidosis that are making him susceptible to infections. Long term prednisone use weakens the skin and his wounds don’t heal without intervention. Unfortunately he will now have to stop taking Humira, which was our best hope for getting him off prednisone, and that is terribly disappointing.

But back to the Patient Fellows experience. Through the ALS/MND International Symposium meeting app on my phone, another woman who has the C9orf72 gene mutation messaged me. When I told her I had to cancel she agreed to send me updates throughout the conference. She loves science and loves to write, so her updates were great and I will be able to share her insights. Also, one of the patient fellow committee members will be sending me notes on some of the sessions I wanted to attend. So I will be able to do a blog about the meeting without having been there.

For the people who contacted me with comments for researchers, I was able to forward them to one of the Patient Fellows group members. So hopefully I will be able to address your concerns.

I was disappointed to not visit Aunt Candy and Uncle Bill, nor my godmother Alice, nor my cousin Len. I was really looking forward to seeing them.

However I also got antibiotics for a sinus infection this week, and I got handicap license plates due to my shortness of breath and the progressive nature of my disease. That will be a big help with my shortness of breath and carrying my portable cough assist and suction.

It was difficult single parenting my 17-year-old while Stan was in the hospital. But wonderful friends brought food for Andy and Erika came and stayed one night and my dad ran errands for me.

I started Round three of Radicava on Friday and will finish this round in Las Vegas on Christmas Eve, where we will spend Christmas with Stan’s dad and step mom.I am still able to care for my houseplants and my jade plant is blooming! That makes me happy.

We had a happy early Christmas celebration with my dad and Anita Friday night and that also made me happy.

We are blessed with great friends and great family. Happy Holidays to all, and especially all people with ALS and their families.

Through the holidays I will plan a blog post every other Monday, so my next post will be New Years Day. Here’s to breakthroughs in ALS in 2018.

I will end with another Robert Burns poem.

Should auld acquaintance be forgot,
And never brought to mind?
Should auld acquaintance be forgot,
And auld lang syne?

For auld lang syne, my dear,
For auld lang syne,
We’ll tak a cup o’ kindness yet,
For auld lang syne.

And surely ye’ll be your pint-stowp,
And surely I’ll be mine!
And we’ll tak a cup o’ kindness yet,
For auld lang syne.

For auld lang syne, my dear,
For auld lang syne,
We’ll tak a cup o’ kindness yet,
For auld lang syne.

We twa hae run about the braes,
And pu’d the gowans fine;
But we’ve wandered mony a weary fit
Sin’ auld lang syne.

For auld lang syne, my dear,
For auld lang syne,
We’ll tak a cup o’ kindness yet,
For auld lang syne.

We twa hae paidled i’ the burn,
Frae morning sun till dine;
But seas between us braid hae roared
Sin’ auld lang syne.

For auld lang syne, my dear,
For auld lang syne,
We’ll tak a cup o’ kindness yet,
For auld lang syne.

And there’s a hand, my trusty fiere,
And gie’s a hand o’ thine!
And we’ll tak a right guid-willie waught
For auld lang syne.

For auld lang syne, my dear,
For auld lang syne,
We’ll tak a cup o’ kindness yet,
For auld lang syne.

Auld Lang Syne a Christmas & New year poem by Robert Burns
Source: https://m.carols.org.uk/auld_lang_syne_burns.htm

Folsom Prison Blues

Johnny Cash played at Folsom Prison four times in the late 1960’s and early 1970’s


Folsom Prison by Johnny Cash

I hear the train a comin ’round the bend
I ain’t seen the sunshine since I don’t know when
Well I’m stuck in Folsom Prison and time keeps dragging on
While a train keeps a rollin’ on down to San Antone

Well when I was just a baby my mama told me son
Always be a good boy don’t ever play with guns
Well I shot a man in Reno just to watch him die
When I hear that whistle blowin’ I hang my head and I cry

Well I’ll bet there’s rich folks eatin’ in some fancy dining car
Probably drinkin’ coffee and smokin’ big cigars
Well I know I had it comin’ I know I can’t be free
But those people keep a movin’ that’s what tortures me

Well if they freed me from this prison if that railroad train was mine
Bet I’d move it on a little farther down the line
Far from Folsom Prison that’s where I long to stay
Then I’d let that lonesome whistle blow my blues away

Source  https://www.azlyrics.com/lyrics/johnnycash/folsomprisonblues.html

On Saturday we met our friend Paul for lunch in Folsom, California. After a Mexican lunch, we decided to tour the Folsom Prison Museum. When I googled the lyrics for Johnny Cash’s famous Folsom Prison Blues, the analogy to ALS struck me. “But those people keep moving and that’s what tortures me.” For ALS patients their own bodies become prisons while their minds keep working. Sort of like prisoners. The museum had a large section of crafts made by the prisoners – they had time and their minds still worked. This large Ferris Wheel made of toothpicks took a long time to build. 

Well if they freed me from this prison if that railroad train was mine
Bet I’d move it on a little farther down the line
Far from Folsom Prison that’s where I long to stay
Then I’d let that lonesome whistle blow my blues away

For ALS patients, to be freed from our ALS prisons we would gladly hop on that train and let that lonesome whistle blow our blues away.

The old railroad gate with a historic guard house behind
Some prisoners managed to escape from Folsom Prison. For ALS prisoners, those that escape either die or they were misdiagnosed. But we are all hoping and working toward a cure

Those of you who know Paul and Stan and know how their minds work together will see the humourous mild irony in this picture of them in front of Folsom Prison.

Like the prisoners enjoying Johnny Cash’s concerts, ALS patients can continue to enjoy music too, because hearing is not affected. On Tuesday we enjoyed Andy’s Reno Philharmonic Youth Orchestra concert with my dad and Anita and Stan’s cousin Lisa. It was amazing to hear the quality of sound coming from the students in the three orchestras. The students range in age from 7th to 12th grade. Andy’s orchestra even had ballet dancers for Aaron Copeland’s Rodeo which was written as a ballet.

Andy is second chair viola, right in front of the conductor

On Friday I had my salivary gland Botox injections and my ALS clinic appointment at UCSF. My takeaways:

  • Botox – we had a long talk with the doctor about my mucous problem and drooling when the Botox wears off and he adjusted the dose and made my next appointment in ten weeks instead of twelve 
  • Nutrition – I am maintaining steady weight which is good. It was recommended that I add Senna once a day to try to regulate my bowels.
  • Neurologist – she verified my slow progression and referred me to an Ear, Throat, and Nose Specialist for my allergies.
  • Speech – I told her that I never want to be unable to communicate. She gave me a low tech letter board like the one my mom had but this one has a laser pointer that can clip to glasses or a visor and it has commonly used words on it. My mom’s only had letters and we had to point to each letter until she nodded. I now realize how much mom had to say but she could not. I remember when she wanted to tell me something and she spelled out I love you. I have enough trouble saying all I want with my electronic text to speech.
  • Social Worker – we discussed upcoming travel and she facilitated a letter for the airlines and TSA so I can carry my medical equipment on the plane with me. I had all of my equipment with me so the letter contains all the serial numbers.
  • Respiratory – we did not attempt the forced vital capacity or other normal measurements because of my vocal chord involvement in my breathing. But she did measure my normal breathing CO2 output because I have been a little more breathless doing housework, and ordered overnight pulse oximeter study, and increased my Bipap pressures because I somtimes wake up with headaches.
  • Research Project – we had participated in a blood draw research study at the last clinic visit where I was the patient and Stan was the control. This time we each had to fill out a questionnaire. 
  • Blood work – it was nice to be able to go downstairs and get it done 

We are blessed to have a wonderful relative to stay with – Stan’s dad’s cousin Julie. We love her and she lives close to UCSF.

Thanks for another great visit Julie!

I am on the slow train to the ALS prison. I don’t know why my progression is slow. But I am a patient fellow for the ALS/MND International Symposium in Boston starting Friday and I will represent all ALS patients. Please send me your questions and comments for researchers and I will try to get answers. You can comment on this blog or on Facebook or on Twitter.

I will not write a blog next Monday. But I plan two Boston blogs: one from the patient fellow perspective and one from the visiting family perspective. I will be visiting my aunt and uncle the first night and my godmother the last two nights including a lunch with my mom’s cousin, with the conference in between.

Thanksgiving in the U.S. – what I am thankful for

Last Thursday, November 23, was Thanksgiving in the U.S. It is a traditional four day weekend but our local school district added the day before a few years ago, so now it’s a five day weekend. 

We drove to my sister Beth’s in California on Wednesday. She lives south of San Jose, in San Martin. My dad and stepmother, Anita, also drove from Reno. Beth and her husband Jamie have a beautiful home overlooking the CordeValle golf course and a vineyard. Jamie’s sons Phillip and Jack were there too. Because of not quite enough beds, Stan and I stayed at the golf club.

The view from our room.

We had a lovely Thanksgiving dinner at the club.

The beautiful menu – the food was equally beautiful. Jamie’s last name should have a capital B. That is the opposite problem from ours – the small d Macdonalds.

My dad, Phillip, Jamie, Jack, Beth, me, Stan, Andy, and Anita

Although I could not eat the turkey or any of the other wonderful food, I got into the turkey day spirit by drawing a turkey on my feeding tube. Thank you Laura Furumoto for the idea!

We went around the table and each said one thing we are thankful for. Among the comments: indoor plumbing, antibiotics, the first amendment, and the family we were sharing dinner with. Although it is hard to prioritize what I am thankful for, I said I am thankful to still be able self care after nearly two years with ALS. That is not just selfish because it impacts my son and husband greatly. I also seconded the comments about being thankful for everyone at that table. In addition, I am thankful for all of our relatives who we were not with on Thanksgiving.

I am thankful for my friends. Erika and her daughter Maddie came up from Eldorado Hills and spent Friday night and part of Saturday with us. Andy had to sell Christmas trees at his Boy Scout lot at Shoppers Square. Erika bought a tree and I bought a wreath. We will be with Stan’s dad and stepmother for Christmas so we don’t need a tree.

Marvelous Maddie with our wreath
Erika and Maddie with the tree on top of their car to drive over Donner Summit, with Andy and Cooper, who sold her the tree.

Erika even hung the wreath for me.

There are so many friends I am thankful for: the ones from my elementary school, the ones from high school, the ones from college and grad school, and all the friends I have met since I moved to Reno, and also the ones I met online that have become flesh and blood friends.

I am thankful for Radicava and the hope it brings for slower progression of my disease. I am thankful for all the researchers around the world who are working for an end to ALS. I am thankful for all the people who work in ALS clinics to help ALS patients have better quality of life. I am thankful for all the wonderful people with ALS and the wonderful caregivers I have met through ALS fundraisers, Facebook, and our local support group. I am thankful for the people who facilitate our support group.

I am thankful to be a patient fellow for the ALS/MND International Symposium in Boston December 8th through December 10th. I again encourage anyone with questions or comments about anything related to ALS/MND that you want the researchers to hear, please send me your questions and comments. I will be your voice at the conference. Again, you can comment on this blog or on Facebook or on Twitter.

I am also thankful for a fun Twitter interaction. The father of neurology is Jean-Martin Charcot, a brilliant doctor in the late 1800’s in France who first identified and classified ALS, MS and other neurological diseases. Well, Jean-Martin Charcot is on Twitter and he shared my blog! I could not agree more!

My Aim is to Represent 

I am honored to announce that I have been chosen to be a Patient Fellow for the 28th International Symposium on ALS/MND in Boston in December. The other fellows are an auspicious group that I am looking forward to meet and work with. You can read all about us here: https://alsmndpatientfellows.wordpress.com We were chosen to represent all ALS/MND patients (ALS is called Motor Neuron Disease in many parts of the world).

The selection committee is also impressive. You can read about them at that link too.

We (patient fellows and committee) will be working to get ready for the conference by picking the sessions we will attend and planning how we will share what we learn. This is a new program to have researchers have more interaction with patients and have patient input into the research directions. I look forward to sharing exciting new research through this blog.

I will be able to provide updates as the conference approaches. An added bonus for Stan and me is we can visit relatives – my Uncle Bill and Aunt Candy before the conference and my godmother Aunt Alice for a couple of days after. I also hope to see my mom’s cousin Len, who helped me with the family history for the UCSF study.

This week I got an appointment for my surgery for installation of a port for the new drug Radicava. It will be Tuesday October 10th. We had our monthly ALS Association support group meeting and Nurse Educator Meg gave a presentation on Radicava, the first new drug for ALS in 20 years.

She told me that Option Care, who will provide the drug, is now researching exactly what my insurance company will cover, and she thinks they should be ready for me to start the new treatment right after I get the port. Of course I would start earlier by IV if I can.
I also got together with dear friends that I worked with 30 years ago, Sunny and Lisa.

We had so much fun reminiscing about all the people we used to work with. We also enjoyed getting caught up with each other and plan to do so monthly.

And again on Friday, Stan missed a call from Option Care at 5:20 P.M. When he called back he got the answering service. So again, I am waiting through a weekend to make more progress. But at least there is still progress to hope for!