Shall we FaceTime?

Wednesday 1 April 2020

“Shall we FaceTime?” I asked.

Rachel sounded surprised at my suggestion. I continued:

“It will be much better if we can see each other. You might even be able to do some clinical tests.”

After some faffing we managed to connect and we both spontaneously did that most human of things: we gave each other big smiles.

“That’s much better, isn’t it?” I concluded.

I had received a letter informing me that my six-monthly neurology appointment would be by phone because of the coronavirus. It had actually been a year since I had seen Rachel as, on my last visit, I had seen The Professor. Rachel is one of his research team, and seemingly the person looking at my family case.

The conversation was friendly enough but routine. I told her that I felt I could stay on the same medication, with the levodopa tablets giving me the flexibility I need with my Parkinson’s: although I am prescribed three tablets a day, I sometimes take just one or two and, at other times take four or even five depending on the ebb and flow of the condition. Rachel said this was fine, and that I should be guided by how I feel.

There was not much news about my genetic analysis. She said they ideally need DNA samples from more family members to help isolate the faulty gene(s). My mother (who has Parkinson’s) and her brother (who doesn’t have Parkinson’s) have both given samples, but I now need to encourage my sister (two years younger, no signs yet of Parkinson’s) to donate her DNA to medical science as well.

After a convivial half hour, we concluded with some basic clinical tests, primarily some simple finger tapping, which were actually quite effective over the phone camera. I will see her again in September. Perhaps in person, but I suspect by FaceTime again.

It’s surprising how we have all adjusted so quickly to the new normal of living in isolation and communicating via video links.  Like millions of other people, I now have a mini office set up at home and spend a good chunk of my working day talking to other people on a screen.

I’m really very fortunate: I still have a good job, I get to sit in the comfort of my own home all day, eat and drink well, exercise, and I am able take a rest whenever I need it. Clara and I are “staying safe”.

I find myself thinking about the million people across the world who now have a confirmed diagnosis of covid-19. They are also doing most of their communication via a screen and video camera.

Sadly, some of them won’t ever get to see their loved ones in the flesh again.

Flying first class

Thursday 13 February 2020

Today I am flying Emirates first class from Dubai to London.

It’s awesome. Some say it’s the best first class in the world but I wouldn’t know about that. This is probably the only time in my life I will fly first class on an airline like this.

The experience starts with the chauffeur whisking me smoothly to the airport in his S-class Merc. He drops me off at the separate check-in section without any queues at security, naturally.

I head to the first class lounge, a vast oasis of calm in an otherwise heaving airport, where the staff outnumber the passengers. I elect to have a la carte fine dining: delicious sashimi to start, veal saltimbocca for main, and a fruit and cheese plate to round it off. As expected, the wine is also excellent. I don’t bother with the spa or cigar room, but I do use the sleep area for a while after a glass of 15-year-old Glenfiddich.

Once on board, the beaming stewardess hands me a hefty goodie bag. Bulgari amenities, gourmet snacks galore, pyjamas for the overnight journey, slippers, moleskin notebook and pen.  She offers me a pre-take off drink. I don’t hesitate in my choice: a glass of Dom Perignon 2008 Champagne.

There’s a fresh orchid in my compartment. Enough gadgets for a James Bond movie and more bling than, well, an Emirati 5-star hotel room.  A screen as big as my TV at home, and so the list goes on.

How did I get here?

I’ve done a few business trips to the Middle East and saved up some miles. It turns out that that the Emirates loyalty scheme is not very generous. Surprisingly, BA’s Avios are much better for getting reward flights.

With my working days numbered, and business travel becoming increasingly exhausting, it made sense to use my Emirates points for an upgrade, rather than wait for a reward flight that will likely never come.

So I’m making the most of the absurd luxury while I still can. Things will start changing soon. I will need to cut back further at work, stop the travel, and retire in two or three years with a pension pot that will very much put me at the back of the plane, if indeed I’m on the plane at all.

We will be landing soon. Whilst I enjoy my scrambled eggs and cup of tea, I reflect on the best bit of my journey. 

Taking a morning shower at 41,000 feet. Obviously.

Hope fatigue: will there ever be a cure?

Saturday 1 February 2020

At the start of 2020 there was a flurry of posts on various Parkinson’s forums about all the promising research and clinical trials in progress, not to mention a few puns around “20/20 vision”.

Rather than repeat it all here (and probably get some of it wrong), I would refer you instead to The Science of Parkinson’s take on the topic, The Road Ahead: 2020. It’s a long article so I’ve attempted to summarise the drug trials referenced at the bottom of this post.

Wow. There are a lot of candidate treatments currently being tested, and many threads of more fundamental research also in progress. But we’ve been down this road before.

One thing that Dr Simon Stott alludes to in his post is the idea of “hope fatigue”. Despite the long list of therapies currently in clinical trials, the sobering reality is that the underlying cause of Parkinson’s is not understood, the different types of Parkinson’s are not fully identified or understood and there have been no significant new drugs since the discovery of levodopa and the dopamine agonists in the 1960s. In the last 50 years or so, there have been numerous headlines about promising new medicines that have all come, essentially, to nothing. For long sufferers of the disease, hope fatigue is a very real phenomenon.

Of course, eventually there will be a cure, or at least treatments to improve life with the disease. The human race is too smart, and the collective effort being put into neurodegenerative diseases too great, for us not to figure something out.

The real question is when? Will there be a cure, for example, in my lifetime?

Crystal ball gazing is a hazardous pursuit, but let’s see what the data tells us.

Firstly, let’s look at the amount of Parkinson’s research. A count of research papers on PubMed with the tag “Parkinson’s” reveals that the number of papers published has quadrupled over the last twenty years.

Compared to other neurological conditions, Parkinson’s doesn’t do too badly in terms of the amount of research published. But it is dwarfed by research into conditions like diabetes and the work across different types of cancer or even HIV.

What about funding for research? We would expect this to be correlated with the number of papers published.

After gradual reductions in real terms over recent years of the amount that governments in, for example the UK and the US, have been setting aside for research across all the medical sciences, is on the increase. For example, the United States Congress recently passed its budget for Fiscal Year 2020 which included a $2.6 billion increase for the National Institutes of Health (NIH), bringing the agency’s budget up to $41.46 billion.

However, Parkinson’s only gets a tiny slice of the government research funding pie. More significant is private funding for research. The biggest source for this is the Michael J Fox Foundation. Their annual contribution to Parkinson’s research has increased by 42% over the five years since 2014 (watch out for the slightly misleading scale on the graph). This increase in funding is consistent with the increase in the amount of research output that we saw earlier.

In summary, the amount of research into Parkinson’s is high compared to other neurological conditions and has been consistently growing over recent years, but it is still small compared to many other medical conditions.

Does it deserve more funding? Given the number of people affected, maybe. But in the majority of cases, people can still have a reasonable life for quite a few years with Parkinson’s and it’s a very different story for most types of cancer for example. Or Alzheimer’s for that matter.

What can we learn from other conditions?

AIDS/HIV is essentially resolved from a medical perspective though the antiretroviral drugs used to treat it remain too expensive for many. The total global spend between 2000 and 2015 on the disease was an astonishing $562 billion according to the Institute for Health Metrics and Evaluation (IHME) at the University of Washington. Yes, that’s half a trillion dollars. More than the annual GDP of Thailand with its population of 70 million.

Similarly, research spending on cancer, which has made great progress in the last couple of decades, runs into tens of billions of dollars per year.

The lesson is clear: finding cures for tricky medical conditions requires a lot of funding, way more than Parkinson’s or Alzheimer’s currently receive. We’ll get there in the end but at current levels of investment it will take time.

So, as I gaze very speculatively into my crystal ball, what I see is:

1. An ageing population and more people being diagnosed with Parkinson’s every year
2. Steadily increasing research funding from governments and private organisations, and a corresponding increase in research output, but at an absolute level lower than many other conditions
3. Over the next 10 years, the approval of some drugs that slow progression of the disease for some people
4. Over 10-20 years, an understanding of the underlying cause(s) of some variants, and perhaps treatments that can restore missing neurons, thereby reversing the disease
5. Over 20-40 years, science starts winning the war, systematically understanding the different variations of Parkinson’s, developing reliable screening for risk factors, and finally finding a cure (or set of cures)

Where does that leave hope?

Given these assumptions, I don’t follow every research thread or get excited at every news headline. But it’s not really a case of hope fatigue. For myself I don’t expect to be cured (and would be pleasantly surprised if this did happen). But I have every hope – indeed expectation – that the next generation won’t have to suffer from the disease that James Parkinson first described 203 years ago.



Table of current trials

Target	Drug under development or in clinical trials	Companies/ parties involved
Alpha synuclein immunotherapy (attacking the build up of alpha synuclein using either the brain’s own antibodies or artificial ones)	Prasinezumab	Roche, Prothena Biosciences
	BIIB054	Biogen, SPARC
	MEDI131	AstraZeneca
	Lu AF82422	Lundbeck, Genmab
	BAN0805/ABBV-0805	AbbVie, BioArctic Neuroscience
	AFFITOPE PD01A	AFFiRiS
	UB-312	United Neuroscience
	NPT088	Proclara Biosciences
	NPT520-34	NeuroPore Therapies
	NPT200-11	UCB
	ENT-01	Enterin
	YTX-7739	Yumanity
	Mannitol	Clinicrowd
	Anle138b	MODAG
LRRK2 inhibitors (for people with a PD-inducing mutation in the LRRK2 gene)	DNL-201	Denali Therapeutics
	BIIB094	Biogen, Ionis Pharmaceuticals
PINK1 and PARKIN inhibitors	TBA	Mitokinin
	TBA	Vincere
	iCP-Parkin	Cellivery
GBA therapies	Ambroxol	Cure Parkinson’s Trust, Van Andel Institute
	Venglustat	Sanofi Genzyme
	LTI-291	Lysosomal Therapeutics
	TBA	Prevail Therapeutics
	AVR-RD-02	AVROBIO
	ESB1609	E-scape Bio
	S-181	Surmount Bio
c-Abi and TORC1 inhibitors (boosting the body’s natural autophagy mechanism)	Nilotinib	Georgetown University
	K0706	SPARC
	FB-101	1ST Biotherapeutics, Neuraly
	Radotinib	Il-Yang Pharmaceutical
	IkT-148009	Inhibikase Therapeutic
	RTB101	resTORbio
NLRP3 inhibitors and other anti-inflammatories	Inzomelid	Inflazome
	NT-0167	NodThera
	Azathioprine	Cambridge University
	XPro1595	INmune Bio
	Sargramostim	Parkinson’s Nebraska
GLP-1R agonists (protecting further neurons from dying)	Exenatide
	Lixisenatide
	Liraglutide
	Semaglutide	Novo Nordisk
	NLY01	Neuraly
	PT320	Peptron
Neurotrophic factors (growth hormones for neurons)	GDNF	Cure Parkinson’s Trust, Brain Neurotherapy Bio, Genecode
	CDNF	Herantis
Mitochondria boosters	UDCA	University of Minnesota
	CNM-Au8	Clene Nonomedicine
	Terazosin
	EPI-589	BioElectron
	CuATSM	Collaborative Medicinal Development
	Nicotinamide Riboside
	AMX0035	Amylyx
Statins (for neuroprotection)	Lovastatin
	Simvastatin	PD-STAT
Iron reduction	Defeiprone	Apopharm
	PBT434	Alterity Therapeutics
Plasma infusion	GRF6021	Alkahest
Other neuroprotection	Lingzhi
	Ceftriaxone
	KM-819	Kainos Medicine
	DA-9085	Dong-A ST
	ANAVEX2-73	Anavex
Cell transplantation	N/A	Transeuro
	N/A	International Stem Cell Corporation
	N/A	Center for iPS Cell Research and Application
	N/A	BlueRock Therapeutics
	N/A	Aspen Neuroscience