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:
- An ageing population and more people being diagnosed with Parkinson’s every year
- 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
- Over the next 10 years, the approval of some drugs that slow progression of the disease for some people
- 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
- 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 |
