"Is it genetic?"
The question we should be asking as a matter of course as we seek a cure
It is the first thing many people ask you when you reveal that you have been diagnosed with Parkinsons’s - “is it genetic?” By which I suppose they mean did you get it from a parent. Now as my father had Parkinson’s that was relevant but at first I had no way of knowing for sure. A genetic test is not a routine part of the diagnostic process, even though something like 15% of Parkies have one of the mutated genes linked to the disease.
But a couple of years ago, after a discussion with my neurologist at our annual appointment, he did send me off for a gene test. After many months the result came back - I did not have a gene mutation, Like most people with Parkinson’s, mine was idiopathic - in other words there was no clue where it came from.
But while the test did not make anthing much clearer - except that I could not blame my dear old dad for my Parkinson’s - I am glad I had it. Because after a conversation with the co-founder of a company called Sano Genetics I am convinced that genetic testing is going to play a far bigger role in the hunt for cures for Parkinson’s and many other conditions.
Patrick Short is an American geneticist who came to the UK to do his PhD at Cambridge’s Sanger Institute and stayed to found Sano. His doctorate looked at potential genetic causes of developmental disorders in children but he told me he also had a very personal reason for his interest in the field: “My family has a rare genetic kidney disease. So my dad's had a transplant, his brother has had two, their father and uncle had transplants.”
As he went through genetic testing himself he started thinking about how laborious the whole process was:
“One of the gaps for researchers is still how time consuming and hard it is to run genetic studies. We know that we need them in basically every therapy area that there is, from newborns to adults to everything in between.”
The idea behind Sano Genetics was to smooth the path through genetic testing for both researchers and clinical trial participants: “For participants, we make it easier for them to get access to a genetic test that could help them make a decision about new therapies or family planning…. For researchers, we make it easier for them to run a genetic study in order to accelerate the development of their precision medicine therapeutics.”
Started in 2018, the company now has 70 employees and works with drug companies and academic researchers to organise the genetic testing often needed to recruit participants in drug trials. One area where they are involved is Parkinson’s, where two genes GBA and LRRK2 are of particular interest to researchers.
“There's a little bit of a catch 22 - there are lots of precision medicines being developed that target LRRK2 and GBA and other genetic forms of the disease, but in almost every country, the vast majority of patients don't get access to genetic testing.”
Easy access to genetic testing is obviously important for speeding up the tortuously slow process of recruiting participants into clinical trials. But Patrick Short sees other reasons for having a greater percentage of the population tested. One would be to get early warning of your likelihood of getting something like Parkinson’s. But what useful purpose would be served by telling a 20 year old for instance that they had the LRRK2 gene mutation so making it more likely that they would get the degenerative brain disease?
“It's not a foregone conclusion that if you're 20 years old today and you have the gene, you will definitely go on to get it,” says Patrick. “We've got 30 years of time to do prevention research.” He was tested and found he had the same gene which caused his father to need a kidney transplant but he has been working with clinicians looking at early detection and potentially prevention of this very rare kidney disease about which very little is known.
For Parkinson’s there is already far more data available - the UK Biobank project has been tracking the general health of half a million people for more than a decade and during that period it is certain that a number of participants will have developed Parkinson’s. It is by tracking people very early in the development of the disease that researchers are pinning their hopes of a cure for either the genetic or idiopathic version.
Almost all cases of Parkinson’s were described as idiopathic 30 years ago, but as new discoveries are made about genes linked to the disease, the proportion labelled genetic has grown.
Patrick Short says knowing about the genetics of a disease from early on presents his company and others like it with a great opportunity: “Can we go five years earlier than disease onset and start to treat it then, and instead of slowing progression or halting progression, can we just stop it from happening in the first place?”
It is a bold vision. The genetic revolution has come a long way in the 21st century but finding a cure for a complex condition. like Parkinson’s where we are still unclear about the causes will be a huge challenge. Still, how refreshing to hear such ambition - now let’s make genetic testing after diagnosis the norm and give the geneticists access to that data so they can pursue that vision.
My brother, 63 has it (been diagnosed about 2 years) and my mother had it for around 20+ years before she died at 91 in 2019. So I have an ongoing interest. No idea if my brother inherited the gene. He once asked me pointedly if I was worried. I said that I'd been told it was not hereditary. So I am interested that there is a link for some, at least a gene that could lead to Parkinson's. It still begs the question as to what tips an individual over to actual Parkinson's.
Is anyone doing further work on the effect of pesticides or other pollutants and poisons that were used a lot when we were growing up? In other words other substances that cross the blood brain barrier or similar. It worries me that some cancers have been associated with pesticides or types of plastics, such as certain types of breast implant. Maybe certain neurological diseases are also affected and we just don't know the damage that's been done or is being done by our contaminated environment.
Yes, I think all YOPD should be genetically tested, I was diagnosed with Parkinson’s in 2012 at the age of 45, I subsequently volunteered as part of the 1000 gnome project and results came back that I inherited HSP type 7 , im still taking my Parkinson’s medication (sinemet & madopar plus a rotigotin patch) and I’m due to see a HSP specialist in Cambridge.