As the amazing Australian Parkinson’s Mission project prepares to kick off, across the creek in my home land of New Zealand, another very interesting clinical trial programme for Parkinson’s is also getting started. The study is being conductetd by a US biotech firm called resTORbio Inc.
The drug being tested in the study is called RTB101.
It is an orally-administered TORC1 inhibitor, and it represents a new class of drug in the battle against Parkinson’s.
In today’s post, we will look at what TORC1 is, how the drug works, the preclinical research supporting the trial, and what this new clinical trial will involve.
Rapa Nui. Source: Chile.Travel
Today’s post kicks off on an amazing south Pacific island… which is not New Zealand.
In 1965, a rather remarkable story began in one of the most remote inhabited places on Earth – the mysterious island of Rapa Nui (or “Easter Island”).
And when we say ‘remote’, we really do mean remote. Did you know, the nearest inhabited island to Rapa Nui is Pitcairn Island, which is 2,075 kilometres (1,289 mi) away. And Santiago (the capital of Chile) is 2,500 miles away – that’s a four-hour+ flight!!!
Rapa Nui is the very definition of remote. It is as remote as remote gets!
Does Amazon deliver to the town of Hanga Roa? Source: Atlasandboots
Anyways, in 1965 a group of researchers arrived at Rapa Nui with the goal of studying the local inhabitants. They wanted to investigate their heredity, environment, and the common diseases that affected them, before the Chilean government built a new airport which would open the island up to the outside world.
It was during this investigation, that one of the researchers – a University of Montreal microbiologist named Georges Nógrády – noticed something rather odd.
At the time of the study, wild horses on Rapa Nui outnumbered humans (and stone statues).
Wild horses roaming the east coast of Rapa Nui. Source: Farflungtravels
But what was odd about that?
Georges discovered that locals had a very low frequency of tetanus – a bacterial infection of the feet often found in places with horses. He found this low incidence of tetanus particularly strange given that the locals spent most of their time wandering around the island barefoot. So Georges decided to divide the island into 67 regions and he took a soil sample from each for analysis.
In all of the vials collected, Nógrády found tetanus spores in just one vial.
Something in the soil on Rapa Nui was extremely anti-fungal.
In 1969, Georges’ collection of soil samples was given to researchers from the pharmaceutical company Wyeth and they went looking for the source of the anti-fungal activity. After several years of hard work, the scientists found a soil bacteria called Streptomyces hygroscopicus which secreted a compound that was named Rapamycin – after the name of the island – and they published this report in 1975:
Title: Rapamycin (AY-22, 989), a new antibiotic
Authors: Vézina C, Kudelski A, Sehgal SN.
Journal: J Antibiot (Tokyo). 1975 Oct;28(10):721-6.
PMID: 1102508 (This report is OPEN ACCESS if you would like to read it)
It is no understatement to say that this was a major moment in biomedical history. So much so that there is actually a plaque on the island commemorating the discovery of rapamycin:
Why was the discovery of ‘anti-fungal’ rapamycin so important?!?
Over the last 12 months, the Silverstein Foundation has quickly established itself as a major focused force in the fight against Parkinson’s.
And when I say ‘focused’, I mean ‘focused’ – the foundation is “actively pursues and invests in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in glucocerebrosidase (GBA) mutation carriers”.
But the output of this effort may well have major benefits for the entire Parkinson’s community.
In today’s post, we will discuss what GBA is, how it functions inside cells, its association with Parkinson’s, and what all of this GBA focused research being funded by the Silverstein Foundation could mean for the Parkinson’s community.
Jonathan Silverstein. Source: Forbes
This is Jonathan Silverstein.
He’s a dude.
He is also a General Partner and a Co-Head of Global Private Equity at OrbiMed – the world’s largest fully dedicated healthcare fund manager. During his time at OrbiMed, the company has invested in healthcare companies that have been involved with over 60 FDA approved products.
In February 2017, he was diagnosed with Parkinson’s disease at just 49 years of age.
Rather than simply accepting this diagnosis, however, Mr Silverstein decided to apply the skills that he has built over a long and successful career in funding biotech technology, and in March 2017, he and his wife, Natalie, set up the Silverstein Foundation.
They raised $6 million from donors and then provided another $10 million of their own money to fund the endeavour, which has funded a dozen research projects and started a new company called Prevail Therapeutics (we’ll come back to this shortly).
The foundation has just one mission: “to actively pursue and invest in cutting edge research with the goal of discovering new therapies for the treatment of Parkinson’s Disease in GBA mutation carriers”
And it seeks to address this by achieving three goals:
- to find a way to halt the progression of Parkinson’s with GBA.
- to identify regenerative approaches to replace the damaged/lost cells
- to find preventative measures
What is ‘GBA’?