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This week the outcome of an ongoing Parkinson’s clinical trial was announced.
Data collected during Part 1 of the ongoing Phase 2 PASADENA alpha synuclein immunotherapy study for Parkinson’s apparently suggests that the treatment – called prasinezumab – has not achieved it’s primary endpoint (the pre-determined measure of whether the agent has an effect in slowing Parkinson’s progression – in this case the UPDRS clinical rating scale).
But, intriguingly, the announcement did suggest ‘signals of efficacy‘ in secondary and exploratory measures.
In today’s post, we will discuss what immunotherapy is, what we know about the PASADENA study, and why no one should be over reacting to this announcement.
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At 7am on Wednesday, April 22nd, 2020, the pharmaceutical company Roche published its sales results for the 1st Quarter. This was just prior to the opening of the Swiss Stock Exchange. The financial report looked very good, particularly considering the current COVID-19 economic climate.
There was, however, one sentence on page 133 of the results that grabbed some attention:
For those of you (like myself) who struggle with fine print, the sentence reads:
“Study did not meet its primary objective, but showed signals of efficacy“
This was how the pharmaceutical giant announced the top line result of the ongoing Phase II PASADENA study evaluating the immunotherapy treatment prasinezumab in recently diagnosed individuals with Parkinson’s (listed on the Clinicaltrials.gov as NCT03100149).
At the time of publishing this SoPD post, Roche are yet to provide any further information (press release, announcement, memo, tweet, etc) regarding the results of the study.
Thankfully, a smaller biotech firm called Prothena – which is also involved in the development of the agent being tested in the Pasadena study – has kindly provided a few more details regarding these results.
In today’s post we will discuss what details have been shared in the Prothena press release regarding the Prasinezumab clinical trial in Parkinson’s (Click here to read the press release).
What is Prasinezumab?
Recent regulator approvals and exciting new preclinical data has refocused attention on a treatment approach for genetic conditions that has travelled a long and winding road towards clinical use.
Antisense oligonucleotides represent a method of altering protein levels at the post transcriptional level – it basically stops certain RNAs from being translated into protein.
And recently, a new clinical trial has been registered which will explore the use of this treatment approach in people with Parkinson’s.
In today’s post, we will look at what antisense oligonucleotides are, how they work, what research has been conducted in the context of Parkinson’s, and some of the limitations of this approach that still exist.
Spinal muscular atrophy (or SMA) is a genetic disorder that results in the degeneration of motor neurons in the spinal cord. This leads to progressive weakening and atrophy of muscules, ultimately leaving sufferers paralysed. It is caused by loss-of-function mutations in the survival motor neuron 1 (SMN1) gene.
It is a terrible condition that starts in very young children and has an incidence approaching 1:10,000 live births.
Luckily, novel therapies are being developed to deal with this condition, and in 2016, the US FDA approved a new treatment – following rather dramatic clinical trial results – called Nusinersen. This new therapy has caused a great deal of excitement as it basically halted the progression of SMA in many cases.
And a recent long term report highlights some of these very impressive results:
Title: Nusinersen in later-onset spinal muscular atrophy: Long-term results from the phase 1/2 studies.
Authors: Darras BT, Chiriboga CA, Iannaccone ST, Swoboda KJ, Montes J, Mignon L, Xia S, Bennett CF, Bishop KM, Shefner JM, Green AM, Sun P, Bhan I, Gheuens S, Schneider E, Farwell W, De Vivo DC; ISIS-396443-CS2/ISIS-396443-CS12 Study Groups.
Journal: Neurology. 2019 May 21;92(21):e2492-e2506.
PMID: 31019106 (This report is OPEN ACCESS if you would like to read it)
Most importantly, Nusinersen is having real impact on the children who are affected by this condition:
Interesting, but what exactly is Nusinersen?
It is an antisense oligonucleotide.
What are antisense oligonucleotides?
On the 26-31st March, the 14th International Conference on Alzheimer’s and Parkinson’s Diseases (or ADPD meeting) was held in Lisbon, Portugal.
For 5 days – between 8:30am and 7:30pm each day – over 4000 researchers were able to attend lectures of new results and ideas, in any of 8 different auditoriums. Alternatively, they could wander among hundreds of research posters.
It was a marathon effort, however, for all attendees. And a great deal of new results were shared.
In today’s post, we will discussed what was presented at the 2019 ADPD meeting and what was actually learnt.
Lisbon. Source: stmed
Lisbon is a city, midway down the western coast of the Iberian Peninsula.
It is home to a little over 500,000 people (3 million in the wider metropolitan area), and it serves as the capital city for the Portuguese people.
The Castelo de Sao Jorge, rises above Lisbon. Source: Wikipedia
Interestingly, it is the 2nd oldest European capital city (after Athens), and has had a rich and fascinating history given its strategic location. But on the 1st November 1755, 20% of the population were killed and 85% of the city’s structures were destroyed by a terrible earthquake and subsequent tsunami, which resulted in the vast majority of the city being rebuilt.
The ‘new city’ is laid out in bairros de Lisboa (neighbourhoods of Lisbon) across a hilly landscape, providing views of the River Tagus at every vantage point. And while walking the steep cobblestoned streets is delightful, there is a system of vintage public trams that can take a lot of the leg work out of the effort.
During the last week of March 2019, Lisbon was the site of the ADPD meeting.
What is the ADPD meeting?