Is a vaccine for Parkinson’s disease possible?

Finding a truly effective treatment for Parkinson’s disease – which goes beyond simply managing symptoms – has long been a challenging task and, to date, none of the available therapeutic options exist that can effectively slow or stop the underlying disease. However, research and trials to find a treatment are ongoing and, because World Parkinson’s Day falls on April 11, we are exploring whether developing a vaccine for Parkinson’s could be a viable option to prevent the disease from developing.

The first detailed medical description of Parkinson’s was published in 1817, in an essay entitled ‘An Essay on the Shaking Palsy’, written by the English physician James Parkinson – after whom the disease is named. This essay helped establish Parkinson’s as a recognized medical condition.

Fast forward six decades to the mid-1800s, and it is Jean Martin Charcot – the French neurologist – who refined and expanded on James’ earlier description of Parkinson’s disease by describing the clinical spectrum of Parkinson’s, and separating it from multiple sclerosis (MS) and other disorders characterized by tremors.

Now, after more than two centuries of research, we know Parkinson’s is a neurodegenerative disease caused by the death and dysfunction of neurons in a part of the brain called the substantia nigra, which leads to a reduction in dopamine – the chemical that coordinates movement. Because of this reduction, the disorder causes motor symptoms, such as tremors, slowness, stiffness, and problems with balance and walking.

Although ‘treatments’ for Parkinson’s first appeared in the early 19th century – based on empirical observations and anticholinergic drugs – the first effective treatment of Parkinson’s symptoms came in the 1960s after the discovery of the dopaminergic deficit in the disease. This led to the development of Levodopa, which works by being converted to dopamine in the brain, and is still the most widely used drug for Parkinson’s today.

However, despite its widespread use, there is no getting away from the fact that Levodopa only treats the symptoms of Parkinson’s rather than slowing or stopping the progression of the disease. Given that more than 10 million people are living with Parkinson’s worldwide, there is an unmet need for more preventive treatment options.

With this in mind, along with the development of small molecule treatments and monoclonal antibodies, researchers and biotechnologists are also exploring the possibility of creating a Parkinson’s vaccine that would prevent the development of the disease.

What does a vaccine for Parkinson’s require?

Parkinson’s is associated with protein deposits in the brain called Lewy bodies, which consist of accumulations of alpha-synuclein. In Parkinson’s, the alpha-synuclein misfolds and coalesces into Lewy Bodies. Therefore, it is thought that preventing alpha-synuclein aggregation and removing existing clots could be an effective way to treat Parkinson’s.

“In order to develop a therapy, you really need to have technology that specifically – or as specifically as possible – targets the Parkinson’s protein, namely alpha-synuclein, and targets this pathologically misfolded form of alpha-synuclein,” explains Andrea Pfeifer, co-founder and chief executive officer (CEO) of AC Immune, which is currently developing an investigative vaccine for Parkinson’s.

The current approach to the Parkinson’s vaccine is the introduction of a molecule that induces the body to produce its own antibodies against alpha-synuclein, leading to active immunity. In doing this, the idea is that the antibody will bind to the clumping alpha-synuclein and help break it down.

One of the particular benefits of creating a vaccine for Parkinson’s comes in the form of efficiency and cost-effectiveness. As Mei Mei Hu, CEO of Vaxxinity points out, “as a drug delivery modality, vaccines are easy to consume, easy to manufacture, and cheap to manufacture.”

Pfeifer also agrees with this sentiment and says that AC Immune hopes to get away with giving only one or two vaccinations per year with its vaccine candidate, which is important not only from a cost standpoint, but also from a convenience standpoint.

Vaccines in clinical development show promise

There are currently two important vaccines in clinical development that utilize active immunity that have shown promising results from phase 1 trials.

AC Immune is working on the development of one of these vaccines, known as ACI-7104. This comes after acquiring the Affiris therapy portfolio targeting alpha-synuclein, including Affitope PD01A, which is Affiris’ clinically validated active vaccine candidate for the treatment of Parkinson’s. A phase 1 trial of PD01A demonstrated its long-term safety, efficacy and tolerability.

“We started with a clinically validated product candidate, which we are now taking to phase 2. We repeated some of the research because when you get a product it is very important that you have complete trust and your foundations are clear. So, we looped through a lot of data and it was very, very good, and we manufactured the product, we went to different countries for regulatory approvals and we got it all,” Pfeifer said.

According to Pfeifer, it’s only a matter of time before the company announces its first patient dose and, if all goes according to plan, they hope to have the first immunogenicity data by the end of the year.

Another investigative vaccine with promising results so far from phase 1 trials is UB-312, which is being developed by Vaxxinity. Again targeting the toxic form of alpha-synuclein aggregates in the brain, it is intended to treat Parkinson’s and other synucleinopathies, such as dementia with Lewy bodies (DLB) and multiple system atrophy (MSA).

Part A of the phase 1 trial has been completed and demonstrated that UB-312 is well tolerated and immunogenic in healthy volunteers, with a higher response rate and antibodies that cross the blood-brain barrier. Meanwhile, phase 1 part B trials are currently underway, but have shown some positive results.

“We saw that UB-312 is also well tolerated and immunogenic in Parkinson’s patients, based on an end-of-treatment analysis of the ongoing Phase 1 Part B trial. We hope to complete this trial by mid-2023,” said Hu.

Vaxxinity uses the Vaxxine Platform to activate the immune system and stimulate antibody production. This technology specifically utilizes synthetic peptides to optimally mimic and combine biological epitopes.

The challenge of developing a vaccine for Parkinson’s

Although a vaccine may be an accessible, affordable, and effective treatment for Parkinson’s, developing it presents a number of challenges.

“Designing clinical trials in Parkinson’s disease presents many challenges. First, neurodegeneration progresses for many years before diagnosis, so identifying patients at an early stage of the disease is important. Vaccines may eventually be suitable for the prevention of neurodegeneration, but we still lack diagnostic biomarkers that would help identify patients in the early stages of the disease (that is, before symptoms appear),” said Hu.

“In addition, symptoms are generally slow-developing and heterogeneous, meaning that assessing the beneficial effects of the drugs under study needs to be done over a long period of time and in large patient populations.”

Pfeifer also cited diagnostics as being a challenge in the development of a Parkinson’s vaccine, and said that diseases like MSA, which is a subtype of Parkinson’s, have a relatively high rate of misdiagnosis, which is one of the reasons it is so difficult to get it. successful clinical trials.

“We don’t yet have the tools to properly diagnose people to include the right patients in clinical trials, and then clearly track the impact of the treatment,” said Pfeifer.

At AC Immune, they try to address this issue by monitoring the development of diagnostic and therapeutic candidates, so they can ensure they are selecting the right patient for the right disease.

Meanwhile, dr. Arthur Roach, director of Parkinson’s Virtual Biotech, said that the lack of understanding of how alpha-synuclein works means there is still a long way to go before we see a Parkinson’s vaccine.

“The reality is that right now, we still need to learn and understand about alpha-synuclein and its behavior in the brain in order to properly target it in efforts to deliver a Parkinson’s vaccine,” Roach said. .

“This is not to say that there cannot be a vaccine, but based on current evidence, it will likely take decades to hone and produce. We are starting to see progress in potential cancer vaccines where molecular targets have been identified, but in a neurological condition like Parkinson’s our understanding may be 10-15 years behind that.”

While a Parkinson’s vaccine might one day – especially given the promising early results from recent trials of ACI-7104 AC Immune and UB-312 Vaxxinity – it’s hard to say whether we’ll see successful development of an effective vaccine any time soon.

However, there is reason to hope that a cure for the disorder may be within reach, with various investigative treatments currently being developed for it.

“Therapeutic pathways currently being developed for Parkinson’s are powerful and diverse; the scientific research community continues to show an ardent interest in reducing the impact of debilitating diseases… Excitingly, drugs under research aimed at halting or slowing the process of neurodegeneration have advanced to late-stage clinical trials, and may become available before the end of the decade, assuming that efficacy and safety are confirmed,” said Hu.

New technologies related to Parkinson’s disease:

Source link

Related Articles

Back to top button