CDx | Neurogenerative Disease

Precision medicine for a neurological disease that can affect anyone

 
Neuron23 is on a mission to develop a disease-modifying drug for Parkinson’s disease. With the help of companion diagnostics, the biotech startup wants to identify patients who are likely to benefit from precision medicines. The approach promises to radically alter the progress of devastating neurodegenerative diseases that can affect everyone.

When Nancy Stagliano was getting her PhD in neuroscience at the University of Miami Miller School of Medicine, she watched her father’s rapid decline, and eventual death, from the rare and fatal degenerative neurological disorder progressive supranuclear palsy (PSP). “It was a very difficult two years with a rapidly progressing disease,” says Stagliano. 

“It was a powerful moment when I realized how quickly a neurodegenerative disease can progress.” She adds that the disease behaved a lot like an aggressive cancer and less like many neurodegenerative disorders with symptoms that progress over 20 or 30 years.

Her father’s precipitous decline intersected with her research interest and drove Stagliano to eventually enter the field of neurodegenerative diseases. Today, more than 20 years later, the neuroscientist and serial biotechnology entrepreneur is working at the cutting edge of developing therapeutics for devastating neurological diseases. 

In 2018, Neuron23 was founded and Stagliano joined as Executive Chair of the Board before becoming CEO in late 2019. Neuron23 is a venture-backed biotechnology clinical-stage startup in South San Francisco that uses advanced techniques in artificial intelligence (AI) and data science to create precision-medicine treatments that target neurodegenerative and neuroinflammatory diseases in patients with specific gene mutations.

There are many examples of precision medicine in oncology but none in neurological diseases – yet. The hope is that a more precise approach, relying on companion diagnostics to identify patients who are most likely to respond to therapy, will bring about targeted therapeutics to treat diseases of the central nervous system.

Nancy Stagliano, Ph.D
Nancy Stagliano, PhD is CEO and Board Chair of Neuron23. Nancy has always been driven by her love of science and medicine, receiving a PhD in neuroscience, and degrees in both biomedical and electrical engineering, followed by a postdoc at Harvard Medical School. “Of all parts of the body, to me it is the most interesting and the most complex,” she explains. “I think the brain is the final frontier.”

It was a powerful moment when I realized how quickly a neurodegenerative disease can progress.

Nancy Stagliano, PhD, CEO and Board Chair of Neuron23

Finding what triggers Parkinson’s disease

Precision medicine, for many, is the holy grail of healthcare. Being able to treat patients with diseases like cancer using therapies tailored specifically to them is the vision of scientists worldwide working in this field. 

But personalized medicine is not possible without companion diagnostics, and almost every targeted therapeutic today comes with a companion diagnostic. These tests detect clinically relevant genetic abnormalities and help doctors to quickly and accurately identify the treatments to which a particular individual is most likely to respond. 

“We take our cues from what people have done for decades in oncology by attempting to address grievous diseases like Parkinson’s or multiplesclerosis (MS) with an approach that is more patient-specific – or will at least help identify a subset of patients that will benefit from a drug,” Stagliano explains.

Neuron23’s main focus is currently Parkinson’s, one of the most severe neurodegenerative disorders with no cure. Therapies are used to alleviate some symptoms, but there are no existing therapies that modify the progression of the disease. 

While genetics is thought to play a role in Parkinson’s, in most cases the illness does not seem to run in families. Most researchers now believe Parkinson’s results from a complex combination of genetic susceptibility and environmental factors.

Sam Jackson

Sam Jackson, M.D., MBA,  joined Neuron23 in 2022. Jackson is a board-certified emergency physician with fellowship training in medical toxicology. He is driven by “the potential to bring next-generation personalized therapies to patients with limited treatment options“. Identifying Parkinson’s disease patients likely to respond to a therapy with companion diagnostics will be a milestone for the startup, since companion diagnostics have never been developed for neurodegenerative diseases.

This has the potential to provide tremendous value for patients and their families. We want to make sure that the right patients are getting the right drug.

Sam Jackson, M.D., Chief Medical Officer, Neuron23

The first clinical candidate

In 2022, Neuron23 nominated its very first clinical candidate, named NEU-723. It is a small molecule drug designed to inhibit the LRRK2 activity associated with Parkinson’s as well as systemic inflammatory diseases like inflammatory bowel disease and leprosy. 

Mutations in this gene are one of the most common causes of familial Parkinson’s disease. There is also emerging evidence that LRRK2 activity may play a role in a subset of the larger population of patients with nonfamilial Parkinson’s disease.

Neuron23, which has numerous LRRK2 candidates in its pipeline, is testing the hypothesis that LRRK2 inhibition will slow the disease. “We are not talking about a cure, but we are aiming for a therapy that will slow the rate of decline – a disease modification,” says Sam Jackson, M.D., Neuron23’s Chief Medical Officer. “This has the potential to provide tremendous value for patients and their families. We want to make sure that the right patients are getting the right drug.”

But while Neuron23 knew that it wanted to tackle this complex problem, finding a partner to develop the necessary companion diagnostic proved to be difficult. “We wanted to find a partner who shares our vision to change the field and develop companion diagnostics for neurodegenerative diseases,” says Luc Desnoyers, PhD, Vice President of Translational Research and Discovery (R&D) at Neuron23.

He interviewed more than 25 companies to find the right partner until he found it in QIAGEN. “QIAGEN shares our vision that companion diagnostics in neurodegenerative diseases are important and critical,” he explains.

Neuroscience, CNS disorders, Parkinson and Alzheimers
Next-generation sequencing (NGS), which can identify specific biomarkers (1000s of single nucleotide polymorphism - SNPs) in patients, has been instrumental in getting finer profiles. “We can't get to the brain,” explains Stagliano,” but we can get to the CSF (cerebrospinal fluid). I do think that the study of that fluid sample with really high-resolution and high-sensitivity analysis will allow us to get closer to what's happening, what's going wrong.”

Instead of just treating a few percent of Parkinson’s patients, we will treat one-third of Parkinson’s patients.

Nancy Stagliano, PhD, CEO and Board Chair of Neuron23

A collaboration to slow the disease

In 2022, Neuron23 and QIAGEN announced their collaboration to develop a companion diagnostic– the first to be developed for Parkinson’s, says Stagliano. QIAGEN will develop and validate a clinical trial assay that will detect a combination of genetic markers discovered by Neuron23 that together predict the responsiveness of Parkinson’s disease patients to a LRRK2 inhibitor. 

The test will employ next-generation sequencing (NGS) from QIAGEN and dig through each patient’s genome to spot the biomarkers that Neuron23 has linked with responsiveness to ist LRRK2 inhibitor.

Identifying Parkinson’s disease patients likely to respond to a therapy with companion diagnostics will be a milestone for the startup, since companion diagnostics have never been developed for neurodegenerative diseases.

According to Jackson, missense mutations, or changes in DNA that result in different amino acids being encoded at a particular position in the resulting protein in the LRRK2 gene, cause only about 1–2% of Parkinson’s disease in the US. But there is another, larger group of Parkinson’s disease patients that do not have these identified missense mutations in the LRRK2 gene, but instead have dysfunction in the LRRK2 pathway that contributes to their disease.

With the work that Neuron23 is doing with QIAGEN, the startup will be able to find individuals who are in this group. Stagliano and her 45-strong team think that the group of patients that could benefit from this therapy is between 25% and 35%. “So now, instead of just treating a few percent of Parkinson’s patients, we will treat one-third of Parkinson’s patients,” Stagliano says, “and we think that they will likely respond.”

With the work that Neuron23 is doing with QIAGEN, the startup will be able to find individuals who have dysfunction in the LRRK2 pathway that contributes to their disease. “We were able to work with QIAGEN to develop a program to develop this companion diagnostic that support the development of the technical aspect of the assay to read the SNPs,” says Stagliano. Stagliano and her team think that the group of patients that could benefit from this therapy is as high as 25% to 35%.

September 2023

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