The Cell & Gene Start-ups Revolutionising Neurodegenerative Disease Treatment.

Cell and gene therapy is becoming a proven success due to its ability to provide a highly personalised approach and longer-lasting results. Thanks to various innovative companies paving the way in this field, new strains of medical research are testing the effect of this application on more complex diseases.

After my colleague, Spencer, mentioned some key market innovators in a recent article I was intrigued and began to dig deeper into emerging treatments in the neurodegenerative disease space. I stumbled upon some innovative budding companies due to gain official status in the coming year, so took a closer look at what this means for the future of the industry.

As these companies are mostly in the late stages of development or early testing phases, I am keen to highlight their innovative approach to treating irreversible neurological diseases and the potential impact their new products could have on the wider industry.

Verge Genomics

Founded by industry innovator and multi-award winner, Alice Zhang, Verge Genomics is a pre-clinal biotechnology company creating next-generation medicines from human genomics. Focussing specifically on new medical solutions for degenerative neurological diseases, Verge’s USP heroes their use of machine learning to develop a drug which can successfully target all genes at once. This is an industry first in comparison to the current strategy of continuous blanket testing to target one gene at a time. By taking the ‘guesswork’ out of their production strategy, Verge dramatically reduces the cost and time taken to produce new drugs and hopes to automate the discovery of cures to create better drugs, faster than ever before.

Verge will receive up to $25 million in upfront, equity investment to fund further development of their AI algorithms. This, combined with their large library of human data, sees them reach the IND-enabling phase for a transformative Amyotrophic Lateral Sclerosis (ALS) treatment which, if successful, is predicted to progress to human trials in 2022.

As one of the world’s most invasive neurological diseases, ALS targets nerve cells in the brain and spinal cord to cause progressive loss of muscle control. One of the biggest challenges in the treatment of ALS is the complex biology and lack of predictive animal models, however Verge’s breakthrough therapies harness recent advances in genetic sequencing and human tissue banking to drive forwards solutions for complex diseases like ALS.

Voyager Therapeutics

Another new company undertaking pre-clinical studies with positive results is Voyager Therapeutics. Their next-generation AAV capsid platform, TRACER, uses a directed evolution approach to identify novel capsids (virus protein shells) with improved ability to target specific cells and tissues. These are often difficult to reach with current gene therapy delivery methods, making this new method of detection a potentially industry defining development.

Huntington’s disease is a neurodegenerative disorder caused by mutations in the huntingtin (HTT) gene. This results in an abnormally large production of HTT protein accumulating inside nerve cells and causing their death. Voyager’s VY-HTT01 is a type of gene silencing therapy aimed at addressing the underlying cause of the disease, significantly reducing the amount of damaging HTT protein produced.

Thanks to its “RNA interference” system, VY-HTT01 can create a pathway to regulate protein production. Alongside the adeno-associated viral (AAV) vector, a modified virus that can deliver genetic material into brain cells, the drug acts as a promotor and miRNA transgene working against the HTT mRNA. With less toxic HTT, nerve cell death should be reduced and prevent the progression of Huntington’s disease.

Sio Gene Therapies

Parkinson’s is a progressive neurodegenerative disorder caused by the loss of dopamine signalling in the brain, resulting in the continual decline of motor control. Whilst there is currently no cure, dopaminergic strategies that temporarily increase dopamine levels in the brain can help short-term improvement in symptoms and slow down progression.

Sio Gene Therapies is a clinical-stage company focussed on gene therapy treatments for debilitating neurodegenerative diseases. Their AXO-Lenti-PD is an investigational gene therapy already in Phase 2 trials for Parkinson’s disease.

As the only gene therapy of its kind to carry three key enzymes for dopamine synthesis (TH, CH1 & AADC), AXO-Lenti-PD requires administration via a one-time dopamine infusion. Initial clinical data demonstrates that this single dose “turns back the clock”. Benefits include improved motor function, reducing the need for daily medication and stabilising progression.

Trials show outcomes where patients become able to undertake daily tasks after six months of treatment, a major transformative breakthrough for Parkinson’s drug development. With $119 million left in funding in 2021 it is predicted operations will be sustained into 2022. This gives time to get this revolutionary product to market, an exciting feat for the company and industry.

Aspen Neuroscience

Another company advancing Parkinson’s drug development via a different method is Aspen Neuroscience. Their experimental ‘pluripotent’ stem cell approach, a technique which won the 2012 Nobel Prize for medicine, uses skin cells transplanted from current Parkinson’s patient’s cells through the introduction of an inert viral RNA to replace those the disease has destroyed.

Having recently raised $70 million to advance the development of Parkinson’s disease therapies using this method, Aspen Neuroscience will focus their sites on developing products ANPD001 and ANPD002. Both use ‘autologous neuron replacement therapy’ and are set to be the first-ever Parkinson’s treatments designed to use a patient’s own cells as a replacement for damaged ones, restoring neuronal function and modifying disease progression.

Whilst the first of the two is undergoing IND-enabling studies for treatment of sporadic forms of Parkinson’s, the second product uses gene correction and neuron therapy to treat genetic forms of the disease. Aspen’s financing is forecast to support the completion of all remaining investigational studies and FDA submission, alongside data collection from a Phase 1 clinical trial and expansion into Phase 2 randomized studies, meaning they are certainly one to watch in the coming months.

Neurona Therapeutics

Another company at an advanced pre-clinical stage of a ‘pluripotent’ stem cell development is Neurona Therapeutics. This biotherapeutics company uses restorative neural cell therapies to treat chronic neurological disorders. Their most advanced treatment is one for epilepsy, called NRTX-1001, which progresses to the next phase of research and development after the company successfully secured $41.5 million in funding in 2021.

This repressive neuron cell therapy is developed in response to the lack of treatment for drug-resistant focal epilepsy. This severe level of epilepsy means seizures are sometimes uncontrollable with use of antiseizure medications alone. Misdiagnosis or incorrect drug dosage are common contributors; however, these uncertainties highlight the opportunity for development of a more specific solution.

Neurona aims to use their patented manufacturing process to deliver just a single dose with curative potential. This process distributes inhibitory neurons which integrate to rebalance and repair the hyperexcitable neural networks, the underlying cause of epileptic fits.

What’s next?

After discovering more about the ongoing progression of these companies, I’m really intrigued to see how these innovative medical advances will affect the futures of both the industry and those suffering with these life-changing diseases. Should these products appear in the market in the coming years as predicted, the landscape is likely to see vast and impactful change and growth, bringing exciting opportunities alongside the rollout of these products.

Are you similarly intrigued by what’s next for the industry? I’d love to chat through this some more, get in touch with me at chikondi.banda@charltonmorris.com.