Three CIRM-funded approaches advance potential Parkinson’s treatments

/ California Institute for Regenerative Medicine (CIRM)

Holding a curved device that looked a bit like a mariner’s sextant, neurosurgeon Warren Boling explained how he’ll use it to precisely deliver a new gene therapy deep into the brains of Parkinson’s patients participating in a pivotal clinical trial.

A colony of iPSCs from a Parkinson’s patient (left) and dopaminergic neurons made from these iPSCs (right) to model PD. (Image credit: Jeanne Loring)

Dr. Boling, the chair of neurosurgery at Loma Linda University Health, described the procedure during a recent visit by representatives of the California Institute for Regenerative Medicine (CIRM). CIRM helps support the clinical trial site at Loma Linda, one of now a dozen sites across California that are part of the CIRM Clinical Care Network

Competing strategies

This experimental treatment was developed by AskBio using foundational research from Dr. Krystof Bankiewicz at UCSF. The work at UCSF was supported by a $5 million CIRM grant. Although the clinical trial itself is not funded by CIRM, the agency supports the Loma Linda trial site through the Clinical Care Network.

This experimental treatment, which Boling will deliver from AskBio, is one of three CIRM-funded approaches in clinical trials for Parkinson’s disease. Parkinson’s disease is a neurodegenerative condition that affects more than 10 million people worldwide. The disease results in a loss of dopamine in the brain, which is critical in a person’s ability to control movement.

Like AskBio, the other potential treatments — from Aspen Neuroscience and Kenai Therapeutics — have now advanced into clinical trials. All three treatments require highly trained neurosurgeons using live imaging to surgically implant the therapy into a critical region of the brain.

It’s unclear which of the three treatments, if any, has the best chance for success. But the hope is that at least one, or all of them, could transform the treatment of Parkinson’s disease.

The best chance for success

CIRM’s sustained support for Parkinson’s spans early discovery research, clinical development, and now multiple therapeutic approaches. To date, CIRM has invested more than $111 million specifically into Parkinson’s research and therapy development. These three potential treatments amount to only a small percentage of that total.

Supporting more than one approach to treat Parkinson’s offers a better opportunity for success.

“Our best chance for developing better treatments for Parkinson’s is to test as many logical approaches as possible,” said former CIRM Board Member and Parkinson’s patient advocate David Higgins, Ph.D.

Now, more than six years since Higgins made those comments, these three potential treatments are being tested in people. These three programs also offer examples of CIRM’s role in helping to accelerate cell and gene therapy in California.

More on Parkinsons

Parkinson’s is the second most common neurodegenerative disease after Alzheimer’s. About 10 million people worldwide live with Parkinson’s, and more than a million of those are in the United States. California has about 116,000 people with the disease.  In a small percentage of Parkinson’s cases, the cause is a mutation in known genes, leading to an earlier onset. In the majority of cases, the cause is unknown, and the disease may take longer to appear, but the impact is the same.

Parkinson’s gradually destroys dopamine-producing cells. Dopamine is a neurotransmitter that helps the brain regulate movement and cognition, along with other functions. As these cells die off, the brain loses its ability to control movement properly, leading to symptoms such as tremor, rigidity, and slowed movement. Unfortunately, by the time a person is diagnosed with Parkinson’s, they may have already lost as much as half of their brain’s dopamine-producing neurons.

Medications like levodopa replace dopamine or mimic its effects, and other drugs help preserve dopamine signaling. However, these medications are often difficult to calibrate and not always effective. There are also surgical approaches, including Deep Brain Stimulation, where electrodes are implanted in the brain to help control movements.

While many of the treatments, along with certain lifestyle changes, help patients manage symptoms, none halt the disease’s progression. In the case of many of the medicines, they often work well at first, but over time are less effective.

There is still no cure for Parkinson’s.

Using gene therapy

Although the three CIRM-supported Parkinson’s clinical trials differ, they each aim to restore dopamine production.

The therapy being developed by AskBio originated from CIRM-funded research by Dr. Krystof Bankiewicz, formerly at UCSF but now at Ohio State. He later spun out a company to further develop the gene therapy. That company, Brain Neurotherapy Bio, later became AskBio and is now owned by Bayer. 

The AskBio procedure to be performed at the Loma Linda clinical trial site will be replicated at two other CIRM-supported clinical trial sites in California, as well as at other non-CIRM-affiliated sites across the country and in Europe.

As described by Dr. Bolling, the process involves a neurosurgeon, guided by live brain imaging, delivering the gene therapy AAV2-GDNF into a small, nut-sized area deep in the brain called the putamen. The one-time treatment reprograms cells to revive neurons and jump-start dopamine production in people with Parkinson’s.

Two approaches using cell therapy

Both Aspen Neurosciences and Kenai Therapeutics aim to boost dopamine production using modified cells implanted deep in the brain.

Their treatments reflect two main cell therapy approaches: autologous, which uses a patient’s own cells, and allogeneic, which relies on donor cells.

Aspen’s autologous therapy, ANPD001, reprograms a patient’s skin cells into induced pluripotent stem cells (iPSCs). iPSCs can self‑renew and become any cell type, including dopamine‑producing neurons. This personalized method reduces the risk of rejection.

However, the approach is costly and difficult to scale because each treatment is custom. Even so, Aspen is advancing its ASPIRO Phase 1/2a trial.

Kenai’s allogeneic method uses donor-derived iPSCs to mass-produce dopamine-producing neurons for multiple patients.

This approach is more affordable but requires immune suppression to prevent rejection.

Beyond Parkinson’s, the allogeneic model could help scale other cell therapies.

Kenai is currently in the Phase 1b/2a stage of its REPLACE trial.

In Vivo gene therapy

Like AskBio, another CIRM‑funded approach from NysnoBio bypasses the autologous versus allogeneic debate. The therapy has not yet reached clinical trials.

Parkinson’s often has no known cause, but about half of early‑onset cases involve a Parkin mutation. This mutation damages mitochondria, impairs cell function, and contributes to disease. NysnoBio aims to treat this specific form of Parkinson’s.

NysnoBio’s therapy doesn’t correct the mutation. Instead, it expresses full‑length Parkin protein in multiple cell types within the substantia nigra. Loss of Parkin activity in this region drives Parkinson’s in people with Parkin gene mutations. The therapy aims to restore Parkin protein levels and improve the health of remaining dopamine neurons.

The company’s Parkin gene therapy, NB001, is completing preclinical testing and its investigational new drug study, an essential step before a Phase 1 trial.

What’s next?

Each of these treatments is at different stages of the clinical trials process. Together they’re all focused on a decades-long goal for researchers and patients alike. They all aim to find a lasting treatment or cure for Parkinson’s disease.

This research and other CIRM-supported programs are all focused on finding treatments and cures faster.

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