Stem Cell Agency Approves Funding for Clinical Trials Targeting Parkinson’s Disease and Blindness

The governing Board of the California Institute for Regenerative Medicine (CIRM) yesterday invested $32.92 million to fund the Stem Cell Agency’s first clinical trial in Parkinson’s disease (PD), and to support three clinical trials targeting different forms of vision loss.

This brings the total number of clinical trials funded by CIRM to 60.

The PD trial will be carried out by Dr. Krystof Bankiewicz at Brain Neurotherapy Bio, Inc. He is using a gene therapy approach to promote the production of a protein called GDNF, which is best known for its ability to protect dopaminergic neurons, the kind of cell damaged by Parkinson’s. The approach seeks to increase dopamine production in the brain, alleviating PD symptoms and potentially slowing down the disease progress.

David Higgins, PhD, a CIRM Board member and patient advocate for Parkinson’s says there is a real need for new approaches to treating the disease. In the US alone, approximately 60,000 people are diagnosed with PD each year and it is expected that almost one million people will be living with the disease by 2020.

“Parkinson’s Disease is a serious unmet medical need and, for reasons we don’t fully understand, its prevalence is increasing. There’s always more outstanding research to fund than there is money to fund it. The GDNF approach represents one ‘class’ of potential therapies for Parkinson’s Disease and has the potential to address issues that are even broader than this specific therapy alone.”

The Board also approved funding for two clinical trials targeting retinitis pigmentosa (RP), a blinding eye disease that affects approximately 150,000 individuals in the US and 1.5 million people around the world. It is caused by the destruction of light-sensing cells in the back of the eye known as photoreceptors.  This leads to gradual vision loss and eventually blindness.  There are currently no effective treatments for RP.

Dr. Henry Klassen and his team at jCyte are injecting human retinal progenitor cells (hRPCs), into the vitreous cavity, a gel-filled space located in between the front and back part of the eye. The proposed mechanism of action is that hRPCs secrete neurotrophic factors that preserve, protect and even reactivate the photoreceptors, reversing the course of the disease.

CIRM has supported early development of Dr. Klassen’s approach as well as preclinical studies and two previous clinical trials.  The US Food and Drug Administration (FDA) has granted jCyte Regenerative Medicine Advanced Therapy (RMAT) designation based on the early clinical data for this severe unmet medical need, thus making the program eligible for expedited review and approval.

The other project targeting RP is led by Dr. Clive Svendsen from the Cedars-Sinai Regenerative Medicine Institute. In this approach, human neural progenitor cells (hNPCs) are transplanted to the back of the eye of RP patients. The goal is that the transplanted hNPCs will integrate and create a protective layer of cells that prevent destruction of the adjacent photoreceptors. 

The third trial focused on vision destroying diseases is led by Dr. Sophie Deng at the University of California Los Angeles (UCLA). Dr. Deng’s clinical trial addresses blinding corneal disease by targeting limbal stem cell deficiency (LSCD). Under healthy conditions, limbal stem cells (LSCs) continuously regenerate the cornea, the clear front surface of the eye that refracts light entering the eye and is responsible for the majority of the optical power. Without adequate limbal cells , inflammation, scarring, eye pain, loss of corneal clarity and gradual vision loss can occur. Dr. Deng’s team will expand the patient’s own remaining LSCs for transplantation and will use  novel diagnostic methods to assess the severity of LSCD and patient responses to treatment. This clinical trial builds upon previous CIRM-funded work, which includes early translational and late stage preclinical projects.

“CIRM funds and accelerates promising early stage research, through development and to clinical trials,” says Maria T. Millan, MD, President and CEO of CIRM. “Programs, such as those funded today, that were novel stem cell or gene therapy approaches addressing a small number of patients, often have difficulty attracting early investment and funding. CIRM’s role is to de-risk these novel regenerative medicine approaches that are based on rigorous science and have the potential to address unmet medical needs. By de-risking programs, CIRM has enabled our portfolio programs to gain significant downstream industry funding and partnership.”

CIRM Board also awarded $5.53 million to Dr. Rosa Bacchetta at Stanford to complete work necessary to conduct a clinical trial for IPEX syndrome, a rare disease caused by mutations in the FOXP3 gene. Immune cells called regulatory T Cells normally function to protect tissues from damage but in patients with IPEX syndrome, lack of functional Tregs render the body’s own tissues and organs to autoimmune attack that could be fatal in early childhood.  Current treatment options include a bone marrow transplant which is limited by available donors and graft versus host disease and immune suppressive drugs that are only partially effective. Dr. Rosa Bacchetta and her team at Stanford will use gene therapy to insert a normal version of the FOXP3 gene into the patient’s own T Cells to restore the normal function of regulatory T Cells.

The CIRM Board also approved investing $15.80 million in four awards in the Translational Research program. The goal of this program is to help promising projects complete the testing needed to begin talking to the US Food and Drug Administration (FDA) about holding a clinical trial.

The TRAN1 Awards are summarized in the table below:

ApplicationTitleInstitutionAward Amount
TRAN1 11536Ex Vivo Gene Editing of Human Hematopoietic Stem Cells for the Treatment of X-Linked Hyper IgM Syndrome  UCLA $4,896,628
TRAN1 11555BCMA/CS1 Bispecific CAR-T Cell Therapy to Prevent Antigen Escape in Multiple Myeloma  UCLA $3,176,805
TRAN1 11544 Neural Stem cell-mediated oncolytic immunotherapy for ovarian cancer  City of Hope $2,873,262
TRAN1 11611Development of a human stem cell-derived inhibitory neuron therapeutic for the treatment of chronic focal epilepsyNeurona Therapeutics$4,848,750

Mutation Morphs Mitochondria in Models of Parkinson’s Disease, CIRM-Funded Study Finds

There is no singular cause of Parkinson’s disease, but many—making this disease so difficult to understand and, as a result, treat. But now, researchers at the Buck Institute for Research on Aging have tracked down precisely how a genetic change, or mutation, can lead to a common form of the disease. The results, published last week in the journal Stem Cell Reports, point to new and improved strategies at tackling the underlying processes that lead to Parkinson’s.

Mitochondria from iPSC-derived neurons. On the left is a neuron derived from a healthy individual, while the image on the right shows a neuron derived from someone with the Park2 mutation, the most common mutation in Parkinson's disease (Credit: Akos Gerencser)

Mitochondria from iPSC-derived neurons. On the left is a neuron derived from a healthy individual, while the image on the right shows a neuron derived from someone with the Park2 mutation, the most common mutation in Parkinson’s disease (Credit: Akos Gerencser)

The debilitating symptoms of Parkinson’s—most notably stiffness and tremors that progress over time, making it difficult for patients to walk, write or perform other simple tasks—can in large part be linked to the death of neurons that secrete the hormone dopamine. Studies involving fruit flies in the lab had identified mitochondria, cellular ‘workhorses’ that churn out energy, as a key factor in neuronal death. But this hypothesis had not been tested using human cells.

Now, scientists at the Buck Institute have replicated the process in human cells, with the help of stem cells derived from patients suffering from Parkinson’s, a technique called induced pluripotent stem cell technology, or iPSC technology. These newly developed neurons exactly mimic the disease at the cellular level. This so-called ‘disease in a dish’ is one of the most promising applications of stem cell technology.

“If we can find existing drugs or develop new ones that prevent damage to the mitochondria we would have a potential treatment for PD,” said Dr. Xianmin Zeng, the study’s senior author, in a press release.

And by using this technology, the Buck Institute team confirmed that the same process that occurred in fruit fly cells also occurred in human cells. Specifically, the team found that a particular mutation in these cells, called Park2, altered both the structure and function of mitochondria inside each cell, setting off a chain reaction that leads to the neurons’ inability to produce dopamine and, ultimately, the death of the neuron itself.

This study, which was funded in part by a grant from CIRM, could be critical in the search for a cure for a disease that, as of yet, has none. Current treatment regimens aimed at slowing or reducing symptoms have had some success, but most begin to fail overtime—or come with significant negative side effects. The hope, says Zeng, is that iPSC technology can be the key to fast-tracking promising drugs that can actually target the disease’s underlying causes, and not just their overt symptoms. Hear more from Dr. Xianmin Zeng as she answers your questions about Parkinson’s disease and stem cell research: