Azad M. Madni, Ph.D., NAE
University Professor
GIBT Affiliate

Under a medical research award from the Marcus Foundation, the CPCB-RPE1 retinal implant is being developed by Dr. Mark Humayun and his team for patients with geographic atrophy, a form of advanced macular degeneration. The Marcus Foundation funds and partners with organizations that are making a difference in the delivery of community food resources or are expanding the understanding and implementation of sustainability. Bernie Marcus of the Marcus Foundation is one of the three founders of Home Depot.

Geographic atrophy is a condition which inevitably progresses to severely impaired vision and ultimately legal blindness. Unlike other approaches including the recent FDA approved injection of medications from the company Apellis, these approaches focus on slowing the progression of the disease and often vision continues to deteriorate. The CPCB-RPE1 implant (see Figure 1) currently under development by Dr Humayun’s team and their collaborators is a unique, first-in-field product that is specifically focused on improving the vision of patients with GA.

The development of the implant is based on a transdisciplinary systems approach that accounts for the interactions and interdependencies among the contributing disciplines while also addressing downstream concerns such as manufacturing, delivery, cost and worldwide distribution from the outset.

Clinical trials of the implant are expected to start in the next year at multiple sites in subjects who have GA. Patients receiving the implant will be evaluated using FDA-cleared safety and efficacy endpoints. Pursuant to demonstrating implant safety and efficacy, randomized clinical trials for the registration of the implant will commence with the goal to obtain FDA approval. In keeping with a systems thinking mindset, both patient and healthcare considerations have been addressed and appropriate measures have been built into the product to facilitate widescale adoption within both the ophthalmologist and patient communities. For example, the surgical implementation procedure has been designed to exploit techniques such as vitrectomy and retinotomy commonly used by retinal surgeons. Along the same lines, a custom-designed delivery tool has been developed and successfully implemented to facilitate targeted delivery of the implant to the geographic area, while ensuring that the implant is protected from damage during the procedure. As important, to facilitate widespread distribution, a cryopreserved formulation of the implant has been developed to ensure product shelf-life longevity thereby vastly simplifying scheduling, delivery and shipment of the implant. Also, the use of long-term storage solutions makes scaled manufacturing of the implant practical. Furthermore, in the light of ongoing work by the Advanced Regenerative Medicine Institute (ARMI), a non-profit primarily funded by the Defense Department, future automation of the manufacturing process is entirely feasible to fulfill the growing market demand at significantly reduced cost. Finally, the cost of the implant has been a driver throughout development. At today’s manufacturing scale, an implant is expected to cost approximately $10,000. Using a conservative two-fold to five-fold reduction in costs with scale-up and manufacturing, the cost of the implant could potentially be reduced to $2k to $5k.

In sum, the CPCG-RPE1 implant is a potential “game-changer.” It is being designed to be affordable while satisfying the patient’s unmet need for which there are no approved therapies to-date.

USC Center for Neuronal Longevity (CNL) Pursues Transformative Advance in Prevention and Treatment of Neurodegenerative Diseases

By Azad M. Madni, GIBT Affiliated Faculty

The USC Center for Neuronal Longevity (CNL) has a specific mission: become a world-leading center of excellence with a focus on creating adaptive, interventional bioengineered systems for delivering electromagnetic fields to prevent and treat prevalent neurodegenerative diseases of the brain and retina that today have no foreseeable cure. 

Led by Mark Humayun, MD, PhD, and a team of world-class researchers with expertise in complementary disciplines, the center is pursuing a game-changing advance in preventing neuronal loss in neurodegenerative diseases. Unlike existing approaches that focus on developing neuroprosthesis by bypassing damaged tissues to restore senses such as hearing and sight and reduce Parkinson tremor, the CNL approach focuses on achieving “neuronal longevity” by preventing neuronal loss in neurodegenerative diseases. This research focus is based on a single key insight: lost neurons cannot be restored. CNL intends to create a new class of microscale and nanoscale engineered systems that, in their final incarnation will be controllable in part by widely available portable devices. These systems, embodying this key advance, are expected to induce primary healing and/or prevent further neuronal and functional loss. 

Gianluca Lazzi, PhD, and Arthur Toga, PhD serve as CNL deputy directors, bringing their scientific expertise and track records in leading successful interdisciplinary initiatives and institutes to CNL’s management structure. CNL’s convergent research themes are specifically intended to fill gaps and overcome limitations in existing technologies, while at the same time increasing understanding of molecular mechanisms involved in neuroprotection. The resulting “bioengineered systems for neuronal longevity” will exploit CNL’s expertise in engineering, neuroscience, data science, material science, and medicine in conjunction with deep knowledge of biology and biochemistry. Equally important, the CNL team’s expertise in STEM education and pedagogy will assure effective knowledge transfer within the team.

The key research pillars of CNL are:

  1. a systemic focus rooted in extending neuronal longevity, a departure from today’s corrective strategy that calls for bypassing damaged tissues
  2. a transdisciplinary team of researchers with complementary expertise and synergistic goals to pursue this revolutionary advance
  3. a combination of testbeds that enable the realization of bioengineered systems for controlled remodeling of the retina to treat blindness, and bioengineered multi-model stimulation systems to prevent neuronal degeneration
  4. an innovative workforce development strategy that accelerates the development of an interdisciplinary workforce that reflects diversity and a culture of inclusion

The CNL intends to accomplish both societal and scientific impact by minimizing the annual economic burden of neurodegeneration, while accelerating discovery of novel bioengineered systems and creation of new tools for collaborative technology validation. For additional information on CNL, please contact:

Clinical Trial Shows Promising Outcomes for Vision Loss Patients Receiving Stem Cell Implants

Researchers at the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics recently reported promising one-year follow up results of a clinical trial using stem cells to treat vision loss.

The phase 1/2a trial set out to assess the safety of a stem cell-based retinal implant the USC Ginsburg Institute team developed to treat dry age-related macular degeneration (dry AMD), which is one of the leading causes of vision loss. A total of 15 patients with severe vision loss underwent surgery at Keck Medicine of USC to receive a stem cell-based implant in their worse- seeing eye. One-year follow up results demonstrated that the implant was not only safe and well-tolerated, but also helped improve vision in its recipients.

Stem cells to rescue a degenerating eye

The disease process of dry AMD involves deterioration of a layer of cells called the retinal pigment epithelium (RPE). RPE cells nourish and support the photoreceptor cells that enable us to perceive light, so when they degenerate, eyesight follows suit. There are currently few medical interventions for the millions of patients who suffer from dry AMD, and given enough time, the disease ultimately progresses to blindness.

Physician-scientists at the USC Ginsburg Institute sought to revolutionize the treatment landscape for dry AMD by utilizing stem cells to replenish the deteriorating RPE cell layer of the retina. To do so, the research team developed a small scaffold made of synthetic material that is safe within the human body and can harbor RPE cells grown from stem cells in a lab. The scaffold is shaped like a champagne bottle and can be inserted into a patient’s retina using a precision tool designed by surgeon-scientists Amir Kashani, MD, PhD and Mark Humayun, MD, PhD at the USC Ginsburg Institute.

Restored sight on the horizons

Clinical trial patients receiving this novel implant were followed for a year post-operation and monitored for any health complications. Prior to surgery, all patients had severe, end-stage forms of dry AMD and were considered legally blind. The trial demonstrated that the implant can be used safely in dry AMD patients, and promisingly, it even resulted in improvements in eyesight in several cases. To help explain the mechanism by which trial patients achieved improvements in visual acuity, the researchers proposed that “dormant” photoreceptor cells in the degenerating area of the retina may be revived by the stem-cell derived implant.

This effort represents the first-ever clinical trial of a retinal implant to treat dry AMD. Its promising early outcomes will pave the way for future studies assessing the implant’s ability to restore eyesight in a much larger cohort of patients, with the ultimate goal of achieving FDA approval as a novel therapeutic for dry AMD.

“We are very hopeful about the results and future directions of this trial,” Humayun said. “There is currently a major unmet clinical need for treatments to help patients suffering from dry AMD, and this stem cell-based therapy represents a large stride in the right direction.”