Stroke Leaders Unite
Clinical Trails for Cell-Based Therapies in Stroke
World Leaders Gather in Washington D.C.
By Keri Kimler | December 10th, 2011
A stroke leaves a permanent gap in the brain that can destroy a person’s ability to speak and move normally. The good news? This may not have to be permanent in the not too distant future. Dr. Francis Collins, director of the National Institutes of Health (NIH), said it best in 2010, “The possibility of using these cells to replace those that have been damaged by disease or injury is one of the most breathtaking advances we can envision.”
This month I was invited to attend a historic conference that brought together industry leaders, research investigators, and members of the NIH and FDA into a single forum to discuss cell-based therapies in stroke. Dr. Sean Savitz, conference program director and Director of Cellular Therapy and Translational Stroke Research at the University of Texas Medical School at Houston, welcomed a prestigious, multidisciplinary group from around the globe to a unique conference held in Washington D.C., December 3-4. The conference was called “Enhancing the Development of Clinical Trials for Cell-Based Therapies in Stroke.”
Upon return, I came across an article on the NIH website published recently in Stem Cells Translational Medicine that echoes the spirit of this enlightening meeting very eloquently. “From our vantage point, it appears that the field of regenerative medicine has moved out of the rocky shallows and is rapidly sailing towards the therapeutic mainstream.”
My review of the meeting from an advocate’s perspective…
The first day of the conference included a series of lectures by distinguished leaders in the field and covered the gamut of key basic science, translational and clinical trial issues. The second day was devoted to a series of workshops for participants to discuss and provide recommendations for guidelines on important research topics in the field that will later be published.
The meeting opened with a history overview of the group’s past conferences, STAIR and STEPS, by Dr. Savitz as well as a briefing on the conference goals.
The first session, chaired by Dr. Michael Chopp, an internationally recognized expert in the development and treatment of stroke and professor at Henry Ford Hospital, focused on biological mechanisms and began with a presentation from Dr. Cesar Borlongan, University of South Florida (USCF), on the expanding universe of available cell types. His colleague, Allison Willing reviewed the peripheral activities of cell therapy and Eva Mezey, head of the adult stem cell unit at the National Institute of Dental and Craniofacial Research (NIDCR), discussed immunomodulation. The session ended with UCLA’s Tom Carmichael, MD, PhD discussing current research and concepts related to neurogenesis and angiogenesis. All sessions were followed by moderated roundtable discussions.
Challenges in Translation, a session chaired by Johannes Boltze, MD, head of the Department of Cell Therapy at Fraunhofer Institute in Germany, immediately followed and included presentations by Dr. Raphael Guzman and Gary Steinberg, MD, PhD, both professors of Neurosurgery at Stanford University School of Medicine and Panayiotis Mitsias, MD, Henry Ford Health Sciences Center. Testing the safety of intra-arterial delivery, biological targets of cell therapy for stroke, and an overview of imaging markers were covered in this session.
Cellular therapy, including the use of stem cells, is a promising new investigational approach for the treatment of both acute and chronic stroke. Through pre-clinical studies, Savitz and other investigators have found that many types of cell therapies may have the potential to benefit patients who are still in the acute phase of their stroke. Strategies for designing both intravenous studies and intra-arterial studies in acute stroke were covered during the third session by Savitz and Dr. Dileep Yavagal, Director of Interventional Neurology at the University of Miami led these discussions.
We then moved from acute stroke to chronic stroke, chaired by Evan Snyder, Sanford-Burnham Medical Research Institute where Dr. Casey Case, vice president of research at SanBio eloquently covered the rationale for cell therapy and Dr. Doug Kondziolka, University of Pittsburgh demonstrated intracranial delivery methods. Marcel Dihné gave an update on neural stem cells and Dr. Keith Muir concluded the session with a comprehensive review of the current clinical trials.
The final session of the day, Stroke Outcomes in Clinical Trials, chaired by Pam Duncan, Ph.D., P.T at Duke Center for Aging began with a review by Steve Cramer, University of California Irvine, entitled “Principles of human brain repair as they pertain to cell therapies,” followed by a presentation on “Traditional Endpoints vs. Domain-Specific Endpoints in clinical trials” by Seth Finkelstein, Chairman and Chief Scientific Officer at Biotrofix, Inc and associate neurologist at Massachusetts General.
Lei Xu, Office of Cellular, Tissue and Gene Therapy (OCGCT) at FDA‘s Center for Biologics Evaluation and Research (CBER) evaluation division (DCEPT) shared the current perspectives of the agency on endpoint selection for efficacy studies as well as useful insights into label indications. The final presentation by FDAs product reviewer, Tom Finn, PhD, “Cell production pathway from initial studies to phase III trials” ended the day and set the stage for the following day’s breakout workshops.
The discussions carried well into the evening as everyone processed the data download and synthesized the detailed information presented by their peers. These are the moments that I wish I could record and play back for you. Woven through the fabric of highly complex scientific conversation is an undeniable focus on the well being of patients. The basic scientists and clinical researchers alike are operating with an eye toward health care—emphasis on “care.”
On Day Two, the group broke into two workshops to develop consensus recommendations for establishing Guidelines for Chronic Stroke and guidelines for Phase II/III Trials of Cell Therapy for Stroke. Larry Wechsler, MD chaired the Chronic Stroke Guidelines appropriateness of initial safety testing in chronic stroke. The group also reviewed the various workshop and the participants discussed how cells could be used to enhance recovery according to their distinct biological mechanisms, the need for preclinical support, models currently available, and appropriateness of initial safety testing in chronic stroke. The group also reviewed the various delivery routes and recommendations for outcome measures.
The second workshop, Phase II/III Trials of Cell Therapy for Stroke, was led by Steve Cramer and included discussions of patient selection and feasibility of acute time windows, global scales vs. domain specific scales, standardizing rehab strategies, considerations for comparison and combination studies with other rehab modalities and FDA approved labels.
After two very interactive breakout sessions, the group reunited and the workshop chairs presented the
This conference was very well organized and the feedback by the participants was overwhelmingly positive. As an advocate for responsible research that holds so much promise for relieving suffering and providing solutions for diseases like stroke, it is encouraging to see the commitment by world leaders to working together to move science forward for the benefit of patients.
I wish everyone could have an opportunity to listen to these presentations and witness the true spirit of collaboration between doctors, researchers, scientists, radiologists, industry leaders and representatives of our government agencies.
We are in very good hands if this group continues to make the effort that I witnessed in Washington, DC. Our health care future looks brighter from my vantage point and I am certain this meeting will enhance the development of well-designed clinical trials that will lead to safe and effective cell-based therapies for millions suffering from a stroke.