After several decades of pre-clinical development, cell- and gene-based therapies for Parkinson's disease (PD) are now actively being explored. In this special supplement to the Journal of Parkinson's Disease on "Repairing the Parkinsonian Brain," experts highlight some of the current strategies being pursued to restore lost function and replace what is lost in the PD brain, with special emphasis on the challenges associated with translating advanced therapeutic approaches into pioneering clinical trials.
"Cell and gene therapy for brain diseases have been long in the making, from the first speculative ideas and the first exploratory trials in the 1980s and 1990s to the major setbacks in the cell and gene therapy fields at the turn of the century, followed by the renewed developments seen during the last decade," explained Guest Editors Anders Bjrklund, PhD, Bastiaan R. Bloem, MD, PhD, Patrik Brundin, MD, PhD, and Howard Federoff, MD, PhD.
This revival of the cell and gene therapy field has been driven by the remarkable technical developments that have given us access to increasingly more powerful molecular and genetic tools and techniques. It has opened up far more refined approaches to therapy for neurodegenerative diseases, and PD in particular. This development has gained new momentum over the last few years through the active involvement of the biotech industry, sometimes in partnership with large pharmaceutical companies."
Patrik Brundin, MD, PhD, Co-Guest Editor, Parkinson's Disease Center, Department of Neurodegenerative Science, Van Andel Institute, Grand Rapids, MI, USA
Pioneering trials in this field face regulatory and ethical challenges that are radically different from those applied to conventional drug trials. In Part I on the path to clinical trials for advanced therapies, experts review the challenges involved in the design and conduct of the early clinical trials; the different and complementary perspectives on regulatory and safety requirements; and the design and initiation of first-in-man trials. Ethical issues are explored from the investigator's, scientist's, ethicist's, and patient's perspective. including the patients concerns related to participation as a subject in demanding trials that extend over the long-term, where the outcome and risks are uncertain.
The use of advanced therapy medicinal products (ATMPs) including cell and gene treatments, are reviewed both from the investigator's perspective and the patient's perspective. Roger A. Barker, MBBS, PhD, Department of Clinical Neuroscience, University of Cambridge; and MRC-WT Cambridge Stem Cell Institute, Cambridge, UK, and coauthors point out that investigators taking an ATMP to clinical trials in patients with PD should ask themselves two key questions before embarking on such work: firstly, why are you doing it, and, secondly, do you understand what is needed to conduct a clinical trial with that product. "For ATMPs, there is an enhanced requirement for safety reporting to the regulatory authorities," noted Dr. Barker. "For example, it is imperative when conducting a trial across countries with different regulatory authorities that there is a central reporting process to capture the safety events from the trial."
For patients, a reasonable definition of an ideal advanced therapy is one that addresses one or more unmet needs of patients not covered by existing therapies, treatments with a novel mechanism of action, and most importantly, an intervention that has the potential to be disease-modifying, according to two patient advocates/scientists, Soania Mathur, MD, UnshakeableMD, Oshawa, ON, Canada, and Jon Stamford, PhD, DSc, neuroscientist and independent Parkinson's advocate. They review the issues surrounding engaging the patient community in bringing advanced therapies to the clinic, physician-patient communication, and informed consent from the patient perspective.
Participation in clinical trials and clinical use of advanced therapies have their own risk profile above and beyond standard therapeutics as evidenced by past invasive procedures. Dr. Mathur and Dr. Stamford point out that, "It is of utmost importance that clear, evidence-based information about these potential treatments is clearly communicated by those exploring their use to ensure safe and informed participation from the patient community. Patients must be able to weigh the benefits of these treatments, their limitations, and risks in order to truly give informed consent to participate in bringing these treatments to the clinic."
"The ethical and regulatory issues related to these more advanced treatment modalities are radically different from those involved in standard drug trials in that they must allow for a gradual optimization and perfection of the product, its dosing, and delivery," noted co-Guest Editor Anders Bjrklund, PhD, Wallenberg Neuroscience Center, Lund University, Sweden. "This requires that implementing novel cell- and gene-based therapies is done in a step-wise, incremental manner, which does not easily fit within the standard Phase I-III design of clinical drug trials."
The articles in Part II of this supplement highlight research promoting further development of cell and gene therapies.
Dr. Bjrklund and Malin Parmar, PhD, Department of Experimental Medical Science, Developmental and Regenerative Neurobiology, Wallenberg. Neuroscience Center, Lund University, Lund, Sweden, note that a limitation of the intrastriatal grafting approach, currently in clinical trial, is that the midbrain dopamine neurons are implanted into the target area and not in the ventral midbrain where they normally reside. This ectopic location of the cells may limit their functionality. They review impressive results with implanting the cells into the substantia nigra in rodent PD models as a way to achieve more complete circuitry repair. "This results in a remarkable degree of circuitry reconstruction that far exceeds what has been possible with ectopic intrastriatal grafts and raises the question whether intranigral transplantation should also be explored in human patients," they commented.
Many of the potentially causative and risk associated genes for PD are implicated in lysosomal function or lysosomal trafficking, indicating that lysosome dysfunction is a common denominator underlying PD disease pathology. Franz Hefti, PhD, CEO, Prevail Therapeutics (wholly-owned subsidiary of Eli Lilly and Company), New York, NY, USA, and colleagues, review the latest research on one of the lysosomal genes involved, GBA1, which encodes the lysosomal enzyme glucocerebrosidase (GCase) and has the largest impact on PD risk. Studies in mouse models indicate that a vector-based gene therapy designed to deliver a functional GBA1 gene to the brain may slow or stop disease progression.
"The next breakthrough in the treatment of PD will be based on interventions that block disease progression and restore function back to normal. In this perspective the novel treatment modalities described in this supplement hold great promise," concluded the Guest Editors.
Read this article:
- COVID-19: Researchers warn against overhyping early-stage therapies - Medical News Today - October 26th, 2021
- OpRegen Data Update to Be Featured at 2021 American Academy of Ophthalmology Annual Meeting in Presentation by Michael S. Ip, M.D. - Yahoo Finance - October 26th, 2021
- Insights & Outcomes: Place cells, planarians, and 'prewet' proteins - Yale News - October 26th, 2021
- IMAC Holdings The Back Space Announces the Completion of Two Additional Retail Spinal Care Locations - Yahoo Finance - October 26th, 2021
- JEFFERSON PARISH PARTNERS WITH LOUISIANA DEPARTMENT OF HEALTH TO ADMINISTER FREE FLU SHOTS AND COVID-19 VACCINES ON NOVEMBER 6, 2021 - 10-25-YYYY -... - October 26th, 2021
- Male Infertility Could Be Treated With Monkey Cells; New Study Shows How These Animals Could Help Address the Condition - Science Times - October 26th, 2021
- Citius Pharmaceuticals to Host Key Opinion Leader Webcast on the Compelling Need to Salvage Central Venous Catheters in CLABSI Patients - Yahoo... - October 26th, 2021
- New findings may help widen therapeutic interventions for B-cell acute lymphoblastic leukemia - News-Medical.Net - October 25th, 2021
- Getting to Know Kate Roth at Beacon Integrative Medical Center in Rexburg - East Idaho News - October 25th, 2021
- Global Cell Therapy Market Report 2021-2028 - Growing Adoption of Regenerative Medicine & Introduction of Novel Platforms and Technologies -... - October 25th, 2021
- Vertex reports positive results for first patient in Type 1 diabetes trial - BetaBoston - October 23rd, 2021
- Morris receives grant for stem cell research - The Source - Washington University Record - October 23rd, 2021
- Vertex moves ahead with its bid to develop a curative treatment for type 1 diabetes - PMLiVE - October 23rd, 2021
- McLaughlin Research Institute receives $5 million gift to support neurology studies - Great Falls Tribune - October 23rd, 2021
- AML medication and treatment: What to know - Medical News Today - October 23rd, 2021
- U S Stem Cell : USRM to Focus on Animal Health and Lead Pet-Care Innovation - Marketscreener.com - October 19th, 2021
- Opinion: Why Colin Powell's death should not be framed as the death of a vaccinated person - Poynter - October 19th, 2021
- Quris combines AI with patient on a chip to speed drug development and reduce animal testing - TechCrunch - October 19th, 2021
- Dr. Helen Heslop elected to the National Academy of Medicine - Baylor College of Medicine News - October 19th, 2021
- Researchers report long-lasting effects of gene therapy in children with deadly immune disorder - News-Medical.Net - October 19th, 2021
- Coronavirus: How does misinformation spread, and how can we stop it? - The Jerusalem Post - October 17th, 2021
- Dr. Kahl on the Potential Utility of Frontline CAR T-Cell Therapy in MCL - OncLive - October 17th, 2021
- FDA Approves Genentech's Tecentriq as Adjuvant Treatment for Certain People With Early Non-Small Cell Lung Cancer - Business Wire - October 17th, 2021
- Global Stem Cell and Primary Cell Culture Medium Market 2021 Trends and Leading Players Analysis 2027 Merck, STEMCELL Technologies, Irvinesci, Cell... - October 15th, 2021
- Dr. Erba on the Evolution of Treatment in MCL - OncLive - October 15th, 2021
- After no stem cell donors stepped up to saved her son, mom continues to help others facing the same challenge - Chicago Tribune - October 15th, 2021
- International ZIM Network: SmartMed - Regenerative Solutions for the Therapies of Tomorrow - Business Wire - October 15th, 2021
- Are 'robot massages' the future of muscle repair? - Medical News Today - October 15th, 2021
- What the FDA Panel's Moderna Booster Shot Vote Means and What's Next - NBC Chicago - October 15th, 2021
- Phase 2 Clinical Trial Data of NurOwn in Progressive MS Will Be Presented at the 37th Congress of the European Committee for Treatment and Research in... - October 15th, 2021
- R3 Stem Cell & Exosome Therapy: Joint & Back Pain, Avoid ... - October 13th, 2021
- Stem Cell PhD Program | Institute for Stem Cell Biology ... - October 13th, 2021
- New stem cell identified by Sanford Burnham Prebys researchers offers hope to people with rare liver disease - Newswise - October 13th, 2021
- Repurposed Drug Reverses Signs of Alzheimers in Mice, Human Cells - The Scientist - October 13th, 2021
- Bone Therapeutics appoints Scientific Advisory Board for iMSC cell and gene therapy platform development - StreetInsider.com - October 13th, 2021
- What the latest COVID research says about breakthrough cases and transmission : Shots - Health News - NPR - October 13th, 2021
- HNF collaborates with Rarebase on a Drug Discovery Platform to develop treatments for Charcot-Marie-Tooth (CMT) - PRNewswire - October 13th, 2021
- Autologous HSCT Continues to Show Sustained Benefit in MCL, But Targeted Therapies May Challenge its Role as Standard Frontline Treatment -... - October 13th, 2021
- Bartolo Coln, Winner Of The Cy Young, Wins Lawsuit In Case Of Stem Cell Treatment To Which He Was Subjected Before His Return To The Major Leagues. -... - October 11th, 2021
- The Impact Of Market Restrictions On The US Stem Cell Biomaterials Market - Med Device Online - October 11th, 2021
- Vitro Biopharma Inc. July 31st 2021; 3rd Quarter ended Financial Results of Operations and Shareholder Letter. - Yahoo Finance - October 11th, 2021
- Top US Leukemia Experts from Academia, Industry and Public Sector Coming Together at Acute Myeloid Leukemia Conference on October 22 - OncLive - October 11th, 2021
- Precision medicine data dive shows water pill may be viable to test as Alzheimer's treatment - National Institutes of Health - October 11th, 2021
- Treating Early Relapse in Follicular Lymphoma - Targeted Oncology - October 11th, 2021
- Humans and Chimpanzees Use a Part of Their DNA in Different Ways - Technology Networks - October 11th, 2021
- A stem cell treatment for MS offers some patients hope. But is it hope that will last? - WHYY - October 9th, 2021
- CAR T Offer New Treatment Option for Non-Hodgkin Lymphoma - Targeted Oncology - October 9th, 2021
- FDA Advisory Committee Recommends Maribavir to Treat Cytomegalovirus CMV Infection and Disease - Contagionlive.com - October 9th, 2021
- What surgeons are saying about regenerative medicine in 2021 - Becker's Orthopedic & Spine - October 9th, 2021
- Study illuminates how BRD4 protein directs the spatial organization of DNA within cell nucleus - News-Medical.net - October 9th, 2021
- Cellular Therapy Strategies Offer the Prospect of Deep Remissions for Multiple Myeloma - OncLive - October 9th, 2021
- Anti-CD47 Therapy and Other New Approaches to the Treatment of Myelodysplastic - Targeted Oncology - October 9th, 2021
- ViaCyte to Present at Alliance for Regenerative Medicine Cell & Gene Meeting on the Mesa - PRNewswire - October 7th, 2021
- Seattle Stem Cell Therapy Clinic - Seattle Sports Medicine ... - October 7th, 2021
- StemExpress Partners with the Alliance for Regenerative Medicine to Provide COVID-19 Testing for the Cell and Gene Meeting on the Mesa - PRNewswire - October 7th, 2021
- New Stem Cell Approach Through Using Wavelength Laser Might have Discovered Why Humans Lose Hair - Tech Times - October 5th, 2021
- Faster healing of wounds can decrease pain and suffering and save lives - WMTV - NBC15 - October 5th, 2021
- Losing Your Hair? You Might Blame the Great Stem Cell Escape. - The New York Times - October 5th, 2021
- Northwesterns SPORE has made advances in understanding the genetic basis of glioblastoma - News-Medical.Net - October 5th, 2021
- NextCure Announces New Appointments to its Board of Directors - GlobeNewswire - October 5th, 2021
- Therapy and Prevention Strategies for Myocardial Infarction | IJN - Dove Medical Press - October 3rd, 2021
- Lack of awareness about blood stem cell donation is one of the leading causes for low number of donors in In.. - ETHealthworld.com - October 3rd, 2021
- Advanced technique offers new insights about the dynamics of gliomas - News-Medical.net - October 3rd, 2021
- "Stem cell-based therapeutics poised to become mainstream option - BSA bureau - October 2nd, 2021
- The stem cell revolution isnt what you think it is - New Scientist News - October 2nd, 2021
- Stem cell agency gives out $2 million a minute - Capitol Weekly - October 2nd, 2021
- Researching the Safety and Effectiveness of Stem Cells to Treat 'Long Covid' - Entrepreneur - October 2nd, 2021
- United States Regenerative Medicine Markets to 2026: Focus on Cell Therapies, Gene Therapies, Progenitor & Stem Cell Therapies, Tissue Engineered... - October 2nd, 2021
- U.S. FDA Approves Kite's Tecartus as the First and Only Car T for Adults With Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia - Business... - October 2nd, 2021
- Omeros Provides Regulatory Update on Biologics License Application for Narsoplimab in the Treatment of HSCT-TMA - Business Wire - October 2nd, 2021
- Stem Cell Umbilical Cord Blood Market in North America 2021 Sees Growth Due to Rising Spending Capacity and Suitable Payment Plans - PRNewswire - October 2nd, 2021
- BrainStorm to Present Phase 2 Progressive MS Study Results in Oral Presentation at 37th Congress of ECTRIMS - BioSpace - October 2nd, 2021
- Macomics Announces New Hires that Expands its Macrophage-based Drug Discovery R&D Team - BioSpace - October 2nd, 2021
- Stanford neuroscientist's 'assembloids' pave the way for innovative brain research - Scope - October 2nd, 2021
- At the crossroads of reproductive and regenerative medicine: new opportunities for preserving and restoring fertility - ESHRE - September 25th, 2021
- Doctors Debate: Do CAR T Cells and Transplantation Both Have a Place in Aggressive B-Cell Lymphoma Treatment? - Targeted Oncology - September 25th, 2021
- Global Stem Cell Alopecia Treatment Market 2021 Development Status,Industry Insights and Forecast Research Report 2027 Stillwater Current -... - September 25th, 2021
- AML vs. ALL: Differences in symptoms, diagnosis, and survival - Medical News Today - September 25th, 2021
- New gene therapies may soon treat dozens of rare diseases - American Society for Biochemistry and Molecular Biology - September 25th, 2021
- BioRestorative Therapies Receives Notice of Allowance for Patent Application in Israel for its Metabolic Program - GlobeNewswire - September 25th, 2021