Cell Replacement Therapy For Parkinsons Disease And The …
By LizaAVILA
The following was written withProf. Gerold Riempp, a professor of information systems who was diagnosed with Parkinsons disease 16 years ago at age 36. He is co-founder of a charitable organization in Germany that supports the development of therapies that aim to cure PD.
The idea behind cell replacement therapy(CRT) for PD is pretty simple: lack of mobility in PD is the result of the dysfunction and death of a specific kind of cell in the midbrain. While there are a few other things that go wrong in PD, the progressive loss of motor skills is the biggest problem most diagnosed face. Since we are reasonably sure that this lack of mobility results from the impairment and death of dopamine producing cells in an area of the midbrain called the substantia nigra,why not try to replace those cells?
A group of iPS cells grown from human skin tissue at Osaka University
Replacing those cells is one of three core problems that each person diagnosed with PD needs to address. They are:
1. Keeping remaining cells healthyOnce diagnosed, most people have already lost production of 50-80% of dopamine in their midbrain. The problem then is to stop further disease progression by figuring out how to get rid of everything that might be harming the remaining 20-50% of cells while giving their body everything it needs to keep those cells alive and active.
2. Clearing clogged cellsOf those 50-80% of non-dopamine producing cells, a portion are still alive, they are just not doing their job, producing dopamine. This impairment is a result of a range of interrelated factors that harm the cells and eventually lead to their death. Most researchers believe the problem can be boiled down to the clumping of a misfolded protein called alpha-synuclein. Many different methods are being tried in labs around the world to clear these clumps and stop more from accumulating. But this might only be part of the story since a wide variety of other factors also lead to cell death.
3. Replacing dead cellsThen we come to what to do about all of those dead cells. A couple of different options are being considered to get the brain tostimulate the production of new neurons orreplace the function of dead ones. However, the most promising therapy being developed is stem cell therapy, now commonly referred to as cell replacement therapy. It works by placing new dopamine producing neurons into the part of the brain where the dead neurons used to release dopamine.
If a patient manages to address problems one and two they might have no need for CRT. The reason for this is that he or she can likely rescue a considerable portion of the damaged but still living cells and thereby bring dopamine production back to a level that allows for normal movement. CRT will generally be for people who have had PD for a longer time and whose remaining healthy cells plus the rescued ones together are not capable of providing enough dopamine.
The late 80s and 90s saw a number of CRT trials for Parkinsons disease with mixed results. But we nowhave a much better understanding of what kind of cells to use, how to culture and store those cells, how to implant them, and who this therapy would be best for.
We also now have iPS cells (induced pluripotent stem cells). Discovered in 2006, these are cells that have been chemically reprogrammed, usually from adult skin tissue, back into pluripotent stem cells. (Pluripotent means they are capable of becoming almost any cell in the body). Using these cells for transplantation has two major advantages. One, it eliminates the need for potentially harmful immuno-suppressors. Two, it has none of the ethical issues that come with using fetal stem cells. But iPS cells are much more expensive and technically difficult to produce.
Despite all the progress made, cell replacement therapy is still very controversial and fraught with all sorts of technical issues. Luckily, CRT for PD is one of the only fields of medical science where the top labs around the world are cooperating with each other. An international consortium of labs has come together under a name that sounds like it was ripped out of a Marvel comic, the GForce-PD. Each lab in the GForce-PD aims to bring CRT for PD to clinical trial within the next few years.
Infographic made by PhD neuroscientist Kayleen Schreiber at kayleenschreiber.com
The GForce-PD
New York City Run by Dr. Lorenz Studer out of the Rockefeller research labs in New York City. Dr. Studer pioneered many of the reprogramming techniques being used around the world to convert pluripotent stem cells into dopamine producing neurons. His lab wasrecently announced to be part of a huge funding initiative from Bayer Pharmaceuticals to help speed up development of CRT. Studers lab is aiming to start transplantation of embryonic stem cells in human trials in early 2018.
Kyoto, Japan Dr. Jun Takahashis lab in Kyoto is working on producing several iPS lines for the Japanese population. One advantage they have is the relative homogeneity of Japanese people allows them to use a dozen or so iPS lines for almost everyone in the country. The lab recently made headlines with results from monkey trials that showed human iPS cells graft safely, with no signs of malignant growth, two years after transplantation.
Cambridge, England Dr. Roger Barkers lab has been working on cell replacement therapy for Parkinsons disease for a number of years through the Transeuro project. His lab is pushing forward with more embryonic stem cell transplantations expected to begin in 2020. They also work very closely with the team in Sweden.
Lund, Sweden The lab in Lund has been working on CRT for PD since the 80s and has been part of a number of human trials. The lab is now run by Dr. Malin Parmar whose team has also pioneered many of the techniques used in direct programming that will one day allow researchers to skip the stem cell phase all together and produce dopamine cells directly in the brain.
San Diego, California The team is moving rapidly towards iPS cell transplantation under Dr. Jeanne Loring at the Scripps research center. They are the only lab that uses patients own cells for transplantation. Another unique feature of this lab is that it has been a community funded initiative under theSummit For Stem Cellsfoundation.
(Dr. Roger Barker talking about CRT for PD)
Though there is a lot of excitement building around cell replacement therapy, we need to proceed carefully. The field has potential for setbacks from some of the less rigorous trials being conducted in places like Australia and China where regulatory standards are more lax. Researchers in these areas are already going ahead with trials that do not meet the standards set by the GForce-PD. These have the potential to put a black-eye on all cell replacement therapies.
Also, producing pure batches of dopamine neurons is still a highly technical process that only a few labs in the world are capable of doing safely and effectively. Thankfully a few other labs around the world are joining the efforts of the GForce-PD, such as Dr. Tilo Kunaths lab in Edinburgh, which is working on techniques to better differentiate and characterize the cell lines used for transplantation.
(The pictures above show human embryonic stem cells being differentiated into dopamine cells at days 2, 4 and 7. Courtesy of Dr. Tilo Kunaths lab at the University of Edinburgh)
The Future of Cell Replacement Therapy
These therapies being developed for Parkinsons disease will, in essence, be version 1.0 of CRT. Clinical trials are set to begin next year and the therapy is expected to be widely available to people diagnosed with Parkinsons disease within the next 5-10 years.
Version 2.0 will be CRISPR-modified, disease resistant grafts, with genetic switches to modulate dopamine production and graft size.
Version 3.0 will make use of an emerging field called in vivo direct programming where viruses are inserted into the brain and transform other existing cells into dopamine producing cells.
(Edit: Credit to Dr. Tilo Kunath for correcting versions 2.0 and 3.0)
Dopamine neurons grown from iPS cells at 40 times magnification, from the Gladstone Institute
CRT for PD is one of the most exciting areas of research on the planet. It is a powerful demonstration of the progress we as a species have made in our attempt to gain mastery over the forces of biology.It has the potential to improve the lives of the millions living with PD, and the millions yet to be diagnosed. Once the transplanted cells have connected with their surroundings and start delivering dopamine to the right places, it should allow patients to gradually reduce their medication. Being able to move normally and not deal with the side effects of all the drugs and other therapies is what PD patients around the world are dreaming of.
Click here for more information on the future of cell replacement therapy for Parkinsons disease and the work of the GForce-PD.
And if you want to be part of bringing CRT to the clinic you can do so by supporting organizations like Summit For Stem Cells.
Like Loading...
Related
Originally posted here:
Cell Replacement Therapy For Parkinsons Disease And The ...
- 001 Ying Liu discusses IPS cell therapy for ALS [Last Updated On: August 6th, 2011] [Originally Added On: August 6th, 2011]
- 002 Jeanne Loring talks about stem cells, part 2 [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- 003 Embryonic Stem Cells From Skin: Making Old Cells Young [Last Updated On: September 5th, 2011] [Originally Added On: September 5th, 2011]
- 004 IPs cells Part3 [Last Updated On: September 6th, 2011] [Originally Added On: September 6th, 2011]
- 005 IPs cells Part 2 [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- 006 A Century of Stem Cells - Johns Hopkins Medicine [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- 007 Stem Cell Implications for ALS (Amyotrophic Lateral Sclerosis) [Last Updated On: September 7th, 2011] [Originally Added On: September 7th, 2011]
- 008 Myelin Repair Foundation on Stem Cell Research [Last Updated On: September 9th, 2011] [Originally Added On: September 9th, 2011]
- 009 IPs Cells Part 4 [Last Updated On: September 11th, 2011] [Originally Added On: September 11th, 2011]
- 010 National Medical Report [Last Updated On: September 13th, 2011] [Originally Added On: September 13th, 2011]
- 011 IPs cells Part 1 [Last Updated On: September 15th, 2011] [Originally Added On: September 15th, 2011]
- 012 iPS Stem Cell-Based Treatment of Epidermolysis Bullosa [Last Updated On: September 16th, 2011] [Originally Added On: September 16th, 2011]
- 013 Jeanne Loring talks about stem cells, part 1 [Last Updated On: September 16th, 2011] [Originally Added On: September 16th, 2011]
- 014 Kristopher Nazor 2 [Last Updated On: September 16th, 2011] [Originally Added On: September 16th, 2011]
- 015 Andalusian Stem Cell Bank [Last Updated On: September 19th, 2011] [Originally Added On: September 19th, 2011]
- 016 Cellular Reprogramming Stem Cell Domain Name For Sale! - CellularReprogramming.com [Last Updated On: September 20th, 2011] [Originally Added On: September 20th, 2011]
- 017 Dr. Oz to Oprah and Michael J Fox: "The stem cell debate is dead." [Last Updated On: September 22nd, 2011] [Originally Added On: September 22nd, 2011]
- 018 Manning, Owens Try Stem Cell Therapy [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 019 Jeanne Loring talks about stem cells, part 3 [Last Updated On: October 5th, 2011] [Originally Added On: October 5th, 2011]
- 020 Epidermolysis Bullosa: Corrected iPS Stem Cell-Based Therapy - Video [Last Updated On: October 13th, 2011] [Originally Added On: October 13th, 2011]
- 021 Introduction to Stem Cells - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- 022 Parkinson's Disease: Progress and Promise in Stem Cell Research - Video [Last Updated On: October 14th, 2011] [Originally Added On: October 14th, 2011]
- 023 stem cell research - Video [Last Updated On: December 7th, 2011] [Originally Added On: December 7th, 2011]
- 024 Ian Wilmut discusses stem cell and direct cellular transformation therapy - Video [Last Updated On: December 8th, 2011] [Originally Added On: December 8th, 2011]
- 025 Jeff Bluestone: Immune rejection of stem cell transplants - Video [Last Updated On: December 8th, 2011] [Originally Added On: December 8th, 2011]
- 026 Advances in Stem Cell Research: Shinya Yamanaka - Video [Last Updated On: December 11th, 2011] [Originally Added On: December 11th, 2011]
- 027 2011 Summit: Stem Cells, Reprogramming and Personalized Medicine, Rudolf Jaenisch, MD - Video [Last Updated On: December 14th, 2011] [Originally Added On: December 14th, 2011]
- 028 Parkinson's Disease: Advancing Stem Cell Therapies - 2011 CIRM Grantee Meeting - Video [Last Updated On: January 20th, 2012] [Originally Added On: January 20th, 2012]
- 029 Professor Alan Trounson - World focus on stem cell research - Video [Last Updated On: January 27th, 2012] [Originally Added On: January 27th, 2012]
- 030 Stanford scientists turn skin cells into neural precusors, bypassing stem-cell stage [Last Updated On: January 31st, 2012] [Originally Added On: January 31st, 2012]
- 031 Researchers turn skin cells into neural precusors, bypassing stem-cell stage [Last Updated On: January 31st, 2012] [Originally Added On: January 31st, 2012]
- 032 “Wide-ranging applications for pluripotent stem cells” [Last Updated On: February 2nd, 2012] [Originally Added On: February 2nd, 2012]
- 033 Radiation treatment transforms breast cancer cells into cancer stem cells [Last Updated On: February 14th, 2012] [Originally Added On: February 14th, 2012]
- 034 Radiation Treatment Generates Cancer Stem Cells from Less Aggressive Breast Cancer Cells [Last Updated On: February 14th, 2012] [Originally Added On: February 14th, 2012]
- 035 Radiation treatment generates cancer stem cells from less aggressive breast cancer cells, study suggests [Last Updated On: February 14th, 2012] [Originally Added On: February 14th, 2012]
- 036 Life Technologies Scientist Uma Lakshmipathy presents, "Solving Challenges in the Generation of Induced Pluripotent ... [Last Updated On: February 14th, 2012] [Originally Added On: February 14th, 2012]
- 037 Radiation therapy transforms breast cancer cells into cancer stem cells [Last Updated On: February 14th, 2012] [Originally Added On: February 14th, 2012]
- 038 Research and Markets: Primary and Stem Cells: Gene Transfer Technologies and Applications [Last Updated On: February 15th, 2012] [Originally Added On: February 15th, 2012]
- 039 Horizon in new super-cell elite [Last Updated On: February 16th, 2012] [Originally Added On: February 16th, 2012]
- 040 Presentations at the Society of Toxicology Annual Meeting Demonstrate Superior Predictivity of Cellular Dynamics ... [Last Updated On: March 8th, 2012] [Originally Added On: March 8th, 2012]
- 041 New approach to treating type 1 diabetes? Transforming gut cells into insulin factories [Last Updated On: March 12th, 2012] [Originally Added On: March 12th, 2012]
- 042 Gut cells transformed into insulin factories 'could help to treat type I diabetes' [Last Updated On: March 12th, 2012] [Originally Added On: March 12th, 2012]
- 043 A new approach to treating type I diabetes? Gut cells transformed into insulin factories [Last Updated On: March 12th, 2012] [Originally Added On: March 12th, 2012]
- 044 Columbia Researchers Find Potential Role for Gut Cells in Treating Type I Diabetes [Last Updated On: March 12th, 2012] [Originally Added On: March 12th, 2012]
- 045 Study demonstrates cells can acquire new functions through transcriptional regulatory network [Last Updated On: March 14th, 2012] [Originally Added On: March 14th, 2012]
- 046 Gut Cells Turned To Insulin Factories - New Type l Diabetes Treatment [Last Updated On: March 14th, 2012] [Originally Added On: March 14th, 2012]
- 047 Cellular Dynamics Expands Distribution Agreement with iPS Academia Japan, Inc. to Include Distribution of iCell ... [Last Updated On: March 28th, 2012] [Originally Added On: March 28th, 2012]
- 048 :: 20, Apr 2012 :: IBN DISCOVERS HUMAN NEURAL STEM CELLS WITH TUMOR TARGETING ABILITY – A PROMISING DISCOVERY FOR ... [Last Updated On: April 22nd, 2012] [Originally Added On: April 22nd, 2012]
- 049 Human neural stem cells with tumor targeting ability discovered [Last Updated On: April 22nd, 2012] [Originally Added On: April 22nd, 2012]
- 050 IBN Discovers Human Neural Stem Cells, Promising Discovery For Breast Cancer Therapy [Last Updated On: April 22nd, 2012] [Originally Added On: April 22nd, 2012]
- 051 IBN Discovers Human Neural Stem Cells with Tumor Targeting Ability - A Promising Discovery for Breast Cancer Therapy [Last Updated On: April 22nd, 2012] [Originally Added On: April 22nd, 2012]
- 052 VistaGen Secures Key U.S. Patent Covering Stem Cell Technology Methods Used to Test Drug Candidates for Liver Toxicity [Last Updated On: April 25th, 2012] [Originally Added On: April 25th, 2012]
- 053 Improved adult-derived human stem cells have fewer genetic changes than expected [Last Updated On: May 2nd, 2012] [Originally Added On: May 2nd, 2012]
- 054 Researchers restore neuron function to brains damaged by Huntington's disease [Last Updated On: May 31st, 2012] [Originally Added On: May 31st, 2012]
- 055 Cellular Dynamics Launches MyCell™ Services [Last Updated On: June 7th, 2012] [Originally Added On: June 7th, 2012]
- 056 Fate Therapeutics And BD Biosciences Launch BD™ SMC4 To Improve Cellular Reprogramming And IPS Cell Culture Applications [Last Updated On: June 12th, 2012] [Originally Added On: June 12th, 2012]
- 057 Life Technologies and Cellular Dynamics International Partner for Global Commercialization of Novel Stem Cell ... [Last Updated On: June 13th, 2012] [Originally Added On: June 13th, 2012]
- 058 LIFE Focuses on Stem Cell Research - Analyst Blog [Last Updated On: June 20th, 2012] [Originally Added On: June 20th, 2012]
- 059 International Stem Cell Corp Granted Key Patent for Liver Disease Program [Last Updated On: September 30th, 2012] [Originally Added On: September 30th, 2012]
- 060 NeuroGeneration Recruits Top Scientist To Direct New Division of Biotherapeutics and Drug Discovery In La Jolla, CA [Last Updated On: October 5th, 2012] [Originally Added On: October 5th, 2012]
- 061 FRC Supports Alliance Defending Freedom, Jubilee Campaign Cert Petition to Supreme Court on Stem Cell Funding [Last Updated On: October 11th, 2012] [Originally Added On: October 11th, 2012]
- 062 10/11/2012 10:05 JAPAN Nobel Prize for Yamanaka, scientific research and ethics must go hand in hand [Last Updated On: October 11th, 2012] [Originally Added On: October 11th, 2012]
- 063 Read in [Last Updated On: October 12th, 2012] [Originally Added On: October 12th, 2012]
- 064 Induced pluripotent stem cell - Wikipedia, the free encyclopedia [Last Updated On: November 3rd, 2013] [Originally Added On: November 3rd, 2013]
- 065 What are induced pluripotent stem cells or iPS cells? - Stem Cells ... [Last Updated On: November 3rd, 2013] [Originally Added On: November 3rd, 2013]
- 066 Stem Cell Definitions | California's Stem Cell Agency [Last Updated On: November 3rd, 2013] [Originally Added On: November 3rd, 2013]
- 067 iPSCTherapy.com: Induced Pluripotent Stem Cell therapy Information ... [Last Updated On: November 8th, 2013] [Originally Added On: November 8th, 2013]
- 068 Human muscle stem cell therapy gets help from zebrafish [Last Updated On: November 8th, 2013] [Originally Added On: November 8th, 2013]
- 069 Induced pluripotent stem cell therapy - Wikipedia, the free ... [Last Updated On: November 8th, 2013] [Originally Added On: November 8th, 2013]
- 070 IPS Cell Therapy - Genetherapy [Last Updated On: November 8th, 2013] [Originally Added On: November 8th, 2013]
- 071 MD Supervised Stem Cell Therapy [Last Updated On: November 9th, 2013] [Originally Added On: November 9th, 2013]
- 072 Stem Cell Therapy for Neuromuscular Diseases | InTechOpen [Last Updated On: November 23rd, 2013] [Originally Added On: November 23rd, 2013]
- 073 Combining Stem Cell Therapy with Gene Therapy | Boston ... [Last Updated On: November 25th, 2013] [Originally Added On: November 25th, 2013]
- 074 Biomanufacturing center takes central role in developing stem ... [Last Updated On: December 4th, 2013] [Originally Added On: December 4th, 2013]
- 075 Stem Cell Quick Reference - Learn Genetics [Last Updated On: December 6th, 2013] [Originally Added On: December 6th, 2013]
- 076 Induced Pluripotent Stem Cells (iPS) from Human Skin: Probable ... [Last Updated On: December 6th, 2013] [Originally Added On: December 6th, 2013]
- 077 'Something positive for humankind': Girls lend cells to genetic study [Last Updated On: December 13th, 2013] [Originally Added On: December 13th, 2013]
- 078 Stem cell science: Can two girls help change the face of medicine? [Last Updated On: December 13th, 2013] [Originally Added On: December 13th, 2013]
- 079 Okyanos Heart Institute CEO Matt Feshbach Congratulates Japan’s Legislators On Stem Cell Bill And Global Regulatory ... [Last Updated On: December 13th, 2013] [Originally Added On: December 13th, 2013]
- 080 Stem cells for Parkinson's getting ready for clinic [Last Updated On: December 13th, 2013] [Originally Added On: December 13th, 2013]
