Autologous induced pluripotent stem cell-derived dopamine neuron replacement therapy for Parkinson's disease
Why treat Parkinson’s disease with cell therapy?
Parkinson’s disease is an ideal candidate for cell replacement therapy because it is caused by the loss of a single cell type in a specific part of the brain.
Parkinson’s disease is caused by loss of dopamine neurons
- >50% of dopamine neurons are gone by diagnosis
- Parkinson’s disease is the second most common neurological disorder
- 10 million patients worldwide
- Drug therapy (L-DOPA) cannot treat the disease long-term.
Proof of concept: Fetal tissue grafts
In the late 1990s and early 2000s, more than 300 people with PD were transplanted with brain tissue from 6-10 week old fetuses.
The results were variable, but in some cases symptoms were reversed and sustained for more than 20 years.
Issues related to fetal tissue transplants:
- Insufficient tissue
- Highly variable tissue
- Cannot comprehensively analyze tissue before transplant
- Graft-induced dyskinesias
Freed, CR et. al. New Engl. J. of Med. 344(10), 710-719 (2001); Grealish, et. al. Cell Stem Cell 15, 653-665 (2014); Olanow CW, et. al. Ann Neurol. 54:403-414 (2003); Wen Li, et. al. PNAS 113:6544-6549 (2016)
Induced pluripotent stem cells (iPSCs) for neuron replacement therapy
Pluripotent stem cells
Autologous iPSC-derived dopamine neuron replacement therapy uses iPSCs
- Can be made from patients
- Do not require immune suppression – AUTOLOGOUS (as opposed to allogeneic)
- Unlimited source of cells
- Ability to differentiate into any cell type
- Can control their fate in culture to dopamine neurons
- Amenable to comprehensive quality control
(See “Stem Cells 101” for more info on iPSCs)
- Skin punch biopsies are taken from Parkinson’s disease patients to isolate skin cells
- Skin cells are reprogrammed to make iPSCs that are immune matched (autologous) to the patient
- The iPSCs are differentiated into dopamine producing neurons
- The dopamine producing neurons are transplanted back into the patient to reset the clock on Parkinson’s disease
Autologous vs. Allogeneic Stem Cell Therapy
International stem cell therapies for Parkinson's Disease
*Note that the Summit for Stem Cell PD Trial mentioned in the table above has been transferred to Aspen Neuroscience (see below for more info)
Summit’s role in the development of the autologous iPSC-derived dopamine neuron replacement therapy
- Summit was founded in 2011 as a grass roots volunteer organization comprised of patients, medical and scientific professionals and community members with a desire to raise funds for a stem cell-based solution to Parkinson’s disease.
- Summit paired with Drs Jeanne Loring and Andres Bratt-Leal, then located at the Scripps Research Institute in La Jolla, CA to develop this stem cell based therapy.
- Over the years, Summit raised millions of dollars to support this project.
- As the project progressed, it became clear that in order for the project to be successful, a private sector biotech company would have to be built in order to raise the type of funds that would be necessary to bring the project from bench to bedside.
- In 2018, Aspen Neuroscience was created to bring the autologous iPSC-derived dopamine neuron replacement therapy to the Parkinson’s patient population and now the project is on an accelerated path toward FDA-approved clinical trials.
- Summit continues with passionate dedication to advocate for persons living with Parkinson’s and other neurodegenerative diseases.
- We update patients about the autologous iPSC-derived dopamine neuron replacement therapy, provide financial assistance to patients who want to participate in the trial and fund evidence based regenerative medical therapies for Parkinson’s and other neurodegenerative diseases.