A total of six participants will be included in the Phase 1 trial that will track the patients for 12 months and beyond to determine the safety of the procedure and monitor for any improvements in Parkinson’s disease. Following the first 6 patients transplanted in the Phase 1 study, the researchers hope to expand and recruit more patients as part of Phase 2A study.

This novel therapeutic approach for treating Parkinson’s disease incorporates the use of stem cells derived from a patient’s own blood that had been converted into induced pluripotent stem cells (iPSCs). These cells are then reprogrammed to turn into specific midbrain dopaminergic neurons ready for transplantation. The autologous transplantation approach of using a person’s own cells circumvents the requirement for immunosuppressive treatments, which are necessary when cells from other donors are used.

Cell replacement for Parkinson’s disease replaces the dopamine neurons lost to degeneration and can restore dopaminergic function in the brain, providing a completely new treatment modality compared to the currently available treatments. The NRI’s founding director, Ole Isacson, Dr Med Sci, who is also a professor of neurology (neuroscience) at Harvard Medical School and Mass General Brigham, has pioneered work in cell therapy for Parkinson’s disease over the past 30 years and laid the foundation for this clinical trial.

“Seeing this transformational new patient cell-based replacement of their own dopamine neurons come to fruition — from the very basic science breakthroughs in our lab to be completely translated into a clinical application for patient’s suffering from Parkinson’s disease — is very gratifying,” said Isacson. “We believe this approach may open up a new treatment paradigm and lead to the development of many additional cell therapies to restore damaged brain systems and replace degenerated brain cells in other diseases.”

Under Isacson’s leadership, the NRI at McLean has developed and patented autologous cell-based restoration in Parkinson’s disease with a pioneering preclinical publication in 2002 using stem cells and the first preclinical demonstration of effective human iPS cell-derived dopamine neuron use in 2010. In 2015, the NRI team, led by Isacson and Penny Hallett, PhD, co-director of the NRI at McLean and associate professor of psychiatry at Harvard Medical School, provided the first evidence of long-term safety and benefits of autologous stem cell therapy in a highly relevant Parkinson’s disease non-human primate animal model.

The NRI received official authorization from the U.S. Food and Drug Administration (FDA) on August 23, 2023, approving its Investigational New Drug (IND) application for a phase 1 clinical trial to test this unique, autologous dopamine neuron cell therapy.

Following this FDA approval for the phase 1 clinical trial, the NRI’s innovative preclinical work was translated into the clinic with the first patient treated on September 9, 2024. This collaboration includes NRI investigators James Schumacher, MD, and Oliver Cooper, PhD, and colleagues in the Neurology (Michael Hayes, MD) and Neurosurgery (John Rolston, MD, PhD, principal investigator of the Phase 1 trial) Departments at Brigham and Women’s Hospital. Isacson is not directly involved in the clinical trial because he is the innovator patent holder of the technology and also a co-founder of Oryon Cell Therapies, which has the license to this technology. The trial is directed by Hallett and colleagues within the Mass General Brigham healthcare system and its Harvard Medical School-affiliated institutions.

“It is extraordinary to witness that investigators at our institution can bring new treatments to patients through the entire process of laboratory “bench to bedside,” and it inspires many investigators to similarly pursue their scientific and medical insights to reach patients in need,” said Kerry Ressler MD, PhD, chief scientific officer at McLean Hospital.

The Phase 1 open-label clinical trial will be the first such trial to test blood-derived autologous iPSC-derived dopamine neurons in patients with Parkinson’s disease and is funded by the National Institute of Health’s National Institute of Neurological Disorders and Stroke (NINDS). The NINDS awarded the highly competitive Cooperative Research to Enable and Advance Translational Enterprises for Biologics (CREATE Bio) grant for this work in 2020.

People seeking more information in the trial can email: @bwh.harvard.edu” title=”mailto:neurosurgerycrc@bwh.harvard.edu”>neurosurgerycrc@bwh.harvard.edu

For More Information:

• McLean Hospital Receives Coveted NIH Grant to Clinically Study Autologous Stem Cell Therapy for Parkinson’s Disease
• Patient-derived stem cells could improve drug research for Parkinson’s

Funding: The study was supported by a NINDS CREATE Bio grant (U01NS109463).

The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Disclosure:Isacson has co-founded a company (Oryon Cell Therapies) which has licensed the patents and know-how for developing autologous cell therapies for Parkinson’s disease. Isacson’s interests were reviewed and are managed by McLean Hospital and Mass General Brigham in accordance with their conflict of interest polices.

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About Mass General Brigham

Mass General Brigham is an integrated academic health care system, uniting great minds to solve the hardest problems in medicine for our communities and the world. Mass General Brigham connects a full continuum of care across a system of academic medical centers, community and specialty hospitals, a health insurance plan, physician networks, community health centers, home care, and long-term care services. Mass General Brigham is a nonprofit organization committed to patient care, research, teaching, and service to the community. In addition, Mass General Brigham is one of the nation’s leading biomedical research organizations with several Harvard Medical School teaching hospitals. For more information, please visit massgeneralbrigham.org.

Manganese, selenium, magnesium and copper are among the essential metals important for a healthy body because their anti-oxidation and anti-inflammatory properties may help protect against cardiovascular disease. Previous research has found that higher levels of manganese were associated with a lower risk of preeclampsia (high blood pressure during pregnancy). However, it is not known whether higher levels of essential metals during pregnancy may influence the risk of developing high blood pressure later in life. Additionally, chronic exposure to the non-essential metals lead, cadmium and arsenic is associated with an increased risk of cardiovascular disease, according to the Association’s 2023 scientific statement “Contaminant Metals as Cardiovascular Risk Factors.”

“People are constantly exposed to heavy metals and trace elements, and much research has shown that exposure to those metals and elements may have an impact on cardiovascular health, especially hypertension,” said lead study author Mingyu Zhang, Ph.D., M.H.S., an epidemiologist and instructor in medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, both in Boston. “In our study, we wanted to examine how levels of essential metals and elements during pregnancy may affect blood pressure and hypertension risk in midlife.”

The researchers analyzed data from Project Viva, an ongoing, long-term study that began in 1999 of women and their children who live in eastern Massachusetts. Nearly 500 women enrolled in the study during early pregnancy, between 1999 and 2002. Researchers measured concentrations of non-essential metals (arsenic, barium, cadmium, cesium, mercury and lead), essential minerals (copper, magnesium, manganese, selenium and zinc), folate and vitamin B12 in blood samples collected during study enrollment.

After nearly twenty years of follow-up, researchers conducted a “midlife” study visit between 2017 and 2021 with the same study participants, who were now at a median age of 51.2 years. Researchers measured blood pressure to assess potential associations of individual metals with blood pressure and high blood pressure risk. Participants were categorized as having high blood pressure if blood pressure measures were greater than 130/80 mm Hg or if participants confirmed taking anti-hypertensive medication. In addition, the potential collective effects of all eleven metals and two micronutrients on blood pressure were analyzed.

The study found:

• After researchers adjusted for sociodemographic factors, as levels of copper and manganese doubled in the blood during pregnancy, the risk of high blood pressure in midlife was 25% and 20% lower, respectively.
• As blood levels of vitamin B12 doubled during pregnancy, women had an average 3.64 mm Hg lower systolic blood pressure and 2.52 mm Hg lower diastolic blood pressure almost two decades later. About 95% of the study participants had vitamin B12 levels within the normal range, the researchers noted.
• Blood levels of the mixture of copper, manganese, selenium and zinc were also associated with lower blood pressure in a relationship that increased with dose. Nonessential metals did not have a significant impact on blood pressure.

“Circulating levels of these metals and minerals in blood were measured, however, the sources of exposure, such as food or dietary supplements, were not quantified so these findings should not be interpreted as recommendations,” Zhang said. “Optimizing these essential metals, minerals and vitamins, particularly copper, manganese and vitamin B12, during pregnancy may offer protective benefits against hypertension in midlife, an especially critical time period for women’s future cardiovascular risk in later life.”

“More research including clinical trials is needed to determine the optimal dietary intake of these minerals and micronutrients,” he added. The researchers hope to ultimately identify women at high risk for developing high blood pressure later in life and intervene during pregnancy, either with enhanced nutrition or supplements.

Study details, background and design:

• The analysis included 493 women enrolled in Project Viva, a prospective study examining the effects of environmental and lifestyle factors during pregnancy on the short and long-term health of women and their children.
• Project Viva enrolled women in early pregnancy between 1999 and 2002. The women had a median age of 32.9 years at enrollment. Participants were followed for 18.1 years, through 2021.
• 72% of participants self-identified as white women; 11% were self-identified as Black women; and 17% self-identified as Hispanic or Latina, Asian or Pacific Islander, American Indian or Alaskan Native, or selected “Other” race, more than one race or “do not know.”
• Blood samples were collected at study enrollment and stored in freezers for subsequent analyses. The researchers accessed blood samples and analyzed them for this study in 2018. Folate and vitamin B12 were also measured in blood plasma samples during pregnancy.
• Blood pressure was measured in study participants during a “midlife” (median age of 51 years) study visit between 2017 and 2021. During this visit, trained research assistants measured participants’ blood pressure up to five times, at one-minute intervals. Blood pressure measurements were then averaged.
• The analyses were adjusted for maternal age at study enrollment, pre-pregnancy body mass index, race and ethnicity, education, household income, parity (the number of pregnancies carried to term), use of anti-hypertensive medication, DASH diet score in early pregnancy and multivitamin intake.

The study’s limitations include that it was an observational study, meaning other confounding factors that were not measured in the study may have affected the results; the researchers only included a subset of the original Project Viva participants; and there were demographic differences between participants included and excluded. In addition, the researchers did not have measurements for metal levels between delivery and midlife; and participants were predominantly white women who resided in Eastern Massachusetts, which may limit the generalizability of the study’s findings.