Kyoto Univ team eyes clinical test of platelets derived from iPS cells

A Kyoto University team plans to begin a clinical test using platelets grown from induced pluripotent stem cells to treat Aplastic anemia, a serious disease, sources with knowledge of the plan said Sunday.

The team led by professor Koji Eto is expected to begin the clinical test after getting approval from the Ministry of Health, Labor and Welfare. The university has already endorsed the plan.

Expectations are high in the field of regenerative medicine for iPS stem cells that can grow into any type of body tissue.

The world's first transplant of retinal cells grown from iPS cells into a patient has already been conducted and research is under way into the application of such cells to treat Parkinson's disease and heart failure.

So far, the team has established a method to produce high-quality platelets -- a key component of blood that can stem bleeding -- in large numbers through the use of iPS cells.

In the envisaged clinical test, the team plans to grow platelets from iPS cells from a patient. They will be injected into the patient to see the safety and effectiveness of the method, according to the sources.

Patients with Aplastic anemia are easy to bleed, get infections, and suffer from headaches as platelets and white blood cells decrease.

Patients with falling numbers of platelets are often treated with blood transfusions. But the patient in the upcoming clinical study has a special immune type and thus the use of platelets derived from the patient's own iPS cells can control rejection, the sources said.

Platelets are used in blood transfusions during surgery and to stem bleeding when people get injured.

Blood donations are one of the most useful ways to secure platelets for use in medical setting. But platelets can be used for a short period of time and ensuring stock is a challenge.


Source: Japan Today 

Japan Announces Physician-initiated clinical trials for Parkinson's disease using iPSCs

Kyoto University Hospital, in partnership with the Center for iPS Cell Research and Application (CiRA), Kyoto University, has planned physician-initiated clinical trials for Parkinson's disease that transplants dopaminergic progenitors1 generated from induced pluripotent stem (iPS) cells. The clinical trial notification was submitted to the Pharmaceutical and Medical Devices Agency (PMDA; the Japanese equivalent of the FDA) on June 4, 2018, and the clinical trials are scheduled to begin on August 1 this year.


Note: The candidate subjects are required to live in Japan, have Japanese public health insurance and can understand the Japanese informed consent form.


Outline of the Clinical Trials


1. Names


Selected patients will participate in both of the following clinical trials.


a) Kyoto Trial to Evaluate the Safety and Efficacy of iPSC-derived dopaminergic progenitors in the treatment of Parkinson's Disease (Phase I/II)


b) Kyoto Trial to Evaluate the Safety and Efficacy of Tacrolimus2 in the iPSC-based Therapy for Parkinson's Disease (Phase III)


2. Objectives


a) To evaluate the safety and efficacy of transplanting human iPS cell-derived dopaminergic progenitors into the putamen3 of Parkinson's disease patients.


b) To evaluate the safety and efficacy of using tacrolimus for Parkinson's disease patients who received transplantation of human iPS cell-derived dopaminergic progenitors into their putamen.


3. Strategy


Dopaminergic progenitors are generated from iPS cells prepared at the iPS Cell Stock for Regenerative Medicine4 at CiRA and then transplanted into the bilateral putamen of seven subjects (Parkinson's disease patients) at the Kyoto University Hospital. 


The source iPS cells were generated from third-party donor blood cells, meaning the transplantations will be allogeneic. Because of a possible transplant rejection, patients will receive a standard immunosuppressant, tacrolimus. Each subject will be observed for two years post transplantation.


4. The cell transplantation surgeryApproximately 5 million iPS cell-derived dopaminergic progenitors will be transplanted by stereotaxic brain surgery5 into the left and right sides of the patient's putamen. 


Glossary


1)Dopaminergic progenitorsDopaminergic neurons produce the neurotransmitter dopamine. In Parkinson's disease, these cells degenerate, resulting in decreased dopamine production. Dopaminergic progenitors differentiate into dopaminergic neurons. Animal studies have shown that transplanted progenitor cells will differentiate into mature dopaminergic neurons, resulting in efficient engraftment in the brain.


2)TacrolimusAn immunosuppressant commonly used following organ transplantation.


3)PutamenA region in the basal ganglia that is innervated by midbrain dopaminergic neurons.


4)iPS Cell Stock for Regenerative MedicineClinical-grade iPS cells are generated from healthy donors with specific cell types (HLA homozygosity) that are less likely to cause immune rejection in many people, and are stockpiled at CiRA following thorough quality check.


5)Stereotaxic brain surgeryThis neurosurgery involves drilling small holes on the patient's skull, through which a needle is entered or electrodes are embedded. One of the current therapies for Parkinson's disease, deep brain stimulation (DBS) surgery, is a type of the stereotaxic brain surgery.

Sources: CiRA PR 

Japan approves clinical trials of stem cell treatment for Parkinson's disease - Kyoto University to conduct first-ever iPS-based test for incurable disease

KYOTO (Kyodo) --  A Kyoto University research team said Monday it will begin this week a clinical test using induced pluripotent stem cells to treat Parkinson's disease, in what will be the world's first application of iPS to the progressive neurological disorder.

The team led by Jun Takahashi, a professor at the university's Center for iPS Cell Research and Application, has received government approval and is soliciting several patients to participate in the trial to be conducted at Kyoto University Hospital, according to sources close to the matter.

The team is scheduled to hold a press conference to explain the details of the clinical test later in the day.

Parkinson's disease reduces dopamine-producing neurons in the brain and results in tremors in the hands and feet, and stiffness in the body. While there are treatments to relieve the symptoms, there is currently no cure for the disease.

In the clinical test that will start on Wednesday, nerve cells derived from other people and stored at the university will be transplanted into the brains of patients to supplement damaged nerve cells.The team has already tested the process on monkeys in a preclinical study, in which the movement of the affected animals improved without seeing any tumors that could develop into cancer in the brain over a two-year observation period.

The clinical trial will be led by doctors who will determine the safety and effectiveness of the test.Among other clinical tests of iPS cells, the government-backed Riken institute conducted the world's first transplant of retinal cells grown from iPS cells to a patient suffering from a serious disease in 2014.

Osaka University is also planning a clinical test for treating heart failure by using a heart muscle cell sheet created from iPS cells.

Early Safety and Efficacy Data in Cynata’s Phase 1 Trial of CYP-001 in GvHD

Encouraging Early Safety and Efficacy Data in Cynata’s Phase 1 Trial of CYP-001 in GvHD; DSMB Recommendation to Initiate Enrolment of Second Patient Cohort

Australian stem cell and regenerative medicine company, Cynata Therapeutics Limited (ASX: CYP) announced that the independent Data Safety Monitoring Board (DSMB) has recommended that Cynata’s clinical trial of its lead Cymerus™ mesenchymal stem cell (MSC) product CYP-001 should progress to the next stage as planned.

Key Highlights:

• All eight participants in Cohort A (lower dose cohort) have demonstrated at least a Partial
Response (defined as an improvement in the severity of GvHD by at least one grade compared
to baseline)
• No treatment-related serious adverse events or safety concerns have been identified
• DSMB recommendation to progress clinical trial to second cohort (Cohort B)
• Patient enrolment in Cohort B (higher dose cohort) now open at seven trial sites in the U.K.
and Australia

Cynata’s clinical trial, which is the first clinical trial in which patients have been treated with an allogeneic, induced pluripotent stem cell (iPSC)-derived therapeutic MSC product, consists of a planned total of 16 patients with steroid-resistant acute graft-versus-host disease (GvHD). The recommendation to progress to the next stage (Cohort B) followed an independent review by the DSMB of the eight participants in Cohort A. Recruitment for Cohort A commenced in May 2017, and there are currently seven trial sites active and ready to enrol participants into Cohort B.

Steroid-resistant GvHD patients today have a dismal prognosis, where mortality rates are very high. At this time, seven of the eight participants in Cohort A are alive. One participant died after developing pneumonia, which is a common finding in recipients of bone marrow transplants and similar procedures.1 This death was not considered to be treatment-related. Participants enrolled in Cohort A of the dose-escalation trial received a dose of CYP-001 that was anticipated to be at the lower end of the effective dose range (one million cells per kilogram of bodyweight, up to a maximum of 100 million cells per infusion). In Cohort B, a further eight participants will receive two infusions of CYP-001 at a dose of two million cells per kilogram of bodyweight, up to a maximum of 200 million cells per infusion.

Dr Ross Macdonald, CEO of Cynata Therapeutics, said, “We are thrilled to report this encouraging early review of the Phase 1 trial of CYP-001, which marks the first time that patients have been treated with an allogeneic, induced pluripotent stem cell-derived therapeutic MSC product. The improvement in GvHD grade observed in 100% of these gravely ill people is very promising, especially given the low dose administered in Cohort A. The positive DSMB recommendation is an important milestone that enables us to begin enrolment in Cohort B, and advance toward our goal of completing the trial later this year. A successful outcome will support the application of CYP-001 in many medically and commercially significant targets where therapeutic MSCs have shown promising results.”

Next Steps:

Patient enrolment into Cohort B is now open at seven active sites across the U.K. and Australia. Cynata looks forward to providing further updates to the market as the study progresses.

Ref: Cynata PR