Replacement brain cells offer hope for Parkinson’s treatment

A colony of iPSCs from a Parkinson’s patient (left) and dopaminergic neurons made from these iPSCs (right) to model PD. (Image credit: Jeanne Loring)

A new study that used adult blood stem cells to create replacement brain nerve cells appears to help rats with Parkinson’s.

In Parkinson’s, the disease attacks brain nerve cells that produce a chemical called dopamine. The lack of dopamine produces a variety of symptoms including physical tremors, depression, anxiety, insomnia and memory problems. There is no cure and while there are some effective treatments they tend to wear off over time.

In this study, researchers at Arizona State University took blood cells from humans and, using the iPSC method, changed those into dopamine-producing neurons. They then cultured those cells in the lab before implanting them in the brains of rats which had Parkinson’s-like symptoms.

They found that rats given cells that had been cultured in the lab for 17 days survived in greater numbers and seemed to be better at growing new connections in their brains, compared to rats given cells that had been cultured for 24 or 37 days.

In addition, those rats given larger doses of the cells experienced a complete reversal of their symptoms, compared to rats given smaller doses.

In a news release, study co-author Dr. Jeffrey Kordower, said: “We cannot be more excited by the opportunity to help individuals who suffer from [a] genetic form of Parkinson’s disease, but the lessons learned from this trial will also directly impact patients who suffer from sporadic, or non-genetic forms of this disease.”

The study, published in the journal npj Regenerative Medicine, says this approach might also help people suffering from other neurological diseases like Alzheimer’s or Huntington’s disease.

Google eases ban on ads for stem cell therapies

What started out as an effort by Google to crack down on predatory stem cell clinics advertising bogus therapies seems to be getting diluted. Now the concern is whether that will make it easier for these clinics to lure unsuspecting patients to pay good money for bad treatments?

A little background might help here. For years Google placed no restrictions on ads by clinics that claimed their stem cell “therapies” could cure or treat all manner of ailments. Then in September of 2019 Google changed its policy and announced it was going to restrict advertisements for stem cell clinics offering unproven, cellular and gene therapies.

This new policy was welcomed by people like Dr. Paul Knoepfler, a stem cell scientist at UC Davis and longtime critic of these clinics. In his blog, The Niche, he said it was great news:

“Google Ads for stem cell clinics have definitely driven hundreds if not thousands of customers to unproven stem cell clinics. It’s very likely that many of the patients who have ended up in the hospital due to bad outcomes from clinic injections first went to those firms because of Google ads. These ads and certain particularly risky clinics also are a real threat to the legitimate stem cell and gene therapy fields.”

Now the search-engine giant seems to be adjusting that policy. Google says that starting July 11 it will permit ads for stem cell therapies approved by the US Food and Drug Administration (FDA). That’s fine. Anything that has gone through the FDA’s rigorous approval process deserves to be allowed to advertise.

The real concern lies with another adjustment to the policy where Google says it will allow companies to post ads as long as they are “exclusively educational or informational in nature, regardless of regulatory approval status.” The problem is, Google doesn’t define what constitutes “educational or informational”. That leaves the door open for these clinics to say pretty much anything they want and claim it meets the new guidelines.

To highlight that point Gizmodo did a quick search on Google using the phrase “stem cells for neuropathy” and quickly came up with a series of ads that are offering “therapies” clearly not approved by the FDA. One ad claimed it was “FDA registered”, a meaningless phrase but one clearly designed to add an air of authenticity to whatever remedy they were peddling.

The intent behind Google’s change of policy is clearly good, to allow companies offering FDA-approved therapies to advertise. However, the outcome may not be quite so worthy, and might once again put patients at risk of being tricked into trying “therapies” that will almost certainly not do them any good, and might even put them in harm’s way.

It’s hard to be modest when people keep telling you how good you are

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I have a confession. Deep down I’m shallow. So when something I am part of is acknowledged as one of the best, I delight in it (my fellow bloggers Katie and Esteban also delight in it, I am just more shameless about letting everyone know.)

And that is just what happened with this blog, The Stem Cellar. We have been named as one of the “22 best biology and stem cell blogs of 2022”. And not just by anyone. We were honored by Dr. Paul Knoepfler, a stem cell scientist, avid blogger and all-round renaissance man (full disclosure, Paul is a recipient of CIRM funding but that has nothing to do with this award. Obviously.)

We are particularly honored to be on the list because Paul includes some heavy hitters including The Signals Blog, a site that he describes this way:

“This one from our friends in Canada is fantastic. They literally have dozens of authors, which is probably the most of any stem cell-related website, and their articles include many interesting angles. They post really often too. I might rank Signal and The Stem Cellar as tied for best stem cell blog in 2021.”

Now I’m really blushing.

Other highly regarded blogs are EuroStemCell, the Mayo Clinic Regenerative Medicine Blog and Stem Cell Battles (by Don Reed, a good friend of CIRM’s)

Another one of the 22 is David Jensen’s California Stem Cell report which is dedicated to covering the work of, you guessed it, CIRM. So, not only are we great bloggers, we are apparently great to blog about. 

As a further demonstration of my modesty I wanted to point out that Paul regularly produces ‘best of’ lists, including his recent “50 influencers on stem cells on Twitter to follow” which we were also on.

Stem cell agency invests in therapy using killer cells to target colorectal, breast and ovarian cancers

While there have been some encouraging advances in treating cancer in recent decades, there are still many cancers that either resist treatment or recur after treatment. Today the governing Board of the California Institute for Regenerative Medicine (CIRM) approved investing in a therapy targeting some of these hard-to-treat tumors.

BioEclipse Therapeutics Inc. was awarded nearly $8M to test a therapy using immune cells loaded with a cancer-killing virus that targets cancer tissue but spares healthy tissue.

This is the 78th clinical trial funded directly by the Stem Cell Agency.

BioEclipse combines two approaches—an immune cell called a cytokine-induced killer (CIK) cell and a virus engineered to kill cancer cells called an oncolytic virus (OV)—to create what they call “a multi-mechanistic, targeted treatment.”

They will use the patient’s own immune cells and, in the lab, combine them with the OV. The cell/virus combination will then be administered back to the patient. The job of the CIK cells is to carry the virus to the tumors. The virus is designed to specifically attack and kill tumors and stimulate the patient’s immune system to attack the tumor cells. The goal is to eradicate the primary tumor and prevent relapse and recurrence.

“With the intent to develop this treatment for chemotherapy-resistant or refractory solid tumors—including colorectal cancer, triple negative breast cancer, ovarian cancer, gastric cancer, hepatocellular carcinoma, and osteosarcoma—it addresses a significant unmet medical need in fatal conditions for which there are limited treatment options,” says Dr. Maria T. Millan, President and CEO of CIRM.  

The CIRM Board also approved more than $18 million in funding four projects under the Translation Projects program. The goal of this program is to support promising regenerative medicine (stem cell-based or gene therapy) projects that accelerate completion of translational stage activities necessary for advancement to clinical study or broad end use.

The awards went to:

ApplicationTitleInstitutionAward Amount
TRAN1-133442Optogenetic therapy for treating retinitis pigmentosa and
other inherited retinal diseases  
  Paul Bresge Ray Therapeutics Inc.  $3,999,553  
TRAN3-13332Living Synthetic Vascular Grafts with Renewable Endothelium    Aijun Wang UC Davis  $3,112,567    
TRAN1-13370Next generation affinity-tuned CAR for prostate cancer    Preet Chaudhary University of Southern California  $5,805,144  
TRAN1-3345Autologous MPO Knock-Out Hematopoietic Stem and
Progenitor Cells for Pulmonary Arterial Hypertension  
  Don Kohn UC Los Angeles  $5,207,434  

Chance discovery could lead to a treatment for skin ulcers

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Dr. Antoni Ribas in his research lab on the UCLA Campus: Photo courtesy Ann Johansson

When UCLA’s Dr. Antoni Ribas was researching a potential therapy for melanoma, a form of skin cancer, he stumbled upon something unexpected. That unexpected discovery has now resulted in him getting a $5 million dollar award from the the governing Board of the California Institute for Regenerative Medicine (CIRM) to develop a therapy to accelerate wound healing in legs.

Venous skin ulcers are open sores on the legs that can take weeks, sometimes even years, to heal and that can cause serious complications if not treated. Around 1% of Americans have venous skin ulcers. They are usually caused by insufficient blood flow from the veins of the legs back to the heart.  The resulting increased blood pressure and swelling in the legs can cause an open wound to form that is painful and difficult to heal, seriously impacting quality of life.   Those most at risk of developing venous leg ulcers are older people, women and non-white populations.

There are no drugs approved by the US Food and Drug Administration (FDA) for this condition and sometimes these ulcers can lead to serious skin and bone infections and, in rare cases, even skin cancer.

In a news release from UCLA, Dr. Ribas describes how his team were testing a drug called vemurafenib on patients with melanoma. Vemurafenib falls into a category of targeted cancer drugs called BRAF inhibitors, which can shrink or slow the growth of metastatic melanoma in people whose tumors have a mutation to the BRAF gene. 

“We noticed that in the first two months of taking this BRAF inhibitor, patients would begin showing a thickening or overgrowth of the skin. It was somewhat of a paradox – the drug stopped the growth of skin cancer cells with the BRAF mutation, but it stimulated the growth of healthy skin cells.”

That’s when the team realized that the drug’s skin stimulating effect could be put to good use for a whole other group of patients – those with chronic wounds. 

“Aside from a few famous cases, discovering a side effect that becomes a therapeutic isn’t that common,” Ribas said. “For this reason, I had to work hard to convince somebody in my lab to follow my crazy idea and take time away from immunotherapy research and do wound healing experiments.”

Thanks to that “crazy idea” Dr. Ribas and his team are now testing a gel called LUT017 that stimulates skin stem cells to proliferate and produce more keratinocytes, a kind of cell essential for repairing skin and accelerating wound healing.

The CLIN1 grant of $5,005,126 will help them manufacture and test LUT017 in pre-clinical models and apply to the FDA for permission to study it in a clinical trial in people.

Maria T. Millan, CIRM’s President and CEO says “This program adds to CIRM’s diverse portfolio of regenerative medicine approaches to tackle chronic, debilitating that lead to downstream complications, hospitalization, and a poor quality of life.”

Promoting stem cell therapies, racial justice and fish breeding

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Jan Nolta, PhD, in her lab at UC Davis; Photo courtesy UC Davis

Working at CIRM you get to meet many remarkable people and Dr. Jan Nolta certainly falls into that category. Jan is the Director of the Stem Cell Program at UC Davis School of Medicine. She also directs the Institute for Regenerative Cures and is scientific director of both the Good Manufacturing Practice clean room facility at UC Davis and the California Umbilical Cord Blood Collection Program.

As if that wasn’t enough Jan is part of the team helping guide UC Davis’ efforts to expand its commitment to diversity, equity and inclusion using a variety of methods including telemedicine, to reach out into rural and remote communities.

She is on the Board of several enterprises, is the editor of the journal Stem Cells and, in her copious spare time, has dozens of aquariums and is helping save endangered species.

So, it’s no wonder we wanted to chat to her about her work and find out what makes her tick. Oh, and what rock bands she really likes. You might be surprised!

That’s why Jan is the guest on the latest edition of our podcast ‘Talking ‘Bout (re)Generation’.

I hope you enjoy it.

HOPE for patients with a muscle destroying disease

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Caleb Sizemore, photo by Todd Dubnicoff

Caleb Sizemore says growing up with Duchenne’s Muscular Dystrophy (DMD) was tough. The disease is a rare genetic disorder that slowly destroys a person’s muscles, impairing their ability to walk or breathe. Eventually it attacks the heart leading to premature death.

Caleb says the disease meant “I was limited in what I could do, where I couldn’t play sports and where I was teased and bullied sometimes for being different.”

In the past people with DMD – almost all of whom are boys – lost the ability to walk by the age of 12, and many died in their 20’s. But a new treatment – originally funded by CIRM – is showing promise in helping reverse some of the damage caused by the disease.

Dr. Craig McDonald working with a person who has DMD: Photo courtesy UC Davis

Results from a clinical trial – published in the journal Lancet – showed that the therapy helped halt the decline in muscle strength in the arms and hands, and in MRI’s appeared to improve heart function.

In a news release, Dr. Craig McDonald, a UC Davis professor and the lead author of the study, said: “The trial produced statistically significant and unprecedented stabilization of both skeletal muscle deterioration affecting the arms and heart deterioration of structure and function in non-ambulatory DMD patients.”

The therapy, called CAP-1002, uses cells derived from the human heart that have previously demonstrated the ability to reduce muscle inflammation and enhance cell regeneration. The clinical trial, called HOPE-2 (Halt cardiomyopathy progression in Duchenne).

Dr. McDonald says with current treatments only having a limited impact on the disease, CAP-1002 may have a big impact on the people affected by DMD and their families.

“The trial showed consistent benefits of this cell-based therapy. It suggests that this infusion may be an important treatment option for the boys and young men who have this debilitating disorder.”

The team now hope to be able to apply to the Food and Drug Administration for permission to start a bigger clinical trial involving more patients.

Caleb Sizemore took part in an earlier clinical trial involving this approach. He says MRI’s showed that the therapy appeared to reduce scarring on his heart and gave him greater energy.

In 2017 Caleb talked to the CIRM governing Board about DMD and his part in the clinical trial. You can see that video here.

Stem Cell Agency Hires New Vice President of Medical Affairs & Policy

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Dr. Sean Turbeville

Sean Turbeville PhD. is joining the California Institute for Regenerative Medicine (CIRM) as the Vice President of Medical Affairs and Policy.

Dr. Turbeville has almost 20 years of experience in Medical Affairs, creating strategies and teams for biopharma and digital healthcare companies. He has experience supporting the development of therapies in cancer, neurology, metabolic and genetic disorders and in working with Regulatory Authorities such as the Food and Drug Administration, EMA and others.  

Sean has a PhD in Epidemiology from the University of Oklahoma Health Sciences Center where he later taught courses as an Adjunct Associate Professor. He is the owner of two global regulatory resources for biopharma, “The Global Regulatory Framework for Medical Information in the Pharmaceutical Industry” and “The Global Guide to Compassionate Use Programs”. Before joining CIRM, Dr. Turbeville was the President of Matanzas Group, a Medical Affairs consultancy providing a range of Medical Affairs services to over 20 small, growing biopharmaceutical companies.  

CIRM’s Vice Chair, Sen. (ret) Art Torres says Dr. Turbeville is a great addition to the team: “Sean’s expertise will be invaluable to our working group and to our coordination with the Governor and Legislature on affordability and accessibility issues affecting patients.”

“I am honored to work at CIRM, where science, business, regulatory and policy work together to accelerate world class science and provide Californians equal accessibility to novel therapies,” says Dr. Turbeville. “It’s a unique opportunity to give back to the state that has given me and my family so much.”   

The VP of Medical Affairs and Policy is a new position and Dr. Turbeville will have responsibility for overseeing a Medical Affairs Team that will work with the CIRM team, the Accessibility and Affordability Working Group and the board to develop healthcare policy, reimbursement strategy, post-market activities and research. He will also oversee and develop CIRM’s infrastructure programs for clinical trials and the delivery of therapies, in particular the Alpha Clinics Network and the future Community Care Centers of Excellence.

“As CIRM drives more transformative regenerative therapies to the clinics, we set a bold strategic goal to deliver a roadmap for access and affordability of these treatments to all patient communities. We are extremely excited to have Sean as a qualified leader and expert in the field to lead this charge,” says Maria Millan, CIRM’s President and CEO. “He has been a mission-driven patient advocate and board member of the Cholangiocarcinoma Foundation which he joined after losing his father. In this role, he drove the creation of alliances with companies to increase access to clinical trials for patients with this devastating cancer.”

Dr. Turbeville joins the growing ranks of new team members that CIRM has hired since the passage of Proposition 14 in November 2020. CIRM is rebuilding and expanding its team to meet new challenges and advance the mission of the agency.

Among the new hires is Linda Nevin, PhD, who joined us as a Senior Science Officer on the Review and Portfolio Development Team. Linda is a former Associate Editor for the journal PLOS Medicine and brings detailed experience with data sharing, health equity research, large cohort studies, and machine learning in medicine.Linda got her PhD in Neuroscience from UCSF and has a BS/MS in Biological Sciences from Stanford.

Katie Sharify is the new Communications Team Coordinator, but she has a long history of involvement with CIRM. More than ten years ago Katie was a patient in the first clinical trial CIRM funded, a stem cell therapy aimed at helping people with spinal cord injuries. Since then, Katie has been a tireless supporter and advocate on behalf of CIRM, so we were delighted to be able to make her a full-time member of the team.

Maziar Shah Mohammed, PhD, a Senior Science Officer in our Scientific Programs group, has undergraduate and master’s degrees in Materials Science and Engineering and he got his PhD in Biomaterials and Tissue Engineering from McGill University in Canada. He comes to CIRM with experience in academic research, the medical device industry and, most recently as a Lead Reviewer at the U.S. Food and Drug Administration (FDA) in the Center for Devices and Radiological Health (CDRH).

Lisa McGinley, PhD, joined CIRM as a Senior Science Officer in Therapeutics and Development. She has expertise in stem cell therapy discovery, development and translation in cardiovascular and neurology spaces. She received her PhD in Regenerative Medicine from the National University of Ireland, Galway and completed her postdoctoral fellowship in Bioengineering at the Georgia Institute of Technology. Most recently she was an Assistant Professor in Neurology at the University of Michigan, where she led an NIH-funded collaborative stem cell initiative developing therapeutics for ALS and Alzheimer’s disease. 

Treecy Truc Nguyen is CIRM’s new Project Manager in the Therapeutics Development group. Treecy got her BSHS and MPH from Massachusetts College of Pharmacy and Health Sciences. Before joining CIRM she was the Senior Systems Manager at The Unity Council, a non-profit community development organization committed to social equality and improving the quality of life in traditionally underserved communities.

The new team members are:

  • Claudette Mandac
    Project Manager, Review 
  • Mitra Hooshmand
    SSO, Special Projects and Strategic Initiatives
  • Vanessa Singh
    HR Manager
  • Pouneh Simpson
    Director of Finance
  • Alexandra Caraballo
    Grants Management Specialist
  • Kevin Marks
    General Counsel
  • Michael Bunch
    Business Services Officer
  • Rosa Canet-Aviles
    Vice President, Science
  • Uta Grieshammer
    SSO, Science
  • Linda Nevin
    SSO, Review and Portfolio
  • Stephanie Bautista
    Executive Assistant to the President
  • Mason Saia
  • Software Engineer
  • Marianne Villablanca
    Associate Director, Board Relations
  • Katie Sharify
    Communications Team Coordinator
  • Lisa McGinley
    SSO, Therapeutics
  • Esteban Cortez
    Director, Marketing and Communications
  • Maziar Shah Mohammadi
    SSO, Scientific Programs
  • Treecy Truc Nguyen
    Project Manager, Therapeutics
  • Sean Turbeville
    Vice President, Medical Affairs & Policy

Joining the movement to fight rare diseases

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It’s hard to think of something as being rare when it affects up to 30 million Americans and 300 million people worldwide. But the truth is there are more than 6,000 conditions – those affecting 200,000 people or fewer – that are considered rare.  

Today, February 28th, is Rare Disease Day. It’s a day to remind ourselves of the millions of people, and their families, struggling with these diseases. These conditions are also called or orphan diseases because, in many cases, drug companies were not interested in adopting them to develop treatments.

At the California Institute for Regenerative Medicine (CIRM), we have no such reservations. In fact last Friday our governing Board voted to invest almost $12 million to support a clinical trial for IPEX syndrome. IPEX syndrome is a condition where the body can’t control or restrain an immune response, so the person’s immune cells attack their own healthy tissue. This leads to the development of Type 1 diabetes, severe eczema, damage to the small intestines and kidneys and failure to thrive. It’s diagnosed in infancy, most of those affected are boys, and it is often fatal.

Taylor Lookofsky (who has IPEX syndrome) and his father Brian

IPEX is one of two dozen rare diseases that CIRM is funding a clinical trial for. In fact, more than one third of all the projects we fund target a rare disease or condition. Those include:

Some might question the wisdom of investing hundreds of millions of dollars in conditions that affect a relatively small number of patients. But if you see the faces of these patients and get to know their families, as we do, you know that often agencies like CIRM are their only hope.

Dr. Maria Millan, CIRM’s President and CEO, says the benefits of one successful approach can often extend far beyond one rare disease.

“Children with IPEX syndrome clearly represent a group of patients with an unmet medical need, and this therapy could make a huge difference in their lives. Success of this treatment in this rare disease presents far-reaching potential to develop treatments for a larger number of patients with a broad array of immune disorders.”

CIRM is proud to fund and spread awareness of rare diseases and invites you to watch this video about how they affect families around the world.

It’s nice to be appreciated

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Photo: courtesy City of Hope

No one likes to be taken for granted, to feel that people only like you because you have scads of cash and they want some of it. That’s why it’s so lovely when you feel you are appreciated because of all the things money makes possible.

That’s how it felt when we saw City of Hope’s news release about our funding to train the next generation of scientists and leaders in the field of regenerative medicine. CIRM has awarded COH $4.86 million as part of its Research Training Program in Stem Cell Biology and Regenerative Medicine.

The program provides stem cell and gene therapy research training for up to 6 graduate students and 12 postdocs at the Beckman Research Institute of City of Hope. In addition to 3 years of research, the training includes coursework, patient engagement and community outreach activities.

In a news release, Dr. Nadia Carlesso, chair of the Department of Stem Cell Biology and Regenerative Medicine, said this funding is important in training a new generation of scientists.

“This program originates from City of Hope’s longstanding expertise in conducting clinical trials and applying fundamental stem cell biology and gene therapy to the treatment of diseases. The program reflects City of Hope’s commitment to ensuring that future scientific leaders understand the varied needs of diverse patient populations, and the inequities that presently affect both biomedical research and the development of and access to innovative therapies.”

Students in the program will have access to world class research facilities and will also benefit from the fact that their classrooms and laboratories are within walking distance from where patients are treated. We believe the best scientists need to have experience in working both at the laboratory bench and at the bedside, not only developing new therapies, but being able to deliver those therapies in a caring, compassionate way.