Friday, June 27, 2014

New California stem cell chief stresses speed and efficiency in search for treatments

A major hope of those facing Huntington's disease (and numerous other diseases) resides in stem cell research.

The new president and CEO of the California Institute for Regenerative Medicine (CIRM), transferring from the pharmaceutical industry, has assumed the helm of the $3 billion organization stressing efficiency, including a pledge to prioritize speedier development of treatments for the many diseases falling within the agency’s scope.

“What I promise I will do is to bring stem cell therapies and treatments to the patients that need them,” C. Randal Mills, Ph.D., chosen to run CIRM by its board of directors on April 30, said in San Diego on June 24 at the third of three “Meet the New CIRM President” events. “That is quite sincerely what I have done my entire career, and the only thing I care about and the only reason I came to CIRM.”

Dr. Mills was introduced by CIRM board chair Jonathan Thomas, J.D., Ph.D. The meeting took place in conjunction with the 2014 BIO International Convention, June 23-26, which showcased the work of leading biotech firms and featured a keynote speech by British business magnate Sir Richard Branson and a moderated Q & A with former Secretary of State and potential 2016 presidential candidate Hillary Rodham Clinton. The convention attracted more than 15,000 participants from all 50 states and 70 countries.

Dr. Mills outlined four questions he said will guide him in decision-making at CIRM.

First, he said, "is whatever we're doing speeding up a treatment reaching a patient?"

Secondly, will CIRM’s activities increase the likelihood of a treatment reaching a patient? There are many “valleys of death,” or dead ends, in stem cell research, Dr. Mills noted.

Third, is CIRM meeting an unmet medical need, as opposed to a condition already successfully dealt with by other medical means?

Fourth, is CIRM doing all this efficiently?

Randy Mills speaks to disease advocates and stem cell industry representatives in San Diego (photo by Gene Veritas).

Taking care of patients

Dr. Mills said his patient-oriented outlook started during his undergraduate studies in microbiology and cell studies at the University of Florida, in Gainesville.

“During that time I worked as a medic in the emergency room,” he told the audience. “I saw and dealt with a lot of patients and got a pretty good sense of what patient care was like and delivery was like.”

Dr. Mills obtained his Ph.D. in drug development, also at the University of Florida. After that, he worked for the university as a specialist in orthopedic transplants. With a partner, Jamie Grooms, he started a company within the university specializing in spinal fusion, one of the most common of orthopedic procedures.

In 1995, the two “spun out” the company from the university, calling it University of Florida Tissue Bank. That year the company had $1 million in revenues, with only six employees. Five years later, when the firm went public, it had 550 employees and annual revenues of $120 million.

“More importantly, (we were) producing regenerative medicine solutions for patients all across the United States on the scale of hundreds of thousands of implants, and better implants, a year,” Dr. Mills explained.

“It was during that time that I really learned a lesson. And the key lesson is: if you take care of patients, then your business is going to follow. If you don’t take care of the patients, there is nothing you can do in order to get your business to come along.”

Randy Mills (Osiris photo)

Key achievements at Osiris

In 2004, at the age of 32, Dr. Mills was recruited to become the president and CEO of Osiris Therapeutics, Inc., a Columbia, Md.-based company that commercialized the world’s first stem cell product, Osteocel, for bone regeneration. According to Mills, that product has brought a total of $1.5 billion in revenue to Osiris.

Under his leadership, in May 2012 Osiris received approval to market the world’s first systemically infused stem cell drug, Prochymal, which it developed to combat pediatric acute graft-versus-host disease. (It was approved in Canada but is also available in the U.S.; click here to read more.)

This condition occurs in patients receiving bone marrow transplants that reject the person and attack the body.

“Patients will literally peel out of their skin,” Dr. Mills said, describing the horrors of the condition. Patients with the condition have a life expectancy of only 87 days, he added.

With Prochymal, patients got better two-thirds of the time, he said.

Dr. Mills attributed Osiris’s success to its intense focus on patients.

“The board room is covered with pictures of our patients,” he said.

“That’s my mission with CIRM,” he continued. “We’re going to focus on the patients, and everything else is going to come along. If you get a sense of urgency from me, it’s because, if a life expectancy of a disease is 87 days, missing a month or two months or three months are actually real patients dying.”

Putting criticisms of CIRM in perspective

The stem cell board’s selection of a new CEO with long experience in the drug industry takes place a decade after California voters created CIRM by approving Proposition 71, the California Stem Cell Research and Cures Act.

According to CIRM’s statistics, so far four clinical trials directly funded by the organization have taken place – including an observational study of Huntington’s disease patients at the University of California, Davis, the basis for a potential CIRM-supported treatment trial envisioned by Dr. Vicki Wheelock and Dr. Jan Nolta (click here to read more).

Six additional trials for different conditions are based on “discoveries made by our grantees when they were carrying out CIRM-funded research,” CIRM reports (click here to read more).

According to Kevin McCormack, CIRM’s senior director for public communications and patient advocate outreach, five more directly funded trials for various diseases will start by the end of 2014.

CIRM’s efforts have not yet produced a drug, although one or more treatments could arise from the clinical trials.

Some in California have criticized CIRM’s performance. The San Francisco Chronicle, for instance, editorialized that CIRM “hasn’t lived up to its hype” and has compiled a “decidedly mixed” record, although it recognized that California voters had “outsize expectations when they passed Prop. 71.”

The Chronicle further noted that “it’s been a struggle to get the agency to use the best organizational practices. In 2012, a blue-ribbon committee of the National Academy of Sciences released a report after a yearlong review that found conflicts of interest on the CIRM board that threatened to ‘undermine respect for its decisions.’ It also found significant flaws in the agency’s grant-approval process.”

The editorial added: “Progress on stem cell research has been significant – but it’s been the progress of the tortoise rather than the hare.”

In general, news coverage of CIRM has been sporadic. After all, news outlets typically don’t report on the work of scientists in the trenches.

In this blog, I have provided frequent coverage of HD science as well as related stem cell research. In my 15 years writing about HD science, I’ve learned that scientific progress is slow by nature. It’s not just the CIRM projects that take a long time to produce results.

From my standpoint, stem cell science has produced a “growing array of possibilities” for treatments and the “potential for a new era in human health,” as I noted after attending the 2013 World Stem Cell Summit (click here to read more).

Producing treatments is also extremely expensive. According to Jim Greenwood, president and CEO of the Biotechnology Industry Association, which organized the Bio Convention, developing a new drug in the U.S. costs an average of $1.2 billion. CIRM and/or its affiliated researchers will need to partner with the pharmaceutical industry to bring treatments to market.

In the HD community, we earnestly hope for stem cell treatments, but we’re also aware that a “cocktail” of different approaches (like gene therapy) will likely be needed to deal with the complexities of the disease. We’re rooting for all the researchers to find keys to treatments.

Crucial experience with clinical trials

With the need to show results, it’s not surprising the CIRM board chose a new CEO from the business world.

As noted by David Jensen, author of the blog California Stem Cell Report, CIRM’s previous two presidents, Zach Hall, Ph.D., and Alan Trounson, Ph.D., came from “largely academic and non-business backgrounds…. Decisions are likely to come faster under Mills.”

In his introduction of Dr. Mills at the San Diego meeting, CIRM board chair Dr. Thomas said that the new CEO met the many qualifications sought by the organization, including familiarity with the process of running stem cell clinical trials and seeking approval of drugs from governmental agencies.

“Very few people can say they’ve had more experience in clinical trials in stem cells,” Dr. Thomas said. “Very few people can say they’ve had more experience with the regulators, not just from the U.S., but from other countries as well.”

Randy Mills (left) and CIRM board chair Jonathan Thomas (CIRM photo)

The board also sought someone familiar with CIRM. Dr. Mills has spent the last five years as a reviewer of proposals made to CIRM by stem cell researchers seeking funding. (Click here to read more.)

During the audience Q & A, one woman asked Dr. Mills what he would do to make the grant review process more “transparent.”

Recognizing that the process wasn’t “perfect,” Dr. Mills nevertheless said he believed it was “pretty good” and already “remarkably transparent,” with world experts involved in the reviews. He reminded the audience that no “divining rod” exists to pick perfect projects. He added that he will work for quicker approval of worthy applications.

Keeping CIRM running

Jeanne Loring, Ph.D., a leading expert on stem cells and Parkinson’s disease at The Scripps Research Institute in San Diego, wanted to know how Dr. Mills would prioritize CIRM spending from now through 2017, when the last of the agency’s grants will be made and the original CIRM allocation of $3 billion might run out.

The agency still has about $600 million in uncommitted funds. In all, $1.5 billion of its $3 billion budget has yet to be spent, as many budgeted projects remain in progress.

“Let’s be careful on speculating on when CIRM is going to run out of money,” Dr. Mills said in response to Dr. Loring’s question. “That (2017) would be the absolute earliest. This is an important thing for people to understand: in order for that date to be true, things have gone incredibly well. Everything we funded, 100 percent of it, has worked. If that ‘17 date happens, I’m a happy guy, because we are rattling off diseases left and right.”

Dr. Mills explained that CIRM does “milestone-based funding.”

So we’ll fund your project, but if you don’t hit your milestone, if it’s not working, we stop funding,” he continued. “That seems like a pretty good idea. So the projections on these running out of money is assuming that everything is going along. Everything’s going along, and we can’t get California to say, ‘Let’s keep doing it’? In a more practical sense, we’re not going to run out of money by then, and everything’s not going to work perfect. My job is to run CIRM as efficiently as we possibly can to develop treatments.”

According to spokesperson McCormack, the CIRM board can still redirect funding from the $1.5 billion as yet unspent. If a project comes in under budget, CIRM can also redirect savings to other projects, he added.

Some stem cell advocates such as Don Reed, who served on the executive board for the Prop 71 campaign, are already advocating a second round of CIRM funding to be requested from the state by way of another ballot proposition to be put before the voters. (You can watch Reed, HD advocate Judy Roberson, and children’s neurological disorders advocate Alex Richmond speak about their experiences by clicking here.)

Dr. Thomas has also spoken publicly about seeking private sources of funding for CIRM. In this vein, Dr. Mills’ experience in capital markets – one of the sought-for qualities in a CEO noted by Dr. Thomas – could prove helpful.

"California (undertook) a very important task in creating a funding stream for stem cell research," Clinton, referring to CIRM, said during her Q & A at the Bio Convention. "Other states have followed suit, when it looked as though the federal government would not be doing that. States have a role to play, but we need a national framework."

Our urgency for cures

Huntington’s disease advocates participated in the “Meet the New CIRM President” events in San Diego as well as Los Angeles and San Francisco.

One of those participants, veteran advocate Frances Saldaña of Orange County, sees Dr. Mills’ appointment as a positive step.

“I really liked Randy Mills,” Saldaña, a mother of three children stricken with juvenile HD, told me in an e-mail about her encounter with Dr. Mills at the June 10 Los Angeles meeting. “I feel that he really understands our urgency to find cures.”

Saldaña’s daughter Margie Hayes – who became one of the very first HD patients to advocate for CIRM support for Huntington’s stem cell research when she spoke at a December 2007 CIRM board meeting – succumbed to the disease on February 7. Hayes had just turned 44. She is survived by her husband Craig and two teenaged children.

Saldaña’s husband also died of HD, which has afflicted several other members of her extended family. She was recently presented the 2014 Living Our Values Award by Michael Drake, the chancellor of the University of California, Irvine (UCI), for her work in HD community service. Saldaña is the founder of HD-CARE, an Orange County care organization affiliated with UCI’s Institute for Memory Impairments and Neurological Disorders.

Saldaña said of Dr. Mills: “In the case of HD families, he completely understands that we're in a race against time, as our families are dying.”

As mother Frances Saldaña (left) looks on, Margie Hayes tells about her struggle against HD at the CIRM Spotlight on Huntington's Disease, Los Angeles, December 12, 2007 (photo by Gene Veritas).

Tuesday, June 17, 2014

Fear of onset: the inescapable reality of the Huntington’s disease gene carrier

As a carrier of the devastating and ultimately deadly genetic mutation for Huntington’s disease, I have worked hard to live as normally as possible. This blog is replete with examples of coping strategies and ways in which I have strived to balance work, leisure, family, and HD advocacy.

At 54, my HD-stricken mother was rapidly declining, heading towards a troubling and terrible death at the age of 68. Today, at 54, I continue to enjoy the gift of good health – the major reason I can often feel “normal.” Scientists are searching to discover the reasons for the wide variability in the age of onset observed in people, like my mother and me, who have the same level of mutation.

Yet my fear of onset often creeps back in.

Recalling a time of innocence

The past few weeks I’ve been so busy with the “normal” that I’ve had no time to write in this blog.

At work, I’m transitioning from five-and-a-half years as departmental chair to a year-long sabbatical, during which I aim to write a long-gestating book on the history of former Brazilian radicals now in positions of power. I’m also teaching an intensive, three-week summer session course on the history of Mexico. The next year promises to be an engaging, challenging time.

The transition has required an understandably disruptive move to a new office, but also allowed me to dispose of unneeded books and papers.

As I rummaged through old files and letters, I found myself reminiscing about the seemingly innocent period of my life before Huntington’s struck my mother.

It would be great, I thought, not to have to worry about onset. Without the threat of HD, which led me to expand my scholarly endeavors into the history of science, technology, and medicine, I could once again focus exclusively on the history of Brazil.

Watching for early symptoms

I’m also working out the logistics for my upcoming trip to the University of Iowa in Iowa City for my follow-up participation in PREDICT-HD.

An “observational study of the earliest signs of Huntington’s disease,” PREDICT-HD has aimed at creating key standards for predicting onset and measuring the rate of disease progression.

I’ll be staring onset in the face – and wondering about my performance on the battery of tests.

A visit to Auspex

I discussed my fear of onset and reiterated our community’s urgent need for effective treatments in an intense, 80-minute get-acquainted conversation last week with Pratik Shah, Ph.D., the president and CEO of Auspex Pharmaceuticals.

An investor-funded San Diego firm focused exclusively on central nervous system disorders and orphan diseases, Auspex struck me as made-to-order for the fight against HD. It is currently conducting clinical trials for a drug called SD-809, aimed at treating chorea, the involuntary abnormal movements produced by HD.

SD-809 (dutetrabenazine) is a potentially improved version of tetrabenazine, a chorea treatment currently marketed by the pharmaceutical company Lundbeck under the name Xenazine. If SD-809 works as intended, it will require fewer dosages and produce fewer side effects than tetrabenazine.

However, tetrabenazine does not affect the root causes of HD, nor is SD-809 expected to.

Auspex seeks to use SD-809 as a platform to research and develop drugs that would attack those causes.

Dr. Shah and I agreed to schedule soon an interview so that I can write an in-depth article on Auspex’s efforts.

I told Dr. Shah about a middle-aged, HD-afflicted man I had met who had maintained much of his cognitive abilities but suffered from strong chorea. However, tetrabenazine controlled the chorea, enabling him to keep driving, something most HD patients have to give up.

Tetrabenazine’s approval by the Food and Drug Administration had come too late to benefit my mother, who died of HD in 2006. I told Dr. Shah that she had taken another medication to control her chorea, which was relatively mild, although she had initially had strong chorea in her legs at night. In general, chorea was the least of my mother’s problems with HD, which devastated her cognitive abilities and caused serious psychiatric difficulties.

I also related my recent conversation with a former HD support group colleague who has had symptoms for a number of years.

Speaking to a symptomatic individual, I pointed out, provides me a terrifying glimpse of my own future.

A powerful HD dream

As I processed these latest events in my journey with HD, my unconscious mind produced a powerful dream.

I awoke from the dream at 5 o’clock on Sunday morning. Afraid that I would forget its content, I went to my home office to type out the details on my computer, and to outline this article.

In the dream, where I am meeting with other asymptomatic HD gene carriers, I encountered the same HD-affected man whom I had mentioned to Dr. Shah.

The people in our dreams often represent aspects of ourselves. In my interpretation, thinking of a symptomatic man in the context of a group for the asymptomatic meant that I was wrestling with the inevitable reality of my onset.

Tapping into the soul

As the dream continues, I fly to New York City on HD advocacy business.

In my hotel room, I start to write a blog article describing the recent HD-related aspects of my life. I have my trusty laptop with me but am oblivious to it. Instead, I write in longhand on a white legal pad. It’s the way I sometimes wrote in college or now write on airplanes or when I’m revising a draft I’ve printed out.

There’s something pure and primal about this form of writing. It’s the way I first learned to write. I’m crossing things out, jotting down ideas, and flipping back and forth through the pages to read and make adjustments. At one point I think that, because I don’t have much time before my evening HD meetings, I’ll switch to the computer. But I want to first eke out some more lines on the pad.

The dream was compelling me to practice the craft I have enjoyed since childhood, to tap into the soul that defines me.

I later recalled the photograph that an HD-affected man posted of himself illustrating his superb kickboxing skills before the disease struck. He wanted to remember himself at the height of his powers.

The dream, I think, reflected my fear that HD will rob me of my writing skills.

A metaphor for facing HD

Later in the dream, I go to a restaurant along with two other asymptomatic gene carriers and my friend, blog editor, and HD alter ego, Norman. One of the gene carriers, I recognize, is the symptomatic man I’d encountered earlier in the dream, only transformed into a healthy individual. On the way there, I give each gene-positive man a bear hug. I feel deep brotherly love towards these men.

A native New Yorker, Norman describes the restaurant as a very different and unique place. He says it’s called Pub Med.

We seem to be on the Upper West Side of Manhattan. Evening is approaching.

The restaurant is made of recently hewn, unpainted pieces of wood, which are also used as furniture: benches and small, round tables. It’s outdoors, located in the middle of a square where I can hear kids playing on swings and moms walking their kids. There are small stores on the edges of the square, too.

But there’s something very strange: the benches and tables are stacked on top of one another in a pyramid-like fashion. They rise about 30 feet. We climb up and look for a place to sit. Norman is sitting with the first gene-positive person while, at another table, the second gene carrier continues to explain to me the nature of this restaurant-structure and how to sit on it without falling.

I'm still standing. However, as I try to sit down, some of the tables and benches near me shift down or fall off suddenly and unpredictably. I’m afraid that I’ll fall off. The second gene carrier seems to know well how to deal with it. He’s experienced and seems to take it all in stride.

As I strive to keep my balance on the structure, I gaze at a different kind of Manhattan skyline. On the horizon, I see some burning buildings. Referring to the restaurant-structure and the buildings ablaze in the distance, I tell the second gene carrier: “I can think of no better metaphor to describe living at risk for Huntington’s disease.”

Building hope, pondering onset

The dream, I think, represented my fight to continue advocating for the HD cause.

Manhattan is headquarters for three key HD organizations: the CHDI Foundation, Inc., the Hereditary Disease Foundation, and the Huntington’s Disease Society of America. Along with other organizations and scientists around the world, they hold the key to finding treatments.

Norman has taken my family and me on a walking tour of Manhattan. He urged me to start this blog. In both the dream and real life, he has acted as a kind of guardian angel in my fight against HD. I believe that the Norman of the dream also symbolizes my own internal editor, who, like the real-life Norman, the author of a richly detailed and public-spirited watchdog blog on Brooklyn's Atlantic Yards project, strives to produce in-depth and understandable reports.

Along those lines, I had told Dr. Shah I would read scientific articles about SD-809 before our planned interview. I believe that the Pub Med restaurant represents my desire to prepare thoroughly for an interview regarding the potentially life-saving work done at Auspex. In reality, PubMed, a well-known research tool, has more than 23 million citations from biomedical literature, life science journals, and online books.

I explained to Dr. Shah that in this blog I seek to provide the HD community with information about potential treatments, breakthroughs, and challenges.

My goal is to provide the community with hope, and advocate for change.

The dream, I believe, also reflected my continued striving for internal equilibrium as I ponder the kind of onset I will experience.

Will I falter like an HD person who can no longer control movements and mind? Will I continue to work and drive? Will I be able to help support my daughter as she studies in college? Will effective treatments arrive in time to at least reduce the severity of symptoms – and prolong my life?

These are the inescapable questions of my reality as a Huntington’s disease gene carrier.