3 thoughts on “Two words

  1. For an unheard-of two years, stem cells have slowed the progression of Lou Gehrig’s disease, a devastating condition with a two-to-five year survival rate, in a small group of patients.

    “We have now extended the lives of patients with Amyotrophic Lateral Sclerosis (ALS) and significantly improved the quality of their lives. They are now living high-quality lives with this disease,” says Neuralstem CEO Richard Garr.

    For 700-800 days, human fetal neural stem cells, cultivated by Neuralstem, have substantially slowed muscle degeneration—the hallmark of ALS—in six patients. There has been “no significant disease progression” in these patients, says American Neurological Association president Eva Feldman. This is rare, says Feldman, who is the study’s principle investigator, and Director of Research of the ALS Clinic at the University of Michigan Health System.

    She adds: “Being a Michigan wolverine, I’ll use an analogy. It’s as rare as a red wolf. And that is very rare.”

    Before surgery, all six of the extraordinary responders had disease only two years along. All of those also lacked the speaking and swallowing complications of “bulbar ALS.” Nine other patients, eight of whom either had bulbar ALS, or advanced disease of five-plus years, did not respond. So the improvements only appear to occur in patients in an earlier phase of the disease.

    But the FDA strictly curtailed the number of stem cells allowed at that stage. Millions more cells will soon be given to new patients.

    Neuralstem’s Spinal Cord Delivery Platform “floats” on patients’s backs during operations, keeping cell-injecting cannulas from tearing spinal cords.

    Feldman was interviewed after presenting the new data on May 17 to researchers at the Romanian Neurological Society Congress. The Phase 1 trial, conducted at Emory University, involved the administration of human fetal spinal cord stem cells to the lower (lumbar) spinal region of nine ALS patients; the upper cervical region of three ALS patients; and both regions to three patients.

    In February the trial’s progress persuaded the FDA to greenlight a Phase 2 trial, expected to start this summer. This trial will give 15 new patients millions more cells, and will test for efficacy. The Phase 1 trial, designed simply to test for safety, gave patients only “one tenth the cell doses” the team desires for therapeutic impact, says Garr.

    The first major surprise occurred with the trial’s most impressive responder, Atlanta resident Ted Harada, who couldn’t walk without a cane before receiving one million cells, 500,000 on either side of his lower spine. Within months, in March 2011, he had abandoned the cane and participated in a 2.5 mile walkathon, actions considered unprecedented in medical circles. (Notes Feldman: “That’s an understatement.”) In August 2012, Harada became the last of three patients to receive a second dose of cells—this time, to the upper spinal cord.

    This slide shows (from the top left down) dopaminergic ventral midbrain cells; spinal cord cells; hippocampal cells. The slide to right of each of the first two is an isolation with a particular marker being expressed. The bottom right shows the spinal cord cells are gabaergic. The spinal cord cell above is a motor neuron.

    Harada directed the attention of the general public to the trial. But the medical establishment was already demonstrating “substantial interest,” Feldman says. This was heightened after early results were published in the journal Stem Cells.1

    Results continue to hold steady. Says Garr: “No one has ever seen data like this.”

    The cells, injected into one or both sides of the lower (lumbar) spinal cord of the patients in the first part of the Phase 1 trial, appear to have survived in the six responding patients long enough to pump out therapeutic doses of neurotrophins, natural chemicals protecting neurons from further degeneration. But autopsies reveal the stem cells also seem to be differentiating into neurons, and hooking up synaptically, as they did in animal models,2 a significant development.

    “The cells mature and form synaptic connections on diseased motor neurons in the spinal cords of ALS animal models. It is remarkable actually,” says Feldman. “No small molecule drug has proved effective in man, and neither has any small molecule drug shown the histological and physiological preservation of function that stem cells have in animal models of ALS.”

    The manuscript on the final results will be submitted to a journal soon, she says.

    In this summer’s Phase 2 trial, Feldman will give millions more cells to 15 more ALS patients. Most will receive the cells in the upper spine, although three will receive cells in both the upper and lower spine. The upper spine is critical. Most ALS patients die when the disease attacks muscles controlling their lungs.

    A neural stem cell derived neuron with axons flailing. The dots are synapses where it is connecting to other neurons.
    Neuralstem’s fetal cells are unlike embryonic stem cells in that they are more differentiated (mature), yet still robust: controllable yet potent. They are unlike fully adult neural stem cells in that they are younger, and possess fewer mutations.

    Neuralstem has many different neural stem cell lines, and has created devices with which to deliver them. In March, the company signed a licensing deal giving Cedars-Sinai Medical Center in Los Angeles rights to use Neuralstem’s platform and floating cannula in its research into spinal cord injuries and chronic diseases.

    In January, Neuralstem received FDA approval to try the same spinal cord cells on patients with chronic spinal cord injury leading to complete paralysis. The cells will be given one-to-two years post-injury. This week, University of San Diego neurologist Martin Marsala reported Neuralstem’s cells significantly alleviated some motor and sensory damage in rats with acute spinal cord injury.3

    Using its cells to screen for drugs, the company developed four neurogenic small molecule compounds for the treatment of major depressive disorder. An FDA-approved Phase 1b safety trial of one drug is ongoing.

    A stroke clinical trial using Neuralstem cells will soon be launched in China.

    “We’re there and it’s real,” says Garr of the stem cell regeneration era.

  2. Hey little brother, sittin under a big live oak we’re crown cleaning thinking about how hot it is. Would be complaining but my thoughts went to you. Odd how things work. Let me share my thoughts. For a couple of years i felt a little unfortunate about failed, or at least postponed retirement plans. Today i put on that saddle you gifted me and got in this tree to help finish it up. I got to thinking how blessed i am at 61 to be able to even climb at all. Better yet i’m surely much more capable and safer than i was at half my age, aside from physical strength. You being who you are made this possible for sure. Watching your teaching techniques and passion for better tree climbing renewed my interest. Also, your loss of mobility has given me an unmeasurable thankfulness for the ability to even stand when i wake up each morning much less being able to climb a tree. Know that i give GOD above thanks for that blessing and that you were somehowe the vehicle to deliver it. Call me crazy but i still beleive for your 100 percent recovery. Why not you?!

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