Archives for category: biotherapy

In some ways, a lasting traumatic brain injury (TBI) can be the worst kind of injury a person can endure in life. A TBI occurs when the brain is injured by force, and depending on the area affected, an individual is left with difficulty functioning and interacting with their environment. Our movement, sensation, communication, memory and learning is processed and controlled by the brain. When these functions are damaged, the interaction with our world is damaged as well.

Treating traumatic brain injuries may be one of the most emotionally and professionally difficult tasks. In an instant, the development of a person’s years of learning and communication can be erased from an injury such as a blow to the head, possibly leaving someone with the mental capacity and behavior of a toddler. Someone with a traumatic brain injury is often easily confused, unpredictable with their speech and actions, and occasionally aggressive as their frustration with communicating increases and appropriateness is inhibited. I recall treating an older gentleman who was the victim of violence, and just asking him to turn his head caused nausea, visual difficulty, and confusion in following just that simple command.

TBI’s can be divided into three main categories: mild, moderate, and severe. A mild injury often encompasses the kind of TBI that many people experience during their lifetime: a short-lasting concussion with possible loss of consciousness of up to a few minutes. Symptoms are often absent or mild, with some resulting nausea or headache. In a moderate injury, the force of the injury is greater and someone can be unconscious for up to 15 minutes with more lasting symptoms.

The third category is severe TBI’s, which can result from an event such as gunshot wound or the force of an explosion. Severe TBI’s cause permanent damage to the brain and leave lasting effects from which a person generally does not every fully recover. These chronic and lasting effects greatly affect a person’s ability to move, work, communicate with people, and function in society.

Until recently, treatment for people with chronic TBI’s was limited, but there is now hope for progress. A recent study by Chou et al introduced ISRIB, a drug tested in UCSF’s lab which was able to reverse the effects of a TBI in mice. This was done by inhibiting a stress response in the brain commonly associated with TBI. The integrated stress response has been shown to be chronically activated in someone with a TBI, affecting the hippocampus’ ability to store memory and influence healthy cognition. In addition, the drug was able to assist in synthesis of proteins which contribute to learning, in a process called Long Term Potentiation (LTP).

Because the effects of a severe traumatic brain injury can last for months or years before improving, results of treatment for TBI are often slow and inconsistent. Generally, there is no effective protocol treating chronic TBI’s because they are so varied in origin and presentation. This is why the breakthrough from UCSF is so impactive. To possibly reverse the effects of brain damage offers extensive hope and potential for TBI survivors, their families, and their care team.

The absolutely amazing aspect of ISRIB is that it affects chronic effects of TBI. Chronic effects of an injury are very difficult to reverse as the system has often acclimated to its chronic state, making the effects more stable and difficult to change. It is incredible that a drug has been developed to not only inhibit the pathway of a TBI, but reverse its deleterious and long-lasting effects. The potential implications of this medications are massive, possibly allowing people with TBI’s to not only restore memory but continue learning.

Thus far ISRIB has only been tested in mice, and the next phase is move it forward for human testing. ISRIB was licensed in 2015 to Calico, a California-based company which owns rights to discoveries in Dr. Walter’s biochemistry lab at UCSF.

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Regenerative medicine using biotherapy and bioprinting is providing much hope for previously irreversible conditions such as burns, muscle damage, and cancer. Cells and cellular environments are extremely difficult to reproduce once they are damaged, and much of regenerative medicine focuses on how to repair what our bodies originally made so easily.  3D cell production, versus 2D cell production, mimics the organic environment of our bodies to produce cells. In biotherapy, living organisms are used as the starter in this process.

The complexity in the specificity of our cells is part of why it is so difficult to reverse cell damage. Thus, stem cells are valuable biological material due to their ability to differentiate into any type of cell based on their environment and genetic factors. A stem cell starts out as a blank slate, and by receiving environmental and genetic signals, can become virtually anything in the human body, from a kidney to a blood cell to a muscle in the leg.

Placental stem cells are organically derived and the natural byproduct during a birth. Instead of being discarded, they can provide a very important product for placental cell therapy, which helps direct cells toward regeneration and promotes healing. In biotherapy, these placental stem cells can be very valuable for the cell production process.

Pluristem, a company quickly gaining international presence, produces 3D cultured placental stem cell therapies for various conditions. The company uses a 3D platform to produce their line of PLX products, mimicking the environment of the human body for cell production. This cell therapy is developed to provide cell therapy which is easy to use and does not require genetic or tissue matching. Once the therapy is administered, it promotes the body to heal itself in the target area.

Pluristem products provided regenerative therapy for a variety previously potentially irreversible conditions. Among these is acute radiation syndrome (ARS), which involves irreversible damage to organs and bone marrrow from radiation exposure. Pluristem also aims to provide therapy for vascular conditions such as critical limb ischemia, intermittent claudication, and pulmonary arterial hypertension, all which are dangerous and can lead to decreased life span or surgery.

Pluristem is currently in its clinical trial phase, with collaborations with several universities and industry partners, including the NIH.

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